Women's Health

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

If the goal of a clinical encounter is to identify issues that adversely affect health, well-being, and life satisfaction, open-ended questions on sexual problems are essential, according to an expert who provided tips during a session presented by Current Psychiatry and the American Academy of Clinical Psychiatrists about how to begin a productive dialogue.

For identifying and treating the obstacles to sexual health, “the onus is on the provider,” said Anita H. Clayton, MD, chair of psychiatry and neurobehavioral sciences at the University of Virginia, Charlottesville.

In a poll published more than 20 years ago, 91% of men and 84% of women reported that a satisfying sex life is important, while 90% agreed that sexual difficulties cause emotional problems, said Dr. Clayton, who sees no reason to think that those percentages have changed. Yet, patients are traditionally reluctant to raise their concerns about sexual issues to a physician.

In the same poll, about 50% of the respondents characterized themselves as “very concerned” that a clinician would simply dismiss a sexual complaint or that there would be no treatment. Of the other respondents, 40% were somewhat concerned. Dr. Clayton assumes that those numbers are still valid and that they provide the rationale for asking routinely about sexual health, she said at the virtual meeting, presented by MedscapeLive.
 

Raising sexual health issues

“The clinician has to initiate the discussion and make it part of the routine examination,” said Dr. Clayton, also a professor of obstetrics and gynecology at the university. She indicated that unresolved sexual issues are a common and important but treatable problem, whether the underlying issue has a medical or psychological origin.

Yet, language is critical. Many physicians might have no difficulty discussing sexual problems, but patients often do. Dr. Clayton recommended developing strategies that might it easy if not seamless to elicit information about sexual health in the context of inquiring about other clinical issues.

“Use bridging statements,” Dr. Clayton suggested.

Bridging statements allow an easy transition into a discussion of sexual function from another clinical issue, Dr. Clayton said. As examples, she suggested moving to questions about sex from inquiries about conditions, such as diabetes, or medications, such as antidepressants, that are known to have an impact on sexual dysfunction.

Avoid yes-no questions.

To prompt a dialogue, Dr. Clayton advised against using yes-no questions that allow the patient to quickly dismiss the topic with a negative response. She tries to frame a question that requires a complete thought. In an inquiry addressed to a patient with diabetes, for example, she might first inform the patient that sexual issues are common with this disorder and then ask what types of sexual issues the patient is experiencing.

Once the topic is raised, a checklist approach is appropriate. Patients might be more or less willing to talk any one of the range of issues that influence sexual health, ranging from issues of desire and arousal to discomfort or pain. The door should be opened to a discussion of specific sexual organ function, such as ability to achieve an erection or adequate lubrication.

“Do not assume the patient is heterosexual,” Dr. Clayton cautioned.

It is reasonable and appropriate to bring up sexual health during the intake history. A discussion of sexual health can be initiated by simply posing the question: “Are you sexually active?” Importantly, Dr. Clayton strongly recommended a follow-up question when adults reply that they are not sexually active.

“If a patient is not sexually active, you should ask why,” Dr. Clayton said. The answer might involve a treatable condition.

In the ELIXIR study, which evaluated sexual function in patients with depression, more than twice as many patients reported impairments when asked by the physician than who volunteered this information spontaneously, according to Dr. Clayton, citing a study that found sexual issues in more than 70% of the 4,557 participants.

Prioritize choice of language.

Once sexual impairments are uncovered, clinicians will need to determine how to intervene, but Dr. Clayton recommended using clear and frank language to define the problem even if the language is tailored to the patient’s comfort level. Patients should be encouraged to recognize that there are solutions for most problems, but clinicians should recognize and respect cultural issues in directing patients toward solutions.

Dr. Clayton is not alone in recommending that patients be asked routinely about sexual health. Margot Savoy, MD, MPH, chair of family and community medicine, Temple University, Philadelphia, has also advocated for a proactive approach.

