Mixed Topics

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

jremaly@mdedge.com

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

jremaly@mdedge.com

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

jremaly@mdedge.com

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

A version of this article first appeared on Medscape.com.

New models are needed for delivering long-term care (LTC) that are home-based, cost-effective, and appropriate for older adults with a range of care needs.^1,2 In fiscal year (FY) 2015, the US Department of Veterans Affairs (VA) spent $7.4 billion on LTC, accounting for 13% of total VA health care spending. Overall, 71% of LTC spending in FY 2015 was allocated to institutional care.³ Beyond cost, 95% of older adults prefer to remain in community rather than institutional LTC settings, such as nursing homes.⁴ The COVID-19 pandemic created additional concerns related to the spread of infectious disease, with > 37% of COVID-19 deaths in the United States occurring in nursing homes irrespective of facility quality.^5,6

One community-based LTC alternative developed within the VA is the Medical Foster Home (MFH) program. The MFH program is an adult foster care program in which veterans who are unable to live independently receive round-the-clock care in the home of a community-based caregiver.⁷ MFH caregivers usually have previous experience caring for family, working in a nursing home, or working as a caregiver in another capacity. These caregivers are responsible for providing 24-hour supervision and support to residents in their MFH and can care for up to 3 adults. In the MFH program, VA home-based primary care (HBPC) teams composed of physicians, registered nurses, physical and occupational therapists, social workers, pharmacists, dieticians, and psychologists, provide primary care for MFH veterans and oversee care in the caregiver’s home.

The goal of the VA HBPC program is to improve veterans’ access to medical care and shift LTC services from institutional to noninstitutional settings by providing in-home care for those who are too sick or disabled to go to a clinic for care. On average, veterans pay the MFH caregiver $2,500 out-of-pocket per month for their care.⁸ In 2016, there were 992 veterans residing in MFHs across the country.⁹ Since MFH program implementation expanded nationwide in 2008, more than 4,000 veterans have resided in MFHs in 45 states and territories.¹⁰

The VA is required to pay for nursing home care for veterans who have a qualifying VA service-connected disability or who meet a specific threshold of disability.¹¹ Currently, the VA is not authorized to pay for MFH care for veterans who meet the eligibility criteria for VA-paid nursing home care. Over the past decade, the VA has introduced and expanded several initiatives and programs to help veterans who require LTC remain in their homes and communities. These include but are not limited to the Veteran Directed Care program, the Choose Home Initiative, and the Caregiver Support Program.^12-14 Additionally, attempts have been made to pass legislation to authorize the VA to pay for MFH for veterans’ care whose military benefits include coverage for nursing home care.¹⁵ This legislation and VA initiatives are clear signs that the VA is committed to supporting programs such as the MFH program. Given this commitment, demand for the MFH program will likely increase.

Therefore, VA practitioners need to better identify which veterans are currently in the MFH program. While veterans are expected to need nursing home level care to qualify for MFH enrollment, little has been published about the physical and mental health care needs of veterans currently receiving MFH care. One previous study compared the demographics, diagnostic characteristics, and care utilization of MFH veterans with that of veterans receiving LTC in VA community living centers (CLCs), and found that veterans in MFHs had similar levels of frailty and comorbidity and had a higher mean age when compared with veterans in CLCs.¹⁶

Our study assessed a sample of veterans living in MFHs and describes these veterans’ clinical and functional characteristics. We used the Minimum Data Set 3.0 (MDS) to complete the assessments to allow comparisons with other populations residing in long-term care.^17,18 While MDS assessments are required for Medicare/Medicaid-certified nursing home residents and for residents in VA CLCs, this study was the first attempt to perform in-home MDS data assessments in MFHs. This collection of descriptive clinical data is an important first step in providing VA practitioners with information about the characteristics of veterans currently cared for in MFHs and policymakers with data to think critically about which veterans are willing to pay for the MFH program.

Methods

This study was part of a larger research project assessing the impact of the MFH program on veterans’ outcomes and health care spending as well as factors influencing program growth.^{7,9,10,16,19-23} We report on the characteristics of veterans staying in MFHs, using data from the MDS, including a clinical assessment of patients’ cognitive, function, and health care–related needs, collected from participants recruited for this study.

Five research nurses were trained to administer the MDS assessment to veterans in MFHs. Data were collected between April 2014 and December 2015 from veterans at MFH sites associated with 4 urban VA medical centers in 4 different Veterans Integrated Service Networks (58 total homes). While the VA medical centers (VAMCs)were urban, many of the MFHs were in rural areas, given that MFHs can be up to 50 miles from the associated VAMC. We selected MFH sites for this study based on MFH program veteran census. Specifically, we identified MFH sites with high veteran enrollment to ensure we would have a sufficiently large sample for participant recruitment.

Veterans who had resided in an MFH for at least 90 days were eligible to participate. Of the 155 veterans mailed a letter of invitation to participate, 92 (59%) completed the in-home MDS assessment. Reasons for not participating included: 13 veterans died prior to data collection, 18 veterans declined to participate, 18 family members or legal guardians of cognitively impaired veterans did not want the veteran to participate, and 14 veterans left the MFH program or were hospitalized at the time of data collection.

Family members and legal guardians who declined participation on behalf of a veteran reported that they felt the veteran was too frail to participate or that participating would be an added burden on the veteran. Based on the census of veterans residing in all MFHs nationally in November 2015 (N = 972), 9.5% of MFH veterans were included in this study.⁷This study was approved by the VA Central Institutional Review Board (CIRB #12–31), in addition to the local VA research and development review boards where MFH MDS assessments were collected.

Assessment Instrument and Variables

The MDS 3.0 assesses numerous aspects of clinical and functional status. Several resident-level characteristics from the MDS 3.0 were included in this study. The Cognitive Function Scale (CFS) was used to categorize cognitive function. The CFS is a categorical variable that is created from MDS 3.0 data. The CFS integrates self- and staff-reported data to classify individuals as cognitively intact, mildly impaired, moderately impaired, or severely impaired based on respondents’ Brief Interview for Mental Status (BIMS) assessment or staff-reported cognitive function collected as part of the MDS 3.0.²⁴ We explored depression by calculating a mean summary severity score for all respondents from the Patient Health Questionnaire-9 item interview (PHQ-9).²⁵ PHQ-9 summary scores range from 0 to 27, with mean scores of ≤ 4 indicating no or minimal depression, and higher scores corresponding to more severe depression as scores increase. For respondents who were unable to complete the PHQ-9, we calculated mean PHQ Observational Version (PHQ-9-OV) scores.

We included 2 variables to characterize behaviors: wandering frequency and presence and frequency of aggressive behaviors. We summarized aggressive behaviors using the Aggressive and Reactive Behavior Scale, which characterizes whether a resident has none, mild, moderate, or severe behavioral symptoms based on the presence and frequency of physical and verbal behaviors and resistance to care.^26,27 We included items that described pain, number of falls since admission or prior assessment, degree of urinary and bowel continence (always continent vs not always continent) and mobility device use to describe respondents’ health conditions and functional status. To characterize pain, we used veteran’s self-reported frequency and intensity of pain experienced in the prior 5 days and classified the experienced pain as none, mild, moderate, or severe. Finally, demographic characteristics included age and gender.

To determine functional status, we included measures of needing help to perform activities of daily living (ADLs). The MDS allows us to understand functional status ranging from ADLs lost early in the trajectory of functional decline (ie, bathing, hygiene) to those lost in the middle (ie, walking, dressing, toileting, transferring) to those lost late in the trajectory of functional decline (ie, bed mobility and eating).^28,29 To assess MFH veterans’ independence in mobility, we considered the veteran’s ability to walk without supervision or assistance in the hallway outside of their room, ability to move between their room and hallway, and ability to move throughout the house. Mobility includes use of an assistive device such as a cane, walker, or wheelchair if the veteran can use it without assistance. We summarized dependency in ADLs, using a combined score of dependence in bed mobility, transfer, locomotion on unit, dressing, eating, toilet use, and personal hygiene that ranges from 0 (independent) to 28 (completely dependent).³⁰ Additionally, we created 3-category variables to indicate the degree of dependence in performing ADLs (independent, supervision or assistance, and completely dependent).

Finally, we included diagnoses identified as active to explore differences in neurologic, mood, psychiatric, and chronic disease morbidity. In the MDS 3.0 assessment, an active diagnosis is defined as a diagnosis documented by a licensed independent practitioner in the prior 60 days that has affected the resident or their care in the prior 7 days.

Analysis

We conducted statistical analyses using Stata MP version 15.1 (StataCorp). We summarized demographic characteristics, cognitive function scores, depression scores, pain status, behavioral symptoms, incidence of falls, degree of continence, functional status, and comorbidities, using means and standard deviations for continuous variables and frequencies and proportions for categorical variables.

Results

Of the 92 MFH veterans in our sample, 85% were male and 83% were aged ≥ 65 years (Table 1). Veterans had an average length of stay of 927 days at the time of MDS assessment. More than half (55%) of MFH veterans had cognitive impairment (ranging from mild to severe). The mean (SD) depression score was 3.3 (3.9), indicating minimal depression. For veterans who could not complete the depression questionnaire, the mean (SD) staff-assessed depression score was 5.9 (5.5), suggesting mild depression. Overall, 22% of the sample had aggressive behaviors but only 7 were noted to be severe. Few residents had caregiver-reported wandering. Self-reported pain intensity indicated that 45% of the sample had mild, moderate, or severe pain. While more than half the cohort had complete bowel continence (53%), only 36% had complete urinary continence. Use of mobility devices was common, with 56% of residents using a wheelchair, 42% using a walker, and 14% using a cane. One-fourth of veterans had fallen at least once since admission to the MFH.

Of the 11 ADLs assessed, the percentage of MFH veterans requiring assistance with early and mid-loss ADLs ranged from 63% for transferring to 84% for bathing (Table 2). Even for the late-loss ADL of eating, 57% of the MFH cohort required assistance. Overall, MFH veterans had an average ADL dependency score of 11.

Discussion

In this study, we describe the characteristics of veterans receiving LTC in a sample of MFHs. This is the first study to assess veteran health and function across a group of MFHs. To help provide context for the description of MFH residents, we compared demographic characteristics, cognitive impairment, depression, pain, behaviors, functional status, and morbidity of veterans in the MFH program to long-stay residents in community nursing homes (eAppendix 1-3 available at doi:10.12788/fp.0102). A comparison with this reference population suggests that these MFH and nursing home cohorts are similar in terms of age, wandering behavior, incidence of falls, and prevalence of neurologic, psychiatric, and chronic diseases. Compared with nursing home residents, veterans in the MFH cohort had slightly higher mood symptom scores, were more likely to display aggressive behavior, and were more likely to report experiencing moderate and severe pain.

Additionally, MFH veterans displayed a lower level of cognitive impairment, fewer functional impairments, measured by the ADL dependency score, and were less likely to be bowel or bladder incontinent. Despite an overall lower ADL dependency score, a similar proportion of MFH veterans and nursing home residents were totally dependent in performing 7 of 11 ADLs and a higher proportion of MFH veterans were completely dependent for toileting (22% long-stay nursing home vs 31% MFH). The only ADLs for which there was a higher proportion of long-stay nursing home residents who were totally dependent compared with MFH residents were walking in room (54% long-stay nursing home vs 38% MFH), walking in the corridor (57% long-stay nursing home vs 33% MFH), and locomotion off the unit (36% long-stay nursing home vs 22% MFH).

While the rates of total ADL dependence among veterans in MFHs suggest that MFHs are providing care to a subset of veterans with high levels of functional impairment and care needs, MFHs are also providing care to veterans who are more independent in performing ADLs and who resemble low-care nursing home residents. A low-care nursing home resident is broadly defined as an one who does not need assistance performing late-loss ADLs (bed mobility, transferring, toileting, and eating) and who does not have the Resource Utilization Group classification of special rehab or clinically complex.^31,32 Due to their overall higher functional capacity, low-care residents, even those with chronic medical care needs, may be more appropriately cared for in less intensive care settings than in nursing homes. About 5% to 30% of long-stay nursing home residents can be classified as low care.^31,33-37 Additionally, a majority of newly admitted nursing home patients report a preference for or support community discharge rather than long-stay nursing home care, suggesting that many nursing home residents have the potential and desire to transition to a community-based setting.³³

Based on the prevalence of veterans in our sample who are similar to low-care nursing home residents and the national focus on shifting LTC to community-based settings, MFHs may be an ideal setting for both low-care nursing home residents and those seeking community-based alternatives to traditional, institutionalized LTC. Additionally, given that we observed greater behavioral and pain needs and similar rates of comorbidities in MFH veterans relative to long-stay nursing home residents, our results indicate that MFHs also have the capacity to care for veterans with higher care needs who desire community-based LTC.