“Patients deserve whole-patient care that includes sexual health,” said Dr. Savoy, who was coauthor of a recent article that also outlined techniques for eliciting a sexual history.

She suggested that the need to inquire should not be considered age specific.

“Asking patients about their sexual history and concerns is a critical part of routine primary care across the lifespan,” she said.

“We also need to intentionally create a safe environment where it is as normal to talk about sexual questions or concerns as it is about how to care for a cold or manage a backache,” she added.

MedscapeLive and this news organization are owned by the same company. Dr. Clayton disclosed financial relationships with Acadia, Alkermes, Allergan, AMAG, Astellas, Fabre-Kramer, Janssen, Ovoca Bio, PureTech Health, Relmada, S1 Biopharma, Safe Therapeutics, Takeda, and WCG MedAd-vante-Prophase. Dr. Savoy reported no conflicts of interest.

If the goal of a clinical encounter is to identify issues that adversely affect health, well-being, and life satisfaction, open-ended questions on sexual problems are essential, according to an expert who provided tips during a session presented by Current Psychiatry and the American Academy of Clinical Psychiatrists about how to begin a productive dialogue.

For identifying and treating the obstacles to sexual health, “the onus is on the provider,” said Anita H. Clayton, MD, chair of psychiatry and neurobehavioral sciences at the University of Virginia, Charlottesville.

In a poll published more than 20 years ago, 91% of men and 84% of women reported that a satisfying sex life is important, while 90% agreed that sexual difficulties cause emotional problems, said Dr. Clayton, who sees no reason to think that those percentages have changed. Yet, patients are traditionally reluctant to raise their concerns about sexual issues to a physician.

In the same poll, about 50% of the respondents characterized themselves as “very concerned” that a clinician would simply dismiss a sexual complaint or that there would be no treatment. Of the other respondents, 40% were somewhat concerned. Dr. Clayton assumes that those numbers are still valid and that they provide the rationale for asking routinely about sexual health, she said at the virtual meeting, presented by MedscapeLive.
 

Raising sexual health issues

“The clinician has to initiate the discussion and make it part of the routine examination,” said Dr. Clayton, also a professor of obstetrics and gynecology at the university. She indicated that unresolved sexual issues are a common and important but treatable problem, whether the underlying issue has a medical or psychological origin.

Yet, language is critical. Many physicians might have no difficulty discussing sexual problems, but patients often do. Dr. Clayton recommended developing strategies that might it easy if not seamless to elicit information about sexual health in the context of inquiring about other clinical issues.

“Use bridging statements,” Dr. Clayton suggested.

Bridging statements allow an easy transition into a discussion of sexual function from another clinical issue, Dr. Clayton said. As examples, she suggested moving to questions about sex from inquiries about conditions, such as diabetes, or medications, such as antidepressants, that are known to have an impact on sexual dysfunction.

Avoid yes-no questions.

To prompt a dialogue, Dr. Clayton advised against using yes-no questions that allow the patient to quickly dismiss the topic with a negative response. She tries to frame a question that requires a complete thought. In an inquiry addressed to a patient with diabetes, for example, she might first inform the patient that sexual issues are common with this disorder and then ask what types of sexual issues the patient is experiencing.

Once the topic is raised, a checklist approach is appropriate. Patients might be more or less willing to talk any one of the range of issues that influence sexual health, ranging from issues of desire and arousal to discomfort or pain. The door should be opened to a discussion of specific sexual organ function, such as ability to achieve an erection or adequate lubrication.

“Do not assume the patient is heterosexual,” Dr. Clayton cautioned.

It is reasonable and appropriate to bring up sexual health during the intake history. A discussion of sexual health can be initiated by simply posing the question: “Are you sexually active?” Importantly, Dr. Clayton strongly recommended a follow-up question when adults reply that they are not sexually active.

“If a patient is not sexually active, you should ask why,” Dr. Clayton said. The answer might involve a treatable condition.