Previous research identified barriers to program MFH growth that may contribute to referral of veterans with fewer ADL dependencies compared with long-stay nursing home residents. A key barrier to MFH referral is that nursing home referral requires selection of a home, whereas MFH referral involves matching veterans with appropriate caregivers, which requires time to align the veteran’s needs with the right caregiver in the right home.⁷ Given the rigors of finding a match, VA staff who refer veterans may preferentially refer veterans with greater ADL impairments to nursing homes, assuming that higher levels of care needs will complicate the matching process and reserve MFH referral for only the highest functioning candidates.¹⁹ However, the ADL data presented here indicate that many MFH residents with significant levels of ADL dependence are living in MFHs. Meeting the care needs of those who have higher ADL dependencies is possible because MFH coordinators and HBPC providers deliver individual, ongoing education to MFH caregivers about caring for MFH veterans and provide available resources needed to safely care for MFH veterans across the spectrum of ADL dependency.⁷

Veterans with higher levels of functional dependence may also be referred to nursing homes rather than to MFHs because of payment issues. Independent of the VA, veterans or their families negotiate a contract with their caregiver to pay out-of-pocket for MFH caregiving as well as room and board. Particularly for veterans who have military benefits to cover nursing home care costs, the out-of-pocket payment for veterans with high degrees of functional dependence increase as needs increase. These out-of-pocket payments may serve as a barrier to MFH enrollment. The proposed Long-Term Care Veterans Choice Act, which would allow the VA to pay for MFH care for eligible veterans may address this barrier.¹⁵

Another possible explanation for the higher rates of functional independence in the MFH cohort is that veterans with functional impairment are not being referred to MFHs. A previous study of the MFH program found that health care providers were often unaware of the program and as a result did not refer eligible veterans to this alternative LTC option.⁷ The changes proposed by the Long-Term Care Veterans Choice Act may result in an increase in demand in MFH care and thus increase awareness of the program among VA physicians.¹⁵

Limitations

There are several potential limitations in this study. First, there are limits to the generalizability of the MFH sample given that the sample of veterans was not randomly selected and that weights were not applied to account for nonresponse bias. Second, charting requirements in MFHs are less intensive compared with nursing home tracking. While the training for research nurses on how to conduct MDS assessments in MFHs was designed to simulate the process in nursing homes, MDS data were likely impacted by differences in charting practices. In addition, MFH caregivers may report certain items, such as aggressive behaviors, more often because they observe MFH veterans round-the-clock compared with NH caregivers who work in shifts and have a lower caregiver to resident ratio. The current data suggest differences in prevalence of behavioral symptoms.

Future studies should examine whether this reflects differences in the populations served or differences in how MFH caregivers track and manage behavioral symptoms. Third, this study was conducted at only MFH sites associated with 4 VAMCs, thus our findings may not be generalizable to veterans in other areas. Finally, there may be differences in the veterans who agreed to participate in the study compared with those who declined to participate. For example, it is possible that the eligible MFH veterans who declined to participate in this study were more functionally impaired than those who did participate. More than one-third (39%) of the family members of cognitively impaired MFH veterans who did not participate cited concerns about the veteran’s frailty as a primary reason for declining to participate. Consequently, the high level of functional status among veterans included in this study compared to nursing home residents may be in part a result of selection bias from more ADL-impaired veterans declining to participate in the study.

Conclusions

Although the MFH program has provided LTC nationally to veterans for nearly 2 decades, this study is the first to administer in-home MDS assessments to veterans in MFHs, allowing for a detailed description of cognitive, functional, and behavioral characteristics of MFH residents. In this study, we found that veterans currently receiving care in MFHs have a wide range of care needs. Our findings indicate that MFHs are caring for some veterans with high functional impairment as well as those who are completely independent in performing ADLs.

Moreover, these results are a preliminary attempt to assist VA health care providers in determining which veterans can be cared for in an MFH such that they can make informed referrals to this alternative LTC setting. To improve the generalizability of these findings, future studies should collect MDS 3.0 assessments longitudinally from a representative sample of veterans in MFHs. Further research is needed to explore how VA providers make the decision to refer a veteran to an MFH compared to a nursing home. Additionally, the percentage of veterans in this study who reported experiencing pain may indicate the need to identify innovative, integrated pain management programs for home settings.

New models are needed for delivering long-term care (LTC) that are home-based, cost-effective, and appropriate for older adults with a range of care needs.^1,2 In fiscal year (FY) 2015, the US Department of Veterans Affairs (VA) spent $7.4 billion on LTC, accounting for 13% of total VA health care spending. Overall, 71% of LTC spending in FY 2015 was allocated to institutional care.³ Beyond cost, 95% of older adults prefer to remain in community rather than institutional LTC settings, such as nursing homes.⁴ The COVID-19 pandemic created additional concerns related to the spread of infectious disease, with > 37% of COVID-19 deaths in the United States occurring in nursing homes irrespective of facility quality.^5,6

One community-based LTC alternative developed within the VA is the Medical Foster Home (MFH) program. The MFH program is an adult foster care program in which veterans who are unable to live independently receive round-the-clock care in the home of a community-based caregiver.⁷ MFH caregivers usually have previous experience caring for family, working in a nursing home, or working as a caregiver in another capacity. These caregivers are responsible for providing 24-hour supervision and support to residents in their MFH and can care for up to 3 adults. In the MFH program, VA home-based primary care (HBPC) teams composed of physicians, registered nurses, physical and occupational therapists, social workers, pharmacists, dieticians, and psychologists, provide primary care for MFH veterans and oversee care in the caregiver’s home.

The goal of the VA HBPC program is to improve veterans’ access to medical care and shift LTC services from institutional to noninstitutional settings by providing in-home care for those who are too sick or disabled to go to a clinic for care. On average, veterans pay the MFH caregiver $2,500 out-of-pocket per month for their care.⁸ In 2016, there were 992 veterans residing in MFHs across the country.⁹ Since MFH program implementation expanded nationwide in 2008, more than 4,000 veterans have resided in MFHs in 45 states and territories.¹⁰

The VA is required to pay for nursing home care for veterans who have a qualifying VA service-connected disability or who meet a specific threshold of disability.¹¹ Currently, the VA is not authorized to pay for MFH care for veterans who meet the eligibility criteria for VA-paid nursing home care. Over the past decade, the VA has introduced and expanded several initiatives and programs to help veterans who require LTC remain in their homes and communities. These include but are not limited to the Veteran Directed Care program, the Choose Home Initiative, and the Caregiver Support Program.^12-14 Additionally, attempts have been made to pass legislation to authorize the VA to pay for MFH for veterans’ care whose military benefits include coverage for nursing home care.¹⁵ This legislation and VA initiatives are clear signs that the VA is committed to supporting programs such as the MFH program. Given this commitment, demand for the MFH program will likely increase.

Therefore, VA practitioners need to better identify which veterans are currently in the MFH program. While veterans are expected to need nursing home level care to qualify for MFH enrollment, little has been published about the physical and mental health care needs of veterans currently receiving MFH care. One previous study compared the demographics, diagnostic characteristics, and care utilization of MFH veterans with that of veterans receiving LTC in VA community living centers (CLCs), and found that veterans in MFHs had similar levels of frailty and comorbidity and had a higher mean age when compared with veterans in CLCs.¹⁶

Our study assessed a sample of veterans living in MFHs and describes these veterans’ clinical and functional characteristics. We used the Minimum Data Set 3.0 (MDS) to complete the assessments to allow comparisons with other populations residing in long-term care.^17,18 While MDS assessments are required for Medicare/Medicaid-certified nursing home residents and for residents in VA CLCs, this study was the first attempt to perform in-home MDS data assessments in MFHs. This collection of descriptive clinical data is an important first step in providing VA practitioners with information about the characteristics of veterans currently cared for in MFHs and policymakers with data to think critically about which veterans are willing to pay for the MFH program.

Methods

This study was part of a larger research project assessing the impact of the MFH program on veterans’ outcomes and health care spending as well as factors influencing program growth.^{7,9,10,16,19-23} We report on the characteristics of veterans staying in MFHs, using data from the MDS, including a clinical assessment of patients’ cognitive, function, and health care–related needs, collected from participants recruited for this study.

Five research nurses were trained to administer the MDS assessment to veterans in MFHs. Data were collected between April 2014 and December 2015 from veterans at MFH sites associated with 4 urban VA medical centers in 4 different Veterans Integrated Service Networks (58 total homes). While the VA medical centers (VAMCs)were urban, many of the MFHs were in rural areas, given that MFHs can be up to 50 miles from the associated VAMC. We selected MFH sites for this study based on MFH program veteran census. Specifically, we identified MFH sites with high veteran enrollment to ensure we would have a sufficiently large sample for participant recruitment.

Veterans who had resided in an MFH for at least 90 days were eligible to participate. Of the 155 veterans mailed a letter of invitation to participate, 92 (59%) completed the in-home MDS assessment. Reasons for not participating included: 13 veterans died prior to data collection, 18 veterans declined to participate, 18 family members or legal guardians of cognitively impaired veterans did not want the veteran to participate, and 14 veterans left the MFH program or were hospitalized at the time of data collection.

Family members and legal guardians who declined participation on behalf of a veteran reported that they felt the veteran was too frail to participate or that participating would be an added burden on the veteran. Based on the census of veterans residing in all MFHs nationally in November 2015 (N = 972), 9.5% of MFH veterans were included in this study.⁷This study was approved by the VA Central Institutional Review Board (CIRB #12–31), in addition to the local VA research and development review boards where MFH MDS assessments were collected.

Assessment Instrument and Variables

The MDS 3.0 assesses numerous aspects of clinical and functional status. Several resident-level characteristics from the MDS 3.0 were included in this study. The Cognitive Function Scale (CFS) was used to categorize cognitive function. The CFS is a categorical variable that is created from MDS 3.0 data. The CFS integrates self- and staff-reported data to classify individuals as cognitively intact, mildly impaired, moderately impaired, or severely impaired based on respondents’ Brief Interview for Mental Status (BIMS) assessment or staff-reported cognitive function collected as part of the MDS 3.0.²⁴ We explored depression by calculating a mean summary severity score for all respondents from the Patient Health Questionnaire-9 item interview (PHQ-9).²⁵ PHQ-9 summary scores range from 0 to 27, with mean scores of ≤ 4 indicating no or minimal depression, and higher scores corresponding to more severe depression as scores increase. For respondents who were unable to complete the PHQ-9, we calculated mean PHQ Observational Version (PHQ-9-OV) scores.

We included 2 variables to characterize behaviors: wandering frequency and presence and frequency of aggressive behaviors. We summarized aggressive behaviors using the Aggressive and Reactive Behavior Scale, which characterizes whether a resident has none, mild, moderate, or severe behavioral symptoms based on the presence and frequency of physical and verbal behaviors and resistance to care.^26,27 We included items that described pain, number of falls since admission or prior assessment, degree of urinary and bowel continence (always continent vs not always continent) and mobility device use to describe respondents’ health conditions and functional status. To characterize pain, we used veteran’s self-reported frequency and intensity of pain experienced in the prior 5 days and classified the experienced pain as none, mild, moderate, or severe. Finally, demographic characteristics included age and gender.

To determine functional status, we included measures of needing help to perform activities of daily living (ADLs). The MDS allows us to understand functional status ranging from ADLs lost early in the trajectory of functional decline (ie, bathing, hygiene) to those lost in the middle (ie, walking, dressing, toileting, transferring) to those lost late in the trajectory of functional decline (ie, bed mobility and eating).^28,29 To assess MFH veterans’ independence in mobility, we considered the veteran’s ability to walk without supervision or assistance in the hallway outside of their room, ability to move between their room and hallway, and ability to move throughout the house. Mobility includes use of an assistive device such as a cane, walker, or wheelchair if the veteran can use it without assistance. We summarized dependency in ADLs, using a combined score of dependence in bed mobility, transfer, locomotion on unit, dressing, eating, toilet use, and personal hygiene that ranges from 0 (independent) to 28 (completely dependent).³⁰ Additionally, we created 3-category variables to indicate the degree of dependence in performing ADLs (independent, supervision or assistance, and completely dependent).

Finally, we included diagnoses identified as active to explore differences in neurologic, mood, psychiatric, and chronic disease morbidity. In the MDS 3.0 assessment, an active diagnosis is defined as a diagnosis documented by a licensed independent practitioner in the prior 60 days that has affected the resident or their care in the prior 7 days.

Analysis

We conducted statistical analyses using Stata MP version 15.1 (StataCorp). We summarized demographic characteristics, cognitive function scores, depression scores, pain status, behavioral symptoms, incidence of falls, degree of continence, functional status, and comorbidities, using means and standard deviations for continuous variables and frequencies and proportions for categorical variables.