In the ELIXIR study, which evaluated sexual function in patients with depression, more than twice as many patients reported impairments when asked by the physician than who volunteered this information spontaneously, according to Dr. Clayton, citing a study that found sexual issues in more than 70% of the 4,557 participants.

Prioritize choice of language.

Once sexual impairments are uncovered, clinicians will need to determine how to intervene, but Dr. Clayton recommended using clear and frank language to define the problem even if the language is tailored to the patient’s comfort level. Patients should be encouraged to recognize that there are solutions for most problems, but clinicians should recognize and respect cultural issues in directing patients toward solutions.

Dr. Clayton is not alone in recommending that patients be asked routinely about sexual health. Margot Savoy, MD, MPH, chair of family and community medicine, Temple University, Philadelphia, has also advocated for a proactive approach.

“Patients deserve whole-patient care that includes sexual health,” said Dr. Savoy, who was coauthor of a recent article that also outlined techniques for eliciting a sexual history.

She suggested that the need to inquire should not be considered age specific.

“Asking patients about their sexual history and concerns is a critical part of routine primary care across the lifespan,” she said.

“We also need to intentionally create a safe environment where it is as normal to talk about sexual questions or concerns as it is about how to care for a cold or manage a backache,” she added.

MedscapeLive and this news organization are owned by the same company. Dr. Clayton disclosed financial relationships with Acadia, Alkermes, Allergan, AMAG, Astellas, Fabre-Kramer, Janssen, Ovoca Bio, PureTech Health, Relmada, S1 Biopharma, Safe Therapeutics, Takeda, and WCG MedAd-vante-Prophase. Dr. Savoy reported no conflicts of interest.

If the goal of a clinical encounter is to identify issues that adversely affect health, well-being, and life satisfaction, open-ended questions on sexual problems are essential, according to an expert who provided tips during a session presented by Current Psychiatry and the American Academy of Clinical Psychiatrists about how to begin a productive dialogue.

For identifying and treating the obstacles to sexual health, “the onus is on the provider,” said Anita H. Clayton, MD, chair of psychiatry and neurobehavioral sciences at the University of Virginia, Charlottesville.

In a poll published more than 20 years ago, 91% of men and 84% of women reported that a satisfying sex life is important, while 90% agreed that sexual difficulties cause emotional problems, said Dr. Clayton, who sees no reason to think that those percentages have changed. Yet, patients are traditionally reluctant to raise their concerns about sexual issues to a physician.

In the same poll, about 50% of the respondents characterized themselves as “very concerned” that a clinician would simply dismiss a sexual complaint or that there would be no treatment. Of the other respondents, 40% were somewhat concerned. Dr. Clayton assumes that those numbers are still valid and that they provide the rationale for asking routinely about sexual health, she said at the virtual meeting, presented by MedscapeLive.
 

Raising sexual health issues

“The clinician has to initiate the discussion and make it part of the routine examination,” said Dr. Clayton, also a professor of obstetrics and gynecology at the university. She indicated that unresolved sexual issues are a common and important but treatable problem, whether the underlying issue has a medical or psychological origin.

Yet, language is critical. Many physicians might have no difficulty discussing sexual problems, but patients often do. Dr. Clayton recommended developing strategies that might it easy if not seamless to elicit information about sexual health in the context of inquiring about other clinical issues.

“Use bridging statements,” Dr. Clayton suggested.

Bridging statements allow an easy transition into a discussion of sexual function from another clinical issue, Dr. Clayton said. As examples, she suggested moving to questions about sex from inquiries about conditions, such as diabetes, or medications, such as antidepressants, that are known to have an impact on sexual dysfunction.

Avoid yes-no questions.

To prompt a dialogue, Dr. Clayton advised against using yes-no questions that allow the patient to quickly dismiss the topic with a negative response. She tries to frame a question that requires a complete thought. In an inquiry addressed to a patient with diabetes, for example, she might first inform the patient that sexual issues are common with this disorder and then ask what types of sexual issues the patient is experiencing.