Results

Of the 92 MFH veterans in our sample, 85% were male and 83% were aged ≥ 65 years (Table 1). Veterans had an average length of stay of 927 days at the time of MDS assessment. More than half (55%) of MFH veterans had cognitive impairment (ranging from mild to severe). The mean (SD) depression score was 3.3 (3.9), indicating minimal depression. For veterans who could not complete the depression questionnaire, the mean (SD) staff-assessed depression score was 5.9 (5.5), suggesting mild depression. Overall, 22% of the sample had aggressive behaviors but only 7 were noted to be severe. Few residents had caregiver-reported wandering. Self-reported pain intensity indicated that 45% of the sample had mild, moderate, or severe pain. While more than half the cohort had complete bowel continence (53%), only 36% had complete urinary continence. Use of mobility devices was common, with 56% of residents using a wheelchair, 42% using a walker, and 14% using a cane. One-fourth of veterans had fallen at least once since admission to the MFH.

Of the 11 ADLs assessed, the percentage of MFH veterans requiring assistance with early and mid-loss ADLs ranged from 63% for transferring to 84% for bathing (Table 2). Even for the late-loss ADL of eating, 57% of the MFH cohort required assistance. Overall, MFH veterans had an average ADL dependency score of 11.

Discussion

In this study, we describe the characteristics of veterans receiving LTC in a sample of MFHs. This is the first study to assess veteran health and function across a group of MFHs. To help provide context for the description of MFH residents, we compared demographic characteristics, cognitive impairment, depression, pain, behaviors, functional status, and morbidity of veterans in the MFH program to long-stay residents in community nursing homes (eAppendix 1-3 available at doi:10.12788/fp.0102). A comparison with this reference population suggests that these MFH and nursing home cohorts are similar in terms of age, wandering behavior, incidence of falls, and prevalence of neurologic, psychiatric, and chronic diseases. Compared with nursing home residents, veterans in the MFH cohort had slightly higher mood symptom scores, were more likely to display aggressive behavior, and were more likely to report experiencing moderate and severe pain.

Additionally, MFH veterans displayed a lower level of cognitive impairment, fewer functional impairments, measured by the ADL dependency score, and were less likely to be bowel or bladder incontinent. Despite an overall lower ADL dependency score, a similar proportion of MFH veterans and nursing home residents were totally dependent in performing 7 of 11 ADLs and a higher proportion of MFH veterans were completely dependent for toileting (22% long-stay nursing home vs 31% MFH). The only ADLs for which there was a higher proportion of long-stay nursing home residents who were totally dependent compared with MFH residents were walking in room (54% long-stay nursing home vs 38% MFH), walking in the corridor (57% long-stay nursing home vs 33% MFH), and locomotion off the unit (36% long-stay nursing home vs 22% MFH).

While the rates of total ADL dependence among veterans in MFHs suggest that MFHs are providing care to a subset of veterans with high levels of functional impairment and care needs, MFHs are also providing care to veterans who are more independent in performing ADLs and who resemble low-care nursing home residents. A low-care nursing home resident is broadly defined as an one who does not need assistance performing late-loss ADLs (bed mobility, transferring, toileting, and eating) and who does not have the Resource Utilization Group classification of special rehab or clinically complex.^31,32 Due to their overall higher functional capacity, low-care residents, even those with chronic medical care needs, may be more appropriately cared for in less intensive care settings than in nursing homes. About 5% to 30% of long-stay nursing home residents can be classified as low care.^31,33-37 Additionally, a majority of newly admitted nursing home patients report a preference for or support community discharge rather than long-stay nursing home care, suggesting that many nursing home residents have the potential and desire to transition to a community-based setting.³³

Based on the prevalence of veterans in our sample who are similar to low-care nursing home residents and the national focus on shifting LTC to community-based settings, MFHs may be an ideal setting for both low-care nursing home residents and those seeking community-based alternatives to traditional, institutionalized LTC. Additionally, given that we observed greater behavioral and pain needs and similar rates of comorbidities in MFH veterans relative to long-stay nursing home residents, our results indicate that MFHs also have the capacity to care for veterans with higher care needs who desire community-based LTC.

Previous research identified barriers to program MFH growth that may contribute to referral of veterans with fewer ADL dependencies compared with long-stay nursing home residents. A key barrier to MFH referral is that nursing home referral requires selection of a home, whereas MFH referral involves matching veterans with appropriate caregivers, which requires time to align the veteran’s needs with the right caregiver in the right home.⁷ Given the rigors of finding a match, VA staff who refer veterans may preferentially refer veterans with greater ADL impairments to nursing homes, assuming that higher levels of care needs will complicate the matching process and reserve MFH referral for only the highest functioning candidates.¹⁹ However, the ADL data presented here indicate that many MFH residents with significant levels of ADL dependence are living in MFHs. Meeting the care needs of those who have higher ADL dependencies is possible because MFH coordinators and HBPC providers deliver individual, ongoing education to MFH caregivers about caring for MFH veterans and provide available resources needed to safely care for MFH veterans across the spectrum of ADL dependency.⁷

Veterans with higher levels of functional dependence may also be referred to nursing homes rather than to MFHs because of payment issues. Independent of the VA, veterans or their families negotiate a contract with their caregiver to pay out-of-pocket for MFH caregiving as well as room and board. Particularly for veterans who have military benefits to cover nursing home care costs, the out-of-pocket payment for veterans with high degrees of functional dependence increase as needs increase. These out-of-pocket payments may serve as a barrier to MFH enrollment. The proposed Long-Term Care Veterans Choice Act, which would allow the VA to pay for MFH care for eligible veterans may address this barrier.¹⁵

Another possible explanation for the higher rates of functional independence in the MFH cohort is that veterans with functional impairment are not being referred to MFHs. A previous study of the MFH program found that health care providers were often unaware of the program and as a result did not refer eligible veterans to this alternative LTC option.⁷ The changes proposed by the Long-Term Care Veterans Choice Act may result in an increase in demand in MFH care and thus increase awareness of the program among VA physicians.¹⁵

Limitations

There are several potential limitations in this study. First, there are limits to the generalizability of the MFH sample given that the sample of veterans was not randomly selected and that weights were not applied to account for nonresponse bias. Second, charting requirements in MFHs are less intensive compared with nursing home tracking. While the training for research nurses on how to conduct MDS assessments in MFHs was designed to simulate the process in nursing homes, MDS data were likely impacted by differences in charting practices. In addition, MFH caregivers may report certain items, such as aggressive behaviors, more often because they observe MFH veterans round-the-clock compared with NH caregivers who work in shifts and have a lower caregiver to resident ratio. The current data suggest differences in prevalence of behavioral symptoms.

Future studies should examine whether this reflects differences in the populations served or differences in how MFH caregivers track and manage behavioral symptoms. Third, this study was conducted at only MFH sites associated with 4 VAMCs, thus our findings may not be generalizable to veterans in other areas. Finally, there may be differences in the veterans who agreed to participate in the study compared with those who declined to participate. For example, it is possible that the eligible MFH veterans who declined to participate in this study were more functionally impaired than those who did participate. More than one-third (39%) of the family members of cognitively impaired MFH veterans who did not participate cited concerns about the veteran’s frailty as a primary reason for declining to participate. Consequently, the high level of functional status among veterans included in this study compared to nursing home residents may be in part a result of selection bias from more ADL-impaired veterans declining to participate in the study.

Conclusions

Although the MFH program has provided LTC nationally to veterans for nearly 2 decades, this study is the first to administer in-home MDS assessments to veterans in MFHs, allowing for a detailed description of cognitive, functional, and behavioral characteristics of MFH residents. In this study, we found that veterans currently receiving care in MFHs have a wide range of care needs. Our findings indicate that MFHs are caring for some veterans with high functional impairment as well as those who are completely independent in performing ADLs.

Moreover, these results are a preliminary attempt to assist VA health care providers in determining which veterans can be cared for in an MFH such that they can make informed referrals to this alternative LTC setting. To improve the generalizability of these findings, future studies should collect MDS 3.0 assessments longitudinally from a representative sample of veterans in MFHs. Further research is needed to explore how VA providers make the decision to refer a veteran to an MFH compared to a nursing home. Additionally, the percentage of veterans in this study who reported experiencing pain may indicate the need to identify innovative, integrated pain management programs for home settings.

New models are needed for delivering long-term care (LTC) that are home-based, cost-effective, and appropriate for older adults with a range of care needs.^1,2 In fiscal year (FY) 2015, the US Department of Veterans Affairs (VA) spent $7.4 billion on LTC, accounting for 13% of total VA health care spending. Overall, 71% of LTC spending in FY 2015 was allocated to institutional care.³ Beyond cost, 95% of older adults prefer to remain in community rather than institutional LTC settings, such as nursing homes.⁴ The COVID-19 pandemic created additional concerns related to the spread of infectious disease, with > 37% of COVID-19 deaths in the United States occurring in nursing homes irrespective of facility quality.^5,6

One community-based LTC alternative developed within the VA is the Medical Foster Home (MFH) program. The MFH program is an adult foster care program in which veterans who are unable to live independently receive round-the-clock care in the home of a community-based caregiver.⁷ MFH caregivers usually have previous experience caring for family, working in a nursing home, or working as a caregiver in another capacity. These caregivers are responsible for providing 24-hour supervision and support to residents in their MFH and can care for up to 3 adults. In the MFH program, VA home-based primary care (HBPC) teams composed of physicians, registered nurses, physical and occupational therapists, social workers, pharmacists, dieticians, and psychologists, provide primary care for MFH veterans and oversee care in the caregiver’s home.

The goal of the VA HBPC program is to improve veterans’ access to medical care and shift LTC services from institutional to noninstitutional settings by providing in-home care for those who are too sick or disabled to go to a clinic for care. On average, veterans pay the MFH caregiver $2,500 out-of-pocket per month for their care.⁸ In 2016, there were 992 veterans residing in MFHs across the country.⁹ Since MFH program implementation expanded nationwide in 2008, more than 4,000 veterans have resided in MFHs in 45 states and territories.¹⁰

The VA is required to pay for nursing home care for veterans who have a qualifying VA service-connected disability or who meet a specific threshold of disability.¹¹ Currently, the VA is not authorized to pay for MFH care for veterans who meet the eligibility criteria for VA-paid nursing home care. Over the past decade, the VA has introduced and expanded several initiatives and programs to help veterans who require LTC remain in their homes and communities. These include but are not limited to the Veteran Directed Care program, the Choose Home Initiative, and the Caregiver Support Program.^12-14 Additionally, attempts have been made to pass legislation to authorize the VA to pay for MFH for veterans’ care whose military benefits include coverage for nursing home care.¹⁵ This legislation and VA initiatives are clear signs that the VA is committed to supporting programs such as the MFH program. Given this commitment, demand for the MFH program will likely increase.

Therefore, VA practitioners need to better identify which veterans are currently in the MFH program. While veterans are expected to need nursing home level care to qualify for MFH enrollment, little has been published about the physical and mental health care needs of veterans currently receiving MFH care. One previous study compared the demographics, diagnostic characteristics, and care utilization of MFH veterans with that of veterans receiving LTC in VA community living centers (CLCs), and found that veterans in MFHs had similar levels of frailty and comorbidity and had a higher mean age when compared with veterans in CLCs.¹⁶

Our study assessed a sample of veterans living in MFHs and describes these veterans’ clinical and functional characteristics. We used the Minimum Data Set 3.0 (MDS) to complete the assessments to allow comparisons with other populations residing in long-term care.^17,18 While MDS assessments are required for Medicare/Medicaid-certified nursing home residents and for residents in VA CLCs, this study was the first attempt to perform in-home MDS data assessments in MFHs. This collection of descriptive clinical data is an important first step in providing VA practitioners with information about the characteristics of veterans currently cared for in MFHs and policymakers with data to think critically about which veterans are willing to pay for the MFH program.

Methods

This study was part of a larger research project assessing the impact of the MFH program on veterans’ outcomes and health care spending as well as factors influencing program growth.^{7,9,10,16,19-23} We report on the characteristics of veterans staying in MFHs, using data from the MDS, including a clinical assessment of patients’ cognitive, function, and health care–related needs, collected from participants recruited for this study.

Five research nurses were trained to administer the MDS assessment to veterans in MFHs. Data were collected between April 2014 and December 2015 from veterans at MFH sites associated with 4 urban VA medical centers in 4 different Veterans Integrated Service Networks (58 total homes). While the VA medical centers (VAMCs)were urban, many of the MFHs were in rural areas, given that MFHs can be up to 50 miles from the associated VAMC. We selected MFH sites for this study based on MFH program veteran census. Specifically, we identified MFH sites with high veteran enrollment to ensure we would have a sufficiently large sample for participant recruitment.

Veterans who had resided in an MFH for at least 90 days were eligible to participate. Of the 155 veterans mailed a letter of invitation to participate, 92 (59%) completed the in-home MDS assessment. Reasons for not participating included: 13 veterans died prior to data collection, 18 veterans declined to participate, 18 family members or legal guardians of cognitively impaired veterans did not want the veteran to participate, and 14 veterans left the MFH program or were hospitalized at the time of data collection.

Family members and legal guardians who declined participation on behalf of a veteran reported that they felt the veteran was too frail to participate or that participating would be an added burden on the veteran. Based on the census of veterans residing in all MFHs nationally in November 2015 (N = 972), 9.5% of MFH veterans were included in this study.⁷This study was approved by the VA Central Institutional Review Board (CIRB #12–31), in addition to the local VA research and development review boards where MFH MDS assessments were collected.

Assessment Instrument and Variables

The MDS 3.0 assesses numerous aspects of clinical and functional status. Several resident-level characteristics from the MDS 3.0 were included in this study. The Cognitive Function Scale (CFS) was used to categorize cognitive function. The CFS is a categorical variable that is created from MDS 3.0 data. The CFS integrates self- and staff-reported data to classify individuals as cognitively intact, mildly impaired, moderately impaired, or severely impaired based on respondents’ Brief Interview for Mental Status (BIMS) assessment or staff-reported cognitive function collected as part of the MDS 3.0.²⁴ We explored depression by calculating a mean summary severity score for all respondents from the Patient Health Questionnaire-9 item interview (PHQ-9).²⁵ PHQ-9 summary scores range from 0 to 27, with mean scores of ≤ 4 indicating no or minimal depression, and higher scores corresponding to more severe depression as scores increase. For respondents who were unable to complete the PHQ-9, we calculated mean PHQ Observational Version (PHQ-9-OV) scores.

We included 2 variables to characterize behaviors: wandering frequency and presence and frequency of aggressive behaviors. We summarized aggressive behaviors using the Aggressive and Reactive Behavior Scale, which characterizes whether a resident has none, mild, moderate, or severe behavioral symptoms based on the presence and frequency of physical and verbal behaviors and resistance to care.^26,27 We included items that described pain, number of falls since admission or prior assessment, degree of urinary and bowel continence (always continent vs not always continent) and mobility device use to describe respondents’ health conditions and functional status. To characterize pain, we used veteran’s self-reported frequency and intensity of pain experienced in the prior 5 days and classified the experienced pain as none, mild, moderate, or severe. Finally, demographic characteristics included age and gender.

To determine functional status, we included measures of needing help to perform activities of daily living (ADLs). The MDS allows us to understand functional status ranging from ADLs lost early in the trajectory of functional decline (ie, bathing, hygiene) to those lost in the middle (ie, walking, dressing, toileting, transferring) to those lost late in the trajectory of functional decline (ie, bed mobility and eating).^28,29 To assess MFH veterans’ independence in mobility, we considered the veteran’s ability to walk without supervision or assistance in the hallway outside of their room, ability to move between their room and hallway, and ability to move throughout the house. Mobility includes use of an assistive device such as a cane, walker, or wheelchair if the veteran can use it without assistance. We summarized dependency in ADLs, using a combined score of dependence in bed mobility, transfer, locomotion on unit, dressing, eating, toilet use, and personal hygiene that ranges from 0 (independent) to 28 (completely dependent).³⁰ Additionally, we created 3-category variables to indicate the degree of dependence in performing ADLs (independent, supervision or assistance, and completely dependent).

Finally, we included diagnoses identified as active to explore differences in neurologic, mood, psychiatric, and chronic disease morbidity. In the MDS 3.0 assessment, an active diagnosis is defined as a diagnosis documented by a licensed independent practitioner in the prior 60 days that has affected the resident or their care in the prior 7 days.

Analysis

We conducted statistical analyses using Stata MP version 15.1 (StataCorp). We summarized demographic characteristics, cognitive function scores, depression scores, pain status, behavioral symptoms, incidence of falls, degree of continence, functional status, and comorbidities, using means and standard deviations for continuous variables and frequencies and proportions for categorical variables.

Results

Of the 92 MFH veterans in our sample, 85% were male and 83% were aged ≥ 65 years (Table 1). Veterans had an average length of stay of 927 days at the time of MDS assessment. More than half (55%) of MFH veterans had cognitive impairment (ranging from mild to severe). The mean (SD) depression score was 3.3 (3.9), indicating minimal depression. For veterans who could not complete the depression questionnaire, the mean (SD) staff-assessed depression score was 5.9 (5.5), suggesting mild depression. Overall, 22% of the sample had aggressive behaviors but only 7 were noted to be severe. Few residents had caregiver-reported wandering. Self-reported pain intensity indicated that 45% of the sample had mild, moderate, or severe pain. While more than half the cohort had complete bowel continence (53%), only 36% had complete urinary continence. Use of mobility devices was common, with 56% of residents using a wheelchair, 42% using a walker, and 14% using a cane. One-fourth of veterans had fallen at least once since admission to the MFH.

Of the 11 ADLs assessed, the percentage of MFH veterans requiring assistance with early and mid-loss ADLs ranged from 63% for transferring to 84% for bathing (Table 2). Even for the late-loss ADL of eating, 57% of the MFH cohort required assistance. Overall, MFH veterans had an average ADL dependency score of 11.

Discussion

In this study, we describe the characteristics of veterans receiving LTC in a sample of MFHs. This is the first study to assess veteran health and function across a group of MFHs. To help provide context for the description of MFH residents, we compared demographic characteristics, cognitive impairment, depression, pain, behaviors, functional status, and morbidity of veterans in the MFH program to long-stay residents in community nursing homes (eAppendix 1-3 available at doi:10.12788/fp.0102). A comparison with this reference population suggests that these MFH and nursing home cohorts are similar in terms of age, wandering behavior, incidence of falls, and prevalence of neurologic, psychiatric, and chronic diseases. Compared with nursing home residents, veterans in the MFH cohort had slightly higher mood symptom scores, were more likely to display aggressive behavior, and were more likely to report experiencing moderate and severe pain.

Additionally, MFH veterans displayed a lower level of cognitive impairment, fewer functional impairments, measured by the ADL dependency score, and were less likely to be bowel or bladder incontinent. Despite an overall lower ADL dependency score, a similar proportion of MFH veterans and nursing home residents were totally dependent in performing 7 of 11 ADLs and a higher proportion of MFH veterans were completely dependent for toileting (22% long-stay nursing home vs 31% MFH). The only ADLs for which there was a higher proportion of long-stay nursing home residents who were totally dependent compared with MFH residents were walking in room (54% long-stay nursing home vs 38% MFH), walking in the corridor (57% long-stay nursing home vs 33% MFH), and locomotion off the unit (36% long-stay nursing home vs 22% MFH).

While the rates of total ADL dependence among veterans in MFHs suggest that MFHs are providing care to a subset of veterans with high levels of functional impairment and care needs, MFHs are also providing care to veterans who are more independent in performing ADLs and who resemble low-care nursing home residents. A low-care nursing home resident is broadly defined as an one who does not need assistance performing late-loss ADLs (bed mobility, transferring, toileting, and eating) and who does not have the Resource Utilization Group classification of special rehab or clinically complex.^31,32 Due to their overall higher functional capacity, low-care residents, even those with chronic medical care needs, may be more appropriately cared for in less intensive care settings than in nursing homes. About 5% to 30% of long-stay nursing home residents can be classified as low care.^31,33-37 Additionally, a majority of newly admitted nursing home patients report a preference for or support community discharge rather than long-stay nursing home care, suggesting that many nursing home residents have the potential and desire to transition to a community-based setting.³³

Based on the prevalence of veterans in our sample who are similar to low-care nursing home residents and the national focus on shifting LTC to community-based settings, MFHs may be an ideal setting for both low-care nursing home residents and those seeking community-based alternatives to traditional, institutionalized LTC. Additionally, given that we observed greater behavioral and pain needs and similar rates of comorbidities in MFH veterans relative to long-stay nursing home residents, our results indicate that MFHs also have the capacity to care for veterans with higher care needs who desire community-based LTC.

Previous research identified barriers to program MFH growth that may contribute to referral of veterans with fewer ADL dependencies compared with long-stay nursing home residents. A key barrier to MFH referral is that nursing home referral requires selection of a home, whereas MFH referral involves matching veterans with appropriate caregivers, which requires time to align the veteran’s needs with the right caregiver in the right home.⁷ Given the rigors of finding a match, VA staff who refer veterans may preferentially refer veterans with greater ADL impairments to nursing homes, assuming that higher levels of care needs will complicate the matching process and reserve MFH referral for only the highest functioning candidates.¹⁹ However, the ADL data presented here indicate that many MFH residents with significant levels of ADL dependence are living in MFHs. Meeting the care needs of those who have higher ADL dependencies is possible because MFH coordinators and HBPC providers deliver individual, ongoing education to MFH caregivers about caring for MFH veterans and provide available resources needed to safely care for MFH veterans across the spectrum of ADL dependency.⁷

Veterans with higher levels of functional dependence may also be referred to nursing homes rather than to MFHs because of payment issues. Independent of the VA, veterans or their families negotiate a contract with their caregiver to pay out-of-pocket for MFH caregiving as well as room and board. Particularly for veterans who have military benefits to cover nursing home care costs, the out-of-pocket payment for veterans with high degrees of functional dependence increase as needs increase. These out-of-pocket payments may serve as a barrier to MFH enrollment. The proposed Long-Term Care Veterans Choice Act, which would allow the VA to pay for MFH care for eligible veterans may address this barrier.¹⁵

Another possible explanation for the higher rates of functional independence in the MFH cohort is that veterans with functional impairment are not being referred to MFHs. A previous study of the MFH program found that health care providers were often unaware of the program and as a result did not refer eligible veterans to this alternative LTC option.⁷ The changes proposed by the Long-Term Care Veterans Choice Act may result in an increase in demand in MFH care and thus increase awareness of the program among VA physicians.¹⁵

Limitations

There are several potential limitations in this study. First, there are limits to the generalizability of the MFH sample given that the sample of veterans was not randomly selected and that weights were not applied to account for nonresponse bias. Second, charting requirements in MFHs are less intensive compared with nursing home tracking. While the training for research nurses on how to conduct MDS assessments in MFHs was designed to simulate the process in nursing homes, MDS data were likely impacted by differences in charting practices. In addition, MFH caregivers may report certain items, such as aggressive behaviors, more often because they observe MFH veterans round-the-clock compared with NH caregivers who work in shifts and have a lower caregiver to resident ratio. The current data suggest differences in prevalence of behavioral symptoms.

Future studies should examine whether this reflects differences in the populations served or differences in how MFH caregivers track and manage behavioral symptoms. Third, this study was conducted at only MFH sites associated with 4 VAMCs, thus our findings may not be generalizable to veterans in other areas. Finally, there may be differences in the veterans who agreed to participate in the study compared with those who declined to participate. For example, it is possible that the eligible MFH veterans who declined to participate in this study were more functionally impaired than those who did participate. More than one-third (39%) of the family members of cognitively impaired MFH veterans who did not participate cited concerns about the veteran’s frailty as a primary reason for declining to participate. Consequently, the high level of functional status among veterans included in this study compared to nursing home residents may be in part a result of selection bias from more ADL-impaired veterans declining to participate in the study.

Conclusions

Although the MFH program has provided LTC nationally to veterans for nearly 2 decades, this study is the first to administer in-home MDS assessments to veterans in MFHs, allowing for a detailed description of cognitive, functional, and behavioral characteristics of MFH residents. In this study, we found that veterans currently receiving care in MFHs have a wide range of care needs. Our findings indicate that MFHs are caring for some veterans with high functional impairment as well as those who are completely independent in performing ADLs.

Moreover, these results are a preliminary attempt to assist VA health care providers in determining which veterans can be cared for in an MFH such that they can make informed referrals to this alternative LTC setting. To improve the generalizability of these findings, future studies should collect MDS 3.0 assessments longitudinally from a representative sample of veterans in MFHs. Further research is needed to explore how VA providers make the decision to refer a veteran to an MFH compared to a nursing home. Additionally, the percentage of veterans in this study who reported experiencing pain may indicate the need to identify innovative, integrated pain management programs for home settings.

Levels of insulinlike factor 3 (INSL3) drop noticeably in men who have abused anabolic androgenic steroids (AAS), even well after stoppage. The results suggest that the effects of AAS use on testosterone-producing Leydig cells may be long-lasting, as some clinicians have suspected. Although there is some variation of INSL3 levels among AAS users, the metric is more accurate than testosterone levels and could be a key element of future diagnostic tests.

Those are the conclusions of a new study, led by Jon Jarløv Rasmussen, MD, PhD, of the department of endocrinology at Rigshospitalet in Copenhagen*, published March 9, 2021, in the Journal of Clinical Endocrinology & Metabolism.  

Results mirror clinical experience  

The drop in levels, both among current and past users, is in keeping with clinical experience of endocrinologists, according to Channa Jayasena, MD, PhD, a reproductive endocrinologist at Imperial College London. He suspects lasting damage in former and current users who come to him when they discover their sperm count is low. "How long that damage lasts is another matter," Dr. Jayasena, who was not involved in the study, said in an interview.   

In search of a reliable measure  

Low testosterone levels have been shown to be associated with AAS use in some studies, but not in others. That inconsistency led the researchers in search of a more reliable measure. "Serum testosterone is not a stable marker but can fluctuate considerably within minutes to hours, whereas serum insulinlike factor 3 [levels] do not," said Dr. Rasmussen.  
INSL3 appears to be involved in bone metabolism regulation as well as spermatogenesis.  

Dr. Rasmussen agreed that INSL3 levels could be clinically useful for tracking Leydig cell function, especially in combination with other hormone markers like serum testosterone and gonadotropins. The group is now considering a clinical trial for treatment of hypogonadal men following illicit use of anabolic steroids, which will include INSL3 serum levels as a planned endpoint.  

The researchers conducted a cross-sectional study of men aged 18-50 years who had participated in recreational strength training. Cohort 1 included 37 AAS users, 33 former users, and 30 never users. Cohort 2 included 9 current users, 9 former users, and 14 never users. They assigned participant AAS use status based on self-reporting, along with measurement of biomedical parameters including gonadotropins, sexual hormone-binding globulin (SHBG), and hematocrit.  
Compared with never users' median value of 0.59 mcg/L, INSL3 serum levels were lower among current AAS (median, 0.04 mcg/L; P < .001) and former AAS (0.39 mcg/L; P = .005) users. A linear multivariate regression that adjusted for luteinizing hormone, SHBG, age, body-fat percentage, smoking status, use of other illicit drugs found lower levels among former users, compared with never users (mean difference, -0.16 mcg/L; P = .011). 

An analysis of elapsed duration since AAS cessation found longer duration of AAS use was associated with reduced INSL3 levels (mean difference, -0.08; P = .022). 

Although serum inhibin B levels reached the levels of never users after about 21 months, and luteinizing hormone levels recovered in about 12 months, neither serum testosterone nor INSL3 levels recovered in former users. 

The study authors received funding from Anti Doping Denmark. Dr. Jayasena has no relevant financial disclosures. 

*Dr. Rasmussen's affiliation has been corrected.

Levels of insulinlike factor 3 (INSL3) drop noticeably in men who have abused anabolic androgenic steroids (AAS), even well after stoppage. The results suggest that the effects of AAS use on testosterone-producing Leydig cells may be long-lasting, as some clinicians have suspected. Although there is some variation of INSL3 levels among AAS users, the metric is more accurate than testosterone levels and could be a key element of future diagnostic tests.

Those are the conclusions of a new study, led by Jon Jarløv Rasmussen, MD, PhD, of the department of endocrinology at Rigshospitalet in Copenhagen*, published March 9, 2021, in the Journal of Clinical Endocrinology & Metabolism.  

Results mirror clinical experience  

The drop in levels, both among current and past users, is in keeping with clinical experience of endocrinologists, according to Channa Jayasena, MD, PhD, a reproductive endocrinologist at Imperial College London. He suspects lasting damage in former and current users who come to him when they discover their sperm count is low. "How long that damage lasts is another matter," Dr. Jayasena, who was not involved in the study, said in an interview.   

In search of a reliable measure  

Low testosterone levels have been shown to be associated with AAS use in some studies, but not in others. That inconsistency led the researchers in search of a more reliable measure. "Serum testosterone is not a stable marker but can fluctuate considerably within minutes to hours, whereas serum insulinlike factor 3 [levels] do not," said Dr. Rasmussen.  
INSL3 appears to be involved in bone metabolism regulation as well as spermatogenesis.  

Dr. Rasmussen agreed that INSL3 levels could be clinically useful for tracking Leydig cell function, especially in combination with other hormone markers like serum testosterone and gonadotropins. The group is now considering a clinical trial for treatment of hypogonadal men following illicit use of anabolic steroids, which will include INSL3 serum levels as a planned endpoint.  

The researchers conducted a cross-sectional study of men aged 18-50 years who had participated in recreational strength training. Cohort 1 included 37 AAS users, 33 former users, and 30 never users. Cohort 2 included 9 current users, 9 former users, and 14 never users. They assigned participant AAS use status based on self-reporting, along with measurement of biomedical parameters including gonadotropins, sexual hormone-binding globulin (SHBG), and hematocrit.  
Compared with never users' median value of 0.59 mcg/L, INSL3 serum levels were lower among current AAS (median, 0.04 mcg/L; P < .001) and former AAS (0.39 mcg/L; P = .005) users. A linear multivariate regression that adjusted for luteinizing hormone, SHBG, age, body-fat percentage, smoking status, use of other illicit drugs found lower levels among former users, compared with never users (mean difference, -0.16 mcg/L; P = .011). 

An analysis of elapsed duration since AAS cessation found longer duration of AAS use was associated with reduced INSL3 levels (mean difference, -0.08; P = .022). 

Although serum inhibin B levels reached the levels of never users after about 21 months, and luteinizing hormone levels recovered in about 12 months, neither serum testosterone nor INSL3 levels recovered in former users. 

The study authors received funding from Anti Doping Denmark. Dr. Jayasena has no relevant financial disclosures. 

*Dr. Rasmussen's affiliation has been corrected.

Levels of insulinlike factor 3 (INSL3) drop noticeably in men who have abused anabolic androgenic steroids (AAS), even well after stoppage. The results suggest that the effects of AAS use on testosterone-producing Leydig cells may be long-lasting, as some clinicians have suspected. Although there is some variation of INSL3 levels among AAS users, the metric is more accurate than testosterone levels and could be a key element of future diagnostic tests.

Those are the conclusions of a new study, led by Jon Jarløv Rasmussen, MD, PhD, of the department of endocrinology at Rigshospitalet in Copenhagen*, published March 9, 2021, in the Journal of Clinical Endocrinology & Metabolism.  

Results mirror clinical experience  

The drop in levels, both among current and past users, is in keeping with clinical experience of endocrinologists, according to Channa Jayasena, MD, PhD, a reproductive endocrinologist at Imperial College London. He suspects lasting damage in former and current users who come to him when they discover their sperm count is low. "How long that damage lasts is another matter," Dr. Jayasena, who was not involved in the study, said in an interview.   

In search of a reliable measure  

Low testosterone levels have been shown to be associated with AAS use in some studies, but not in others. That inconsistency led the researchers in search of a more reliable measure. "Serum testosterone is not a stable marker but can fluctuate considerably within minutes to hours, whereas serum insulinlike factor 3 [levels] do not," said Dr. Rasmussen.  
INSL3 appears to be involved in bone metabolism regulation as well as spermatogenesis.  

Dr. Rasmussen agreed that INSL3 levels could be clinically useful for tracking Leydig cell function, especially in combination with other hormone markers like serum testosterone and gonadotropins. The group is now considering a clinical trial for treatment of hypogonadal men following illicit use of anabolic steroids, which will include INSL3 serum levels as a planned endpoint.  

The researchers conducted a cross-sectional study of men aged 18-50 years who had participated in recreational strength training. Cohort 1 included 37 AAS users, 33 former users, and 30 never users. Cohort 2 included 9 current users, 9 former users, and 14 never users. They assigned participant AAS use status based on self-reporting, along with measurement of biomedical parameters including gonadotropins, sexual hormone-binding globulin (SHBG), and hematocrit.  
Compared with never users' median value of 0.59 mcg/L, INSL3 serum levels were lower among current AAS (median, 0.04 mcg/L; P < .001) and former AAS (0.39 mcg/L; P = .005) users. A linear multivariate regression that adjusted for luteinizing hormone, SHBG, age, body-fat percentage, smoking status, use of other illicit drugs found lower levels among former users, compared with never users (mean difference, -0.16 mcg/L; P = .011). 

An analysis of elapsed duration since AAS cessation found longer duration of AAS use was associated with reduced INSL3 levels (mean difference, -0.08; P = .022). 

Although serum inhibin B levels reached the levels of never users after about 21 months, and luteinizing hormone levels recovered in about 12 months, neither serum testosterone nor INSL3 levels recovered in former users. 

The study authors received funding from Anti Doping Denmark. Dr. Jayasena has no relevant financial disclosures. 

*Dr. Rasmussen's affiliation has been corrected.

Diagnosis of bleeding disorders in girls and women can lag behind diagnosis in boys and men by more than a decade, meaning needless delays in treatment and poor quality of life for many with hemophilia or related conditions.

“There is increasing awareness about issues faced by women and girls with inherited bleeding disorders, but disparities still exist both in both access to diagnosis and treatment,” said Roseline D’Oiron, MD, from Hôpital Bicêtre in Paris.

“Diagnosis, when it is made, is often made late, particularly in women. Indeed, a recent study from the European Hemophilia Consortium including more than 700 women with bleeding disorders showed that the median age at diagnosis was 16 years old,” she said during the annual congress of the European Association for Haemophilia and Allied Disorders.

She said that delayed diagnosis of bleeding disorders in women and girls may be caused by a lack of knowledge by patients, families, and general practitioners about family history of bleeding disorders, abnormal bleeding events, and heavy menstrual bleeding. In addition, despite the frequency and severity of heavy bleeding events, patients, their families, and caregivers may underestimate the effect on the patient’s quality of life.
 

Disparities documented

Dr. D’Oiron pointed to several studies showing clear sex-based disparities in time to diagnosis. For example, a study published in Haemophilia showed that in 22 girls with hemophilia A or hemophilia B, the diagnosis of severe hemophilia was delayed by a median of 6.5 months compared with the diagnosis in boys, and a diagnosis of moderate hemophilia in girls was delayed by a median of 39 months.

In a second, single-center study comparing 44 women and girls with mild hemophilia (factor VIII or factor XI levels from 5 to 50 IU/dL) with 77 men and boys with mild hemophilia, the mean age at diagnosis was 31.63 years versus 19.18 years, respectively – a delay of 12.45 years.

A third study comparing 442 girls/women and 442 boys/men with mild hemophilia in France showed a difference of 6.07 years in diagnosis: the median age for girls/women at diagnosis was 16.91 years versus10.84 years for boys/men.
 

Why it matters

Dr. D’Oiron described the case of a patient named Clare, who first experienced, at age 8, 12 hours of bleeding following a dental procedure. At age 12.5, she began having heavy menstrual bleeding, causing her to miss school for a few days each month, to be feel tired, and have poor-quality sleep.

Despite repeated bleeding episodes, severe anemia, and iron deficiency, her hemophilia was not suspected until after her 16th birthday, and a definitive diagnosis of hemophilia in both Clare and her mother was finally made when Clare was past 17, when a nonsense variant factor in F8, the gene encoding for factor VIII, was detected.

“For Clare, it took more the 8 years after the first bleeding symptoms, and nearly 4 years after presenting with heavy menstrual bleeding to recognize that she had a bleeding problem,” she said.

In total, Clare had about 450 days of heavy menstrual bleeding, causing her to miss an estimated 140 days of school because of the delayed diagnosis and treatment.

“In my view, this is the main argument why it is urgent for these patients to achieve diagnosis early: this is to reduce the duration [of] a very poor quality of life,” Dr. D’Oiron said.
 

Barriers to diagnosis

Patients and families have reported difficulty distinguishing normal bleeding from abnormal symptoms, and girls may be reluctant to discuss their symptoms with their family or peers. In addition, primary care practitioners may not recognize the severity of the symptoms and therefore may not refer patients to hematologists for further workup.

These findings emphasize the need for improved tools to help patients differentiate between normal and abnormal bleeding, using symptom recognition–based language tools that can lead to early testing and application of accurate diagnostic tools, she said.

Standardization of definitions can help to improve screening and diagnosis, Dr. D’Oiron said, pointing to a recent study in Blood Advances proposing definitions for future research in von Willebrand disease.

For example, the authors of that study proposed a definition of heavy menstrual bleeding to include any of the following:

• Bleeding lasting 8 or more days
• Bleeding that consistently soaks through one or more sanitary protections every 2 hours on multiple days
• Requires use of more than one sanitary protection item at a time
• Requires changing sanitary protection during the night
• Is associated with repeat passing of blood clots
• Has a Pictorial Blood Assessment Chart score greater than 100.
•  

Problem and solutions

Answering the question posed in the title of her talk, Dr. D’Oiron said: “Yes, we do have a problem with the diagnosis of bleeding disorders in women and girls, but we also have solutions.”

The solutions include family and patient outreach efforts; communication to improve awareness; inclusion of general practitioners in the circle of care; and early screening, diagnosis, and treatment.

A bleeding disorders specialist who was not involved in the study said that Dr. D’Oiron’s report closely reflects what she sees in the clinic.

“I do pediatrics, and usually what happens is that I see a teenager with heavy menstrual bleeding and we take her history, and we find out that Mom and multiple female family members have had horrible menstrual bleeding, possibly many of whom have had hysterectomies for it, and then diagnosing the parents and other family members after diagnosing the girl that we’re seeing” said Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee.

“It is unfortunately a very real thing,” she added.

Reasons for the delay likely include lack of awareness of bleeding disorders.

“If you present to a hematologist, we think about bleeding disorders, but if you present to a primary care physician, they don’t always have that on their radar,” she said.

Additionally, a girl from a family with a history of heavy menstrual bleeding may just assume that what she is experiencing is “normal,” despite the serious affect it has on her quality of life, Dr. Flood said.

Dr. D’Oiron’s research is supported by her institution, the French Hemophilia Association, FranceCoag and Mhemon, the European Hemophilia Consortium, and the World Federation of Hemophilia. She reported advisory board or invited speaker activities for multiple companies. Dr. Flood reported having no conflicts of interest to disclose.

Diagnosis of bleeding disorders in girls and women can lag behind diagnosis in boys and men by more than a decade, meaning needless delays in treatment and poor quality of life for many with hemophilia or related conditions.

“There is increasing awareness about issues faced by women and girls with inherited bleeding disorders, but disparities still exist both in both access to diagnosis and treatment,” said Roseline D’Oiron, MD, from Hôpital Bicêtre in Paris.

“Diagnosis, when it is made, is often made late, particularly in women. Indeed, a recent study from the European Hemophilia Consortium including more than 700 women with bleeding disorders showed that the median age at diagnosis was 16 years old,” she said during the annual congress of the European Association for Haemophilia and Allied Disorders.

She said that delayed diagnosis of bleeding disorders in women and girls may be caused by a lack of knowledge by patients, families, and general practitioners about family history of bleeding disorders, abnormal bleeding events, and heavy menstrual bleeding. In addition, despite the frequency and severity of heavy bleeding events, patients, their families, and caregivers may underestimate the effect on the patient’s quality of life.
 

Disparities documented

Dr. D’Oiron pointed to several studies showing clear sex-based disparities in time to diagnosis. For example, a study published in Haemophilia showed that in 22 girls with hemophilia A or hemophilia B, the diagnosis of severe hemophilia was delayed by a median of 6.5 months compared with the diagnosis in boys, and a diagnosis of moderate hemophilia in girls was delayed by a median of 39 months.

In a second, single-center study comparing 44 women and girls with mild hemophilia (factor VIII or factor XI levels from 5 to 50 IU/dL) with 77 men and boys with mild hemophilia, the mean age at diagnosis was 31.63 years versus 19.18 years, respectively – a delay of 12.45 years.

A third study comparing 442 girls/women and 442 boys/men with mild hemophilia in France showed a difference of 6.07 years in diagnosis: the median age for girls/women at diagnosis was 16.91 years versus10.84 years for boys/men.
 

Why it matters

Dr. D’Oiron described the case of a patient named Clare, who first experienced, at age 8, 12 hours of bleeding following a dental procedure. At age 12.5, she began having heavy menstrual bleeding, causing her to miss school for a few days each month, to be feel tired, and have poor-quality sleep.

Despite repeated bleeding episodes, severe anemia, and iron deficiency, her hemophilia was not suspected until after her 16th birthday, and a definitive diagnosis of hemophilia in both Clare and her mother was finally made when Clare was past 17, when a nonsense variant factor in F8, the gene encoding for factor VIII, was detected.

“For Clare, it took more the 8 years after the first bleeding symptoms, and nearly 4 years after presenting with heavy menstrual bleeding to recognize that she had a bleeding problem,” she said.

In total, Clare had about 450 days of heavy menstrual bleeding, causing her to miss an estimated 140 days of school because of the delayed diagnosis and treatment.

“In my view, this is the main argument why it is urgent for these patients to achieve diagnosis early: this is to reduce the duration [of] a very poor quality of life,” Dr. D’Oiron said.
 

Barriers to diagnosis

Patients and families have reported difficulty distinguishing normal bleeding from abnormal symptoms, and girls may be reluctant to discuss their symptoms with their family or peers. In addition, primary care practitioners may not recognize the severity of the symptoms and therefore may not refer patients to hematologists for further workup.

These findings emphasize the need for improved tools to help patients differentiate between normal and abnormal bleeding, using symptom recognition–based language tools that can lead to early testing and application of accurate diagnostic tools, she said.

Standardization of definitions can help to improve screening and diagnosis, Dr. D’Oiron said, pointing to a recent study in Blood Advances proposing definitions for future research in von Willebrand disease.

For example, the authors of that study proposed a definition of heavy menstrual bleeding to include any of the following:

• Bleeding lasting 8 or more days
• Bleeding that consistently soaks through one or more sanitary protections every 2 hours on multiple days
• Requires use of more than one sanitary protection item at a time
• Requires changing sanitary protection during the night
• Is associated with repeat passing of blood clots
• Has a Pictorial Blood Assessment Chart score greater than 100.
•  

Problem and solutions

Answering the question posed in the title of her talk, Dr. D’Oiron said: “Yes, we do have a problem with the diagnosis of bleeding disorders in women and girls, but we also have solutions.”

The solutions include family and patient outreach efforts; communication to improve awareness; inclusion of general practitioners in the circle of care; and early screening, diagnosis, and treatment.

A bleeding disorders specialist who was not involved in the study said that Dr. D’Oiron’s report closely reflects what she sees in the clinic.

“I do pediatrics, and usually what happens is that I see a teenager with heavy menstrual bleeding and we take her history, and we find out that Mom and multiple female family members have had horrible menstrual bleeding, possibly many of whom have had hysterectomies for it, and then diagnosing the parents and other family members after diagnosing the girl that we’re seeing” said Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee.

“It is unfortunately a very real thing,” she added.

Reasons for the delay likely include lack of awareness of bleeding disorders.

“If you present to a hematologist, we think about bleeding disorders, but if you present to a primary care physician, they don’t always have that on their radar,” she said.

Additionally, a girl from a family with a history of heavy menstrual bleeding may just assume that what she is experiencing is “normal,” despite the serious affect it has on her quality of life, Dr. Flood said.

Dr. D’Oiron’s research is supported by her institution, the French Hemophilia Association, FranceCoag and Mhemon, the European Hemophilia Consortium, and the World Federation of Hemophilia. She reported advisory board or invited speaker activities for multiple companies. Dr. Flood reported having no conflicts of interest to disclose.

Diagnosis of bleeding disorders in girls and women can lag behind diagnosis in boys and men by more than a decade, meaning needless delays in treatment and poor quality of life for many with hemophilia or related conditions.

“There is increasing awareness about issues faced by women and girls with inherited bleeding disorders, but disparities still exist both in both access to diagnosis and treatment,” said Roseline D’Oiron, MD, from Hôpital Bicêtre in Paris.

“Diagnosis, when it is made, is often made late, particularly in women. Indeed, a recent study from the European Hemophilia Consortium including more than 700 women with bleeding disorders showed that the median age at diagnosis was 16 years old,” she said during the annual congress of the European Association for Haemophilia and Allied Disorders.

She said that delayed diagnosis of bleeding disorders in women and girls may be caused by a lack of knowledge by patients, families, and general practitioners about family history of bleeding disorders, abnormal bleeding events, and heavy menstrual bleeding. In addition, despite the frequency and severity of heavy bleeding events, patients, their families, and caregivers may underestimate the effect on the patient’s quality of life.
 

Disparities documented

Dr. D’Oiron pointed to several studies showing clear sex-based disparities in time to diagnosis. For example, a study published in Haemophilia showed that in 22 girls with hemophilia A or hemophilia B, the diagnosis of severe hemophilia was delayed by a median of 6.5 months compared with the diagnosis in boys, and a diagnosis of moderate hemophilia in girls was delayed by a median of 39 months.

In a second, single-center study comparing 44 women and girls with mild hemophilia (factor VIII or factor XI levels from 5 to 50 IU/dL) with 77 men and boys with mild hemophilia, the mean age at diagnosis was 31.63 years versus 19.18 years, respectively – a delay of 12.45 years.

A third study comparing 442 girls/women and 442 boys/men with mild hemophilia in France showed a difference of 6.07 years in diagnosis: the median age for girls/women at diagnosis was 16.91 years versus10.84 years for boys/men.
 

Why it matters

Dr. D’Oiron described the case of a patient named Clare, who first experienced, at age 8, 12 hours of bleeding following a dental procedure. At age 12.5, she began having heavy menstrual bleeding, causing her to miss school for a few days each month, to be feel tired, and have poor-quality sleep.

Despite repeated bleeding episodes, severe anemia, and iron deficiency, her hemophilia was not suspected until after her 16th birthday, and a definitive diagnosis of hemophilia in both Clare and her mother was finally made when Clare was past 17, when a nonsense variant factor in F8, the gene encoding for factor VIII, was detected.

“For Clare, it took more the 8 years after the first bleeding symptoms, and nearly 4 years after presenting with heavy menstrual bleeding to recognize that she had a bleeding problem,” she said.

In total, Clare had about 450 days of heavy menstrual bleeding, causing her to miss an estimated 140 days of school because of the delayed diagnosis and treatment.

“In my view, this is the main argument why it is urgent for these patients to achieve diagnosis early: this is to reduce the duration [of] a very poor quality of life,” Dr. D’Oiron said.
 

Barriers to diagnosis

Patients and families have reported difficulty distinguishing normal bleeding from abnormal symptoms, and girls may be reluctant to discuss their symptoms with their family or peers. In addition, primary care practitioners may not recognize the severity of the symptoms and therefore may not refer patients to hematologists for further workup.

These findings emphasize the need for improved tools to help patients differentiate between normal and abnormal bleeding, using symptom recognition–based language tools that can lead to early testing and application of accurate diagnostic tools, she said.

Standardization of definitions can help to improve screening and diagnosis, Dr. D’Oiron said, pointing to a recent study in Blood Advances proposing definitions for future research in von Willebrand disease.

For example, the authors of that study proposed a definition of heavy menstrual bleeding to include any of the following:

• Bleeding lasting 8 or more days
• Bleeding that consistently soaks through one or more sanitary protections every 2 hours on multiple days
• Requires use of more than one sanitary protection item at a time
• Requires changing sanitary protection during the night
• Is associated with repeat passing of blood clots
• Has a Pictorial Blood Assessment Chart score greater than 100.
•  

Problem and solutions

Answering the question posed in the title of her talk, Dr. D’Oiron said: “Yes, we do have a problem with the diagnosis of bleeding disorders in women and girls, but we also have solutions.”

The solutions include family and patient outreach efforts; communication to improve awareness; inclusion of general practitioners in the circle of care; and early screening, diagnosis, and treatment.

A bleeding disorders specialist who was not involved in the study said that Dr. D’Oiron’s report closely reflects what she sees in the clinic.

“I do pediatrics, and usually what happens is that I see a teenager with heavy menstrual bleeding and we take her history, and we find out that Mom and multiple female family members have had horrible menstrual bleeding, possibly many of whom have had hysterectomies for it, and then diagnosing the parents and other family members after diagnosing the girl that we’re seeing” said Veronica H. Flood, MD, from the Medical College of Wisconsin, Milwaukee.

“It is unfortunately a very real thing,” she added.

Reasons for the delay likely include lack of awareness of bleeding disorders.

“If you present to a hematologist, we think about bleeding disorders, but if you present to a primary care physician, they don’t always have that on their radar,” she said.

Additionally, a girl from a family with a history of heavy menstrual bleeding may just assume that what she is experiencing is “normal,” despite the serious affect it has on her quality of life, Dr. Flood said.

Dr. D’Oiron’s research is supported by her institution, the French Hemophilia Association, FranceCoag and Mhemon, the European Hemophilia Consortium, and the World Federation of Hemophilia. She reported advisory board or invited speaker activities for multiple companies. Dr. Flood reported having no conflicts of interest to disclose.

Scenario

A GI faculty member is approached by two medical students who are planning careers in gastroenterology. They are interested in research projects and are very willing to dedicate the necessary time and energy. The faculty member is impressed by their desire and finds themselves recalling their own unsuccessful medical school search for a research mentor. Inspired by their enthusiasm and a desire to “give back,” the faculty member agrees to mentor them and helps them find suitable projects. Primarily because of the students’ hard work and fueled by their desire to produce results that will help their residency applications, the work progresses rapidly. Both students have separate abstracts accepted at a national meeting.

When COVID-19 hits, the faculty member is asked by their department to take on additional administrative and clinical work. They feel they cannot say no. Soon the faculty member finds it difficult to manage these new responsibilities on top of their many research projects, numerous clinical obligations, and additional pressures outside of work. They find they have no time for mentoring or even adequate sleep. Facing burnout, the faculty member is uncertain what to do for these hard-working and very gifted students. How would you recommend they manage their mentoring obligations?
 

Discussion

Mentorship is a cornerstone of academic medicine. In fact, it has been shown that academic clinicians who serve as mentors publish more papers, get more grants, are promoted faster, and are more likely to stay at their academic institutions with greater career satisfaction.¹ However, not every mentor-mentee relationship is mutually beneficial. Usually, it’s the mentees that disproportionately suffer the consequences of a suboptimal relationship.²

Mentorship malpractice occurs when mentors’ behavior crosses a threshold that places the mentees’ success at risk.^1,2 While the case above highlights a specific scenario where multiple issues are unfolding, the ability to recognize, address, and most importantly prevent mentorship malpractice ultimately benefits both mentees and mentors.

Understanding the various types of mentorship malpractice is helpful for prevention and course correction. As described by Chopra and colleagues, there are multiple types of passive and active mentorship malpractice.² The passive forms are characterized by a lack of face-to-face meeting time with mentees and/or a lack of advocacy on the mentees’ behalf. Meanwhile, the active forms occur when the mentor exhibits self-serving behaviors. These can include listing themselves as first author on a mentee’s project or discouraging a mentee from working with other mentors. Mentors must be able to self-check, seek feedback from mentees, and encourage mentees to further their professional networks beyond the boundaries of what the mentor alone can offer. Doing so helps create new opportunities and helps ensure a mutually beneficial relationship.

A great initial step to prevent passive and active mentorship malpractice is to leverage the benefits of team mentorship.^2,3 At its core, team mentorship capitalizes on the collective contributions of multiple mentors. Doing so not only provides security during uncertain times, but also allows for a diversity of perspectives, distribution of workload among mentors, and additional support for mentees.^3,4 Team mentorship it is particularly important during this current global health crisis, and such an approach from the outset could have significantly improved the scenario above.

For the above scenario, likely a transition in mentorship would be needed. Such transitions, whether short term or long term, require transparency, honesty, and willingness to engage in difficult conversations with mentees. Whether the mentor in the above case engages another faculty to take on the mentees or chooses to find a colleague who will agree to take on other competing demands, it will require time, effort, and energy – all of which are in short supply. When team mentorship is established from the outset, such transitions of mentorship can occur seamlessly and with more ease for all.

Additional considerations for successful mentoring of medical students or early-career physicians include understanding generational differences between the mentor and their mentees. As outlined by Waljee and colleagues, the next generation of trainees and physicians may act in ways that deviate from the norms of academic medicine’s tradition. As a mentor, it is imperative to understand these actions are not intended to disrupt the traditions and norms of health systems.⁵ For example, the use of technology during rounds can often be misconstrued as disrespectful. However, the underlying intent in many cases is to answer a question or access a helpful reference.

Seeing behavior and actions from the perspective of the mentee is one of the many ways to support and sustain successful mentoring relationships. A mindful approach benefits both mentees and mentors; this includes reflecting on the underlying motives for mentorship and cultivating gratitude for the relationships formed.⁶ While these steps may seem trivial, gratitude promotes happiness, trust, motivation, and respect. It can be felt by others, including mentees.

As mentors continue to shape the future, they have an ethical obligation to care for themselves, in addition to their mentees. In addition to avoiding mentorship malpractice, engaging in team mentorship, and incorporating mindful mentoring, an emphasis on self-care is critical.⁷ Taking time to recharge is essential. It allows one to be fully present, while also setting an example for the mentee. Explicitly addressing self-care for both mentor and mentee is a part of mindful mentorship, with benefits for all.⁶
 

Three key points:

1. Awareness of mentorship malpractice

2. Importance of team mentorship

3. Benefits of mindful mentorship

Mr. Rodoni is with the University of Michigan Medical School and Stephen M. Ross School of Business, Ann Arbor, Mich. Dr. Fessel is a professor of radiology in the department of radiology at Michigan Medicine, Ann Arbor. They reported having no disclosures relevant to this article.

References:

1. Chopra V et al. JAMA Intern Med. 2018 Feb;178:175-6.

2. Chopra V et al. JAMA. 2016 Apr 12;315:1453-4.

3. Chopra V et al. The Mentoring Guide: Helping Mentors & Mentees Succeed. Ann Arbor: Michigan Publishing, 2019.

4. Rodoni BM et al. Annals of Surgery. 2020 Aug;272(2):e151-2.

5. Waljee JF et al. JAMA. 2018 Apr 17;319(15):1547-8.

6. Chopra V and Saint S. Healthc (Amst). 2020 Mar;8(1):100390.

7. Fessell D et al. “Mentoring During a Crisis.” Harvard Business Review. 2020 Oct 29.

Scenario

A GI faculty member is approached by two medical students who are planning careers in gastroenterology. They are interested in research projects and are very willing to dedicate the necessary time and energy. The faculty member is impressed by their desire and finds themselves recalling their own unsuccessful medical school search for a research mentor. Inspired by their enthusiasm and a desire to “give back,” the faculty member agrees to mentor them and helps them find suitable projects. Primarily because of the students’ hard work and fueled by their desire to produce results that will help their residency applications, the work progresses rapidly. Both students have separate abstracts accepted at a national meeting.

When COVID-19 hits, the faculty member is asked by their department to take on additional administrative and clinical work. They feel they cannot say no. Soon the faculty member finds it difficult to manage these new responsibilities on top of their many research projects, numerous clinical obligations, and additional pressures outside of work. They find they have no time for mentoring or even adequate sleep. Facing burnout, the faculty member is uncertain what to do for these hard-working and very gifted students. How would you recommend they manage their mentoring obligations?
 

Discussion

Mentorship is a cornerstone of academic medicine. In fact, it has been shown that academic clinicians who serve as mentors publish more papers, get more grants, are promoted faster, and are more likely to stay at their academic institutions with greater career satisfaction.¹ However, not every mentor-mentee relationship is mutually beneficial. Usually, it’s the mentees that disproportionately suffer the consequences of a suboptimal relationship.²

Mentorship malpractice occurs when mentors’ behavior crosses a threshold that places the mentees’ success at risk.^1,2 While the case above highlights a specific scenario where multiple issues are unfolding, the ability to recognize, address, and most importantly prevent mentorship malpractice ultimately benefits both mentees and mentors.

Understanding the various types of mentorship malpractice is helpful for prevention and course correction. As described by Chopra and colleagues, there are multiple types of passive and active mentorship malpractice.² The passive forms are characterized by a lack of face-to-face meeting time with mentees and/or a lack of advocacy on the mentees’ behalf. Meanwhile, the active forms occur when the mentor exhibits self-serving behaviors. These can include listing themselves as first author on a mentee’s project or discouraging a mentee from working with other mentors. Mentors must be able to self-check, seek feedback from mentees, and encourage mentees to further their professional networks beyond the boundaries of what the mentor alone can offer. Doing so helps create new opportunities and helps ensure a mutually beneficial relationship.

A great initial step to prevent passive and active mentorship malpractice is to leverage the benefits of team mentorship.^2,3 At its core, team mentorship capitalizes on the collective contributions of multiple mentors. Doing so not only provides security during uncertain times, but also allows for a diversity of perspectives, distribution of workload among mentors, and additional support for mentees.^3,4 Team mentorship it is particularly important during this current global health crisis, and such an approach from the outset could have significantly improved the scenario above.

For the above scenario, likely a transition in mentorship would be needed. Such transitions, whether short term or long term, require transparency, honesty, and willingness to engage in difficult conversations with mentees. Whether the mentor in the above case engages another faculty to take on the mentees or chooses to find a colleague who will agree to take on other competing demands, it will require time, effort, and energy – all of which are in short supply. When team mentorship is established from the outset, such transitions of mentorship can occur seamlessly and with more ease for all.

Additional considerations for successful mentoring of medical students or early-career physicians include understanding generational differences between the mentor and their mentees. As outlined by Waljee and colleagues, the next generation of trainees and physicians may act in ways that deviate from the norms of academic medicine’s tradition. As a mentor, it is imperative to understand these actions are not intended to disrupt the traditions and norms of health systems.⁵ For example, the use of technology during rounds can often be misconstrued as disrespectful. However, the underlying intent in many cases is to answer a question or access a helpful reference.

Seeing behavior and actions from the perspective of the mentee is one of the many ways to support and sustain successful mentoring relationships. A mindful approach benefits both mentees and mentors; this includes reflecting on the underlying motives for mentorship and cultivating gratitude for the relationships formed.⁶ While these steps may seem trivial, gratitude promotes happiness, trust, motivation, and respect. It can be felt by others, including mentees.

As mentors continue to shape the future, they have an ethical obligation to care for themselves, in addition to their mentees. In addition to avoiding mentorship malpractice, engaging in team mentorship, and incorporating mindful mentoring, an emphasis on self-care is critical.⁷ Taking time to recharge is essential. It allows one to be fully present, while also setting an example for the mentee. Explicitly addressing self-care for both mentor and mentee is a part of mindful mentorship, with benefits for all.⁶
 

Three key points:

1. Awareness of mentorship malpractice

2. Importance of team mentorship

3. Benefits of mindful mentorship

Mr. Rodoni is with the University of Michigan Medical School and Stephen M. Ross School of Business, Ann Arbor, Mich. Dr. Fessel is a professor of radiology in the department of radiology at Michigan Medicine, Ann Arbor. They reported having no disclosures relevant to this article.

References:

1. Chopra V et al. JAMA Intern Med. 2018 Feb;178:175-6.

2. Chopra V et al. JAMA. 2016 Apr 12;315:1453-4.

3. Chopra V et al. The Mentoring Guide: Helping Mentors & Mentees Succeed. Ann Arbor: Michigan Publishing, 2019.

4. Rodoni BM et al. Annals of Surgery. 2020 Aug;272(2):e151-2.

5. Waljee JF et al. JAMA. 2018 Apr 17;319(15):1547-8.

6. Chopra V and Saint S. Healthc (Amst). 2020 Mar;8(1):100390.

7. Fessell D et al. “Mentoring During a Crisis.” Harvard Business Review. 2020 Oct 29.

Scenario

A GI faculty member is approached by two medical students who are planning careers in gastroenterology. They are interested in research projects and are very willing to dedicate the necessary time and energy. The faculty member is impressed by their desire and finds themselves recalling their own unsuccessful medical school search for a research mentor. Inspired by their enthusiasm and a desire to “give back,” the faculty member agrees to mentor them and helps them find suitable projects. Primarily because of the students’ hard work and fueled by their desire to produce results that will help their residency applications, the work progresses rapidly. Both students have separate abstracts accepted at a national meeting.

When COVID-19 hits, the faculty member is asked by their department to take on additional administrative and clinical work. They feel they cannot say no. Soon the faculty member finds it difficult to manage these new responsibilities on top of their many research projects, numerous clinical obligations, and additional pressures outside of work. They find they have no time for mentoring or even adequate sleep. Facing burnout, the faculty member is uncertain what to do for these hard-working and very gifted students. How would you recommend they manage their mentoring obligations?
 

Discussion

Mentorship is a cornerstone of academic medicine. In fact, it has been shown that academic clinicians who serve as mentors publish more papers, get more grants, are promoted faster, and are more likely to stay at their academic institutions with greater career satisfaction.¹ However, not every mentor-mentee relationship is mutually beneficial. Usually, it’s the mentees that disproportionately suffer the consequences of a suboptimal relationship.²

Mentorship malpractice occurs when mentors’ behavior crosses a threshold that places the mentees’ success at risk.^1,2 While the case above highlights a specific scenario where multiple issues are unfolding, the ability to recognize, address, and most importantly prevent mentorship malpractice ultimately benefits both mentees and mentors.

Understanding the various types of mentorship malpractice is helpful for prevention and course correction. As described by Chopra and colleagues, there are multiple types of passive and active mentorship malpractice.² The passive forms are characterized by a lack of face-to-face meeting time with mentees and/or a lack of advocacy on the mentees’ behalf. Meanwhile, the active forms occur when the mentor exhibits self-serving behaviors. These can include listing themselves as first author on a mentee’s project or discouraging a mentee from working with other mentors. Mentors must be able to self-check, seek feedback from mentees, and encourage mentees to further their professional networks beyond the boundaries of what the mentor alone can offer. Doing so helps create new opportunities and helps ensure a mutually beneficial relationship.

A great initial step to prevent passive and active mentorship malpractice is to leverage the benefits of team mentorship.^2,3 At its core, team mentorship capitalizes on the collective contributions of multiple mentors. Doing so not only provides security during uncertain times, but also allows for a diversity of perspectives, distribution of workload among mentors, and additional support for mentees.^3,4 Team mentorship it is particularly important during this current global health crisis, and such an approach from the outset could have significantly improved the scenario above.

For the above scenario, likely a transition in mentorship would be needed. Such transitions, whether short term or long term, require transparency, honesty, and willingness to engage in difficult conversations with mentees. Whether the mentor in the above case engages another faculty to take on the mentees or chooses to find a colleague who will agree to take on other competing demands, it will require time, effort, and energy – all of which are in short supply. When team mentorship is established from the outset, such transitions of mentorship can occur seamlessly and with more ease for all.

Additional considerations for successful mentoring of medical students or early-career physicians include understanding generational differences between the mentor and their mentees. As outlined by Waljee and colleagues, the next generation of trainees and physicians may act in ways that deviate from the norms of academic medicine’s tradition. As a mentor, it is imperative to understand these actions are not intended to disrupt the traditions and norms of health systems.⁵ For example, the use of technology during rounds can often be misconstrued as disrespectful. However, the underlying intent in many cases is to answer a question or access a helpful reference.

Seeing behavior and actions from the perspective of the mentee is one of the many ways to support and sustain successful mentoring relationships. A mindful approach benefits both mentees and mentors; this includes reflecting on the underlying motives for mentorship and cultivating gratitude for the relationships formed.⁶ While these steps may seem trivial, gratitude promotes happiness, trust, motivation, and respect. It can be felt by others, including mentees.

As mentors continue to shape the future, they have an ethical obligation to care for themselves, in addition to their mentees. In addition to avoiding mentorship malpractice, engaging in team mentorship, and incorporating mindful mentoring, an emphasis on self-care is critical.⁷ Taking time to recharge is essential. It allows one to be fully present, while also setting an example for the mentee. Explicitly addressing self-care for both mentor and mentee is a part of mindful mentorship, with benefits for all.⁶
 

Three key points:

1. Awareness of mentorship malpractice

2. Importance of team mentorship

3. Benefits of mindful mentorship

Mr. Rodoni is with the University of Michigan Medical School and Stephen M. Ross School of Business, Ann Arbor, Mich. Dr. Fessel is a professor of radiology in the department of radiology at Michigan Medicine, Ann Arbor. They reported having no disclosures relevant to this article.

References:

1. Chopra V et al. JAMA Intern Med. 2018 Feb;178:175-6.

2. Chopra V et al. JAMA. 2016 Apr 12;315:1453-4.

3. Chopra V et al. The Mentoring Guide: Helping Mentors & Mentees Succeed. Ann Arbor: Michigan Publishing, 2019.

4. Rodoni BM et al. Annals of Surgery. 2020 Aug;272(2):e151-2.

5. Waljee JF et al. JAMA. 2018 Apr 17;319(15):1547-8.

6. Chopra V and Saint S. Healthc (Amst). 2020 Mar;8(1):100390.

7. Fessell D et al. “Mentoring During a Crisis.” Harvard Business Review. 2020 Oct 29.

Although readers will be forgiven for missing the subtle change, the tables in the 2020 State of Hospital Medicine (SoHM) Report underwent a landmark structural change that echoes the growth of our field. In the latest SoHM Report, the hospital medicine group (HMG) size categories all increased significantly to reflect the fact that hospitalist groups have grown from a median of 9 physician full time equivalents (FTE) in 2016 to a median of 15.2 employed/contracted FTE (excluding FTE provided by locum tenens providers) in 2020.

For many years, the Report considered “large” adult HMGs to be those with 30 or more FTE of physicians, and smaller groups were organized by FTE categories of <5, 5-9, 10-19, and 20-29. Now the SoHM Report describes a large HMG as 50 employed/contracted FTE or greater, a category that represents 12.7% of HMGs serving adults. The other categories expanded to <5, 5-14, 15-29, and 30-49, respectively. Overall, HMGs are growing in size, and the SoHM displays new data slices that help leaders to compare their group to modern peers.

There are some caveats to consider. First, these figures only represent physician FTE, and essentially all these large groups employ NP/PA hospitalists as well. Second, these HMGs typically employ some part-time and contracted PRN physicians in this FTE count. In combination, these two factors mean that large HMGs often employ many more than 50 individual clinicians. In fact, the average number of physicians in this cohort was 72.3 before counting NP/PAs and locums. Third, do not interpret the portion of large groups in the survey (12.7%) as insignificant. Because each one employs so many total hospitalists, large HMGs collectively represent a common work environment for many hospitalists in the US. Lastly, although pediatric HMGs have grown, far fewer (3.1%) have over 50 FTE, so this column focuses on HMGs serving adults.

Why does it matter that groups are growing in size? The SoHM Report offers extensive data to answer this question. Here are a couple of highlights but consider buying the report to dig deeper. First, large groups are far more likely to offer variable scheduling. Although the 7-on, 7-off scheduling pattern is still the norm in all group sizes, large HMGs are most likely to offer something flexible that might enhance career sustainability for hospitalists. Second, large groups are the most likely to employ a few hospitalists with extra training, whether that be geriatrics, palliative care, pediatrics, or a medicine subspecialty. Working in a large group means you can ask for curbside consults from a diverse and well-trained bunch of colleagues. Third, large groups were most likely to employ nocturnists, meaning fewer night shifts are allocated to the hospitalists who want to focus on daytime work. From an individual perspective, there is a lot to like about working in a large HMG.

There are some drawbacks to larger groups, of course. Large groups can be less socially cohesive and the costs of managing 70-100 hospitalists typically grow well past the capacity of a single group leader. My personal belief is that these downsides can be solved through economies of scale and skilled management teams. In addition, a large group can afford to dedicate leadership FTE to niche hospitalist needs, such as career development and coaching, which are difficult to fund in small practices. This also provides more opportunities for staff hospitalists to begin taking on some leadership or administrative duties or branch out into related areas such as quality improvement, case management physician advisor roles, or IT expertise.

Ultimately, large groups typically represent the maturation of an HMG within a large hospital – it signifies that the hospital relies on that group to deliver great patient outcomes in every corner of the hospital. Where you practice remains a personal choice, but the emergence of large groups hints at the clout and sophistication hospitalists can build by banding together. Learn more about the full 2020 SoHM Report at hospitalmedicine.org/sohm.
 

Dr. White is associate professor of medicine at the University of Washington, Seattle. He is the chair of SHM’s Practice Analysis Committee.

Although readers will be forgiven for missing the subtle change, the tables in the 2020 State of Hospital Medicine (SoHM) Report underwent a landmark structural change that echoes the growth of our field. In the latest SoHM Report, the hospital medicine group (HMG) size categories all increased significantly to reflect the fact that hospitalist groups have grown from a median of 9 physician full time equivalents (FTE) in 2016 to a median of 15.2 employed/contracted FTE (excluding FTE provided by locum tenens providers) in 2020.

For many years, the Report considered “large” adult HMGs to be those with 30 or more FTE of physicians, and smaller groups were organized by FTE categories of <5, 5-9, 10-19, and 20-29. Now the SoHM Report describes a large HMG as 50 employed/contracted FTE or greater, a category that represents 12.7% of HMGs serving adults. The other categories expanded to <5, 5-14, 15-29, and 30-49, respectively. Overall, HMGs are growing in size, and the SoHM displays new data slices that help leaders to compare their group to modern peers.

There are some caveats to consider. First, these figures only represent physician FTE, and essentially all these large groups employ NP/PA hospitalists as well. Second, these HMGs typically employ some part-time and contracted PRN physicians in this FTE count. In combination, these two factors mean that large HMGs often employ many more than 50 individual clinicians. In fact, the average number of physicians in this cohort was 72.3 before counting NP/PAs and locums. Third, do not interpret the portion of large groups in the survey (12.7%) as insignificant. Because each one employs so many total hospitalists, large HMGs collectively represent a common work environment for many hospitalists in the US. Lastly, although pediatric HMGs have grown, far fewer (3.1%) have over 50 FTE, so this column focuses on HMGs serving adults.

Why does it matter that groups are growing in size? The SoHM Report offers extensive data to answer this question. Here are a couple of highlights but consider buying the report to dig deeper. First, large groups are far more likely to offer variable scheduling. Although the 7-on, 7-off scheduling pattern is still the norm in all group sizes, large HMGs are most likely to offer something flexible that might enhance career sustainability for hospitalists. Second, large groups are the most likely to employ a few hospitalists with extra training, whether that be geriatrics, palliative care, pediatrics, or a medicine subspecialty. Working in a large group means you can ask for curbside consults from a diverse and well-trained bunch of colleagues. Third, large groups were most likely to employ nocturnists, meaning fewer night shifts are allocated to the hospitalists who want to focus on daytime work. From an individual perspective, there is a lot to like about working in a large HMG.

There are some drawbacks to larger groups, of course. Large groups can be less socially cohesive and the costs of managing 70-100 hospitalists typically grow well past the capacity of a single group leader. My personal belief is that these downsides can be solved through economies of scale and skilled management teams. In addition, a large group can afford to dedicate leadership FTE to niche hospitalist needs, such as career development and coaching, which are difficult to fund in small practices. This also provides more opportunities for staff hospitalists to begin taking on some leadership or administrative duties or branch out into related areas such as quality improvement, case management physician advisor roles, or IT expertise.

Ultimately, large groups typically represent the maturation of an HMG within a large hospital – it signifies that the hospital relies on that group to deliver great patient outcomes in every corner of the hospital. Where you practice remains a personal choice, but the emergence of large groups hints at the clout and sophistication hospitalists can build by banding together. Learn more about the full 2020 SoHM Report at hospitalmedicine.org/sohm.
 

Dr. White is associate professor of medicine at the University of Washington, Seattle. He is the chair of SHM’s Practice Analysis Committee.

Although readers will be forgiven for missing the subtle change, the tables in the 2020 State of Hospital Medicine (SoHM) Report underwent a landmark structural change that echoes the growth of our field. In the latest SoHM Report, the hospital medicine group (HMG) size categories all increased significantly to reflect the fact that hospitalist groups have grown from a median of 9 physician full time equivalents (FTE) in 2016 to a median of 15.2 employed/contracted FTE (excluding FTE provided by locum tenens providers) in 2020.

For many years, the Report considered “large” adult HMGs to be those with 30 or more FTE of physicians, and smaller groups were organized by FTE categories of <5, 5-9, 10-19, and 20-29. Now the SoHM Report describes a large HMG as 50 employed/contracted FTE or greater, a category that represents 12.7% of HMGs serving adults. The other categories expanded to <5, 5-14, 15-29, and 30-49, respectively. Overall, HMGs are growing in size, and the SoHM displays new data slices that help leaders to compare their group to modern peers.

There are some caveats to consider. First, these figures only represent physician FTE, and essentially all these large groups employ NP/PA hospitalists as well. Second, these HMGs typically employ some part-time and contracted PRN physicians in this FTE count. In combination, these two factors mean that large HMGs often employ many more than 50 individual clinicians. In fact, the average number of physicians in this cohort was 72.3 before counting NP/PAs and locums. Third, do not interpret the portion of large groups in the survey (12.7%) as insignificant. Because each one employs so many total hospitalists, large HMGs collectively represent a common work environment for many hospitalists in the US. Lastly, although pediatric HMGs have grown, far fewer (3.1%) have over 50 FTE, so this column focuses on HMGs serving adults.

Why does it matter that groups are growing in size? The SoHM Report offers extensive data to answer this question. Here are a couple of highlights but consider buying the report to dig deeper. First, large groups are far more likely to offer variable scheduling. Although the 7-on, 7-off scheduling pattern is still the norm in all group sizes, large HMGs are most likely to offer something flexible that might enhance career sustainability for hospitalists. Second, large groups are the most likely to employ a few hospitalists with extra training, whether that be geriatrics, palliative care, pediatrics, or a medicine subspecialty. Working in a large group means you can ask for curbside consults from a diverse and well-trained bunch of colleagues. Third, large groups were most likely to employ nocturnists, meaning fewer night shifts are allocated to the hospitalists who want to focus on daytime work. From an individual perspective, there is a lot to like about working in a large HMG.

There are some drawbacks to larger groups, of course. Large groups can be less socially cohesive and the costs of managing 70-100 hospitalists typically grow well past the capacity of a single group leader. My personal belief is that these downsides can be solved through economies of scale and skilled management teams. In addition, a large group can afford to dedicate leadership FTE to niche hospitalist needs, such as career development and coaching, which are difficult to fund in small practices. This also provides more opportunities for staff hospitalists to begin taking on some leadership or administrative duties or branch out into related areas such as quality improvement, case management physician advisor roles, or IT expertise.

Ultimately, large groups typically represent the maturation of an HMG within a large hospital – it signifies that the hospital relies on that group to deliver great patient outcomes in every corner of the hospital. Where you practice remains a personal choice, but the emergence of large groups hints at the clout and sophistication hospitalists can build by banding together. Learn more about the full 2020 SoHM Report at hospitalmedicine.org/sohm.
 

Dr. White is associate professor of medicine at the University of Washington, Seattle. He is the chair of SHM’s Practice Analysis Committee.