Once the topic is raised, a checklist approach is appropriate. Patients might be more or less willing to talk any one of the range of issues that influence sexual health, ranging from issues of desire and arousal to discomfort or pain. The door should be opened to a discussion of specific sexual organ function, such as ability to achieve an erection or adequate lubrication.

“Do not assume the patient is heterosexual,” Dr. Clayton cautioned.

It is reasonable and appropriate to bring up sexual health during the intake history. A discussion of sexual health can be initiated by simply posing the question: “Are you sexually active?” Importantly, Dr. Clayton strongly recommended a follow-up question when adults reply that they are not sexually active.

“If a patient is not sexually active, you should ask why,” Dr. Clayton said. The answer might involve a treatable condition.

In the ELIXIR study, which evaluated sexual function in patients with depression, more than twice as many patients reported impairments when asked by the physician than who volunteered this information spontaneously, according to Dr. Clayton, citing a study that found sexual issues in more than 70% of the 4,557 participants.

Prioritize choice of language.

Once sexual impairments are uncovered, clinicians will need to determine how to intervene, but Dr. Clayton recommended using clear and frank language to define the problem even if the language is tailored to the patient’s comfort level. Patients should be encouraged to recognize that there are solutions for most problems, but clinicians should recognize and respect cultural issues in directing patients toward solutions.

Dr. Clayton is not alone in recommending that patients be asked routinely about sexual health. Margot Savoy, MD, MPH, chair of family and community medicine, Temple University, Philadelphia, has also advocated for a proactive approach.

“Patients deserve whole-patient care that includes sexual health,” said Dr. Savoy, who was coauthor of a recent article that also outlined techniques for eliciting a sexual history.

She suggested that the need to inquire should not be considered age specific.

“Asking patients about their sexual history and concerns is a critical part of routine primary care across the lifespan,” she said.

“We also need to intentionally create a safe environment where it is as normal to talk about sexual questions or concerns as it is about how to care for a cold or manage a backache,” she added.

MedscapeLive and this news organization are owned by the same company. Dr. Clayton disclosed financial relationships with Acadia, Alkermes, Allergan, AMAG, Astellas, Fabre-Kramer, Janssen, Ovoca Bio, PureTech Health, Relmada, S1 Biopharma, Safe Therapeutics, Takeda, and WCG MedAd-vante-Prophase. Dr. Savoy reported no conflicts of interest.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

Women who were Black, Latina, American Indian, or Alaska Native were significantly less likely than White women to receive guidelines-adherent treatment for endometrial cancer, based on data from more than 80,000 women.

The incidence of uterine cancer has increased across all ethnicities in recent decades, and adherence to the National Comprehensive Cancer Network treatment guidelines has been associated with improved survival, wrote Victoria A. Rodriguez, MSW, MPH, of the University of California, Irvine, and colleagues. “To date, however, there are few studies that have looked at endometrial cancer disparities with adherence to National Comprehensive Cancer Network treatment guidelines.”

In a retrospective study published in Obstetrics & Gynecology, the researchers used data from the SEER (Surveillance, Epidemiology, and End Results) database between Jan. 1, 2006, and Dec. 31, 2015. The study population included 83,883 women aged 18 years and older who were diagnosed with their first or only endometrial carcinoma. The primary dependent variable was adherence to the NCCN guidelines for the initial course of treatment, which included a combination of therapies based on cancer subtype and the extent of the disease, the researchers said.

The researchers combined the guidelines and the corresponding data from the SEER database to create “a binary variable representing adherence to [NCCN] guidelines (1 = adherent treatment, 0 = nonadherent treatment).”

Approximately 60% of the total patient population received guidelines-adherent treatment. In a multivariate analysis, Black women, Latina women, and American Indian or Alaska Native women were significantly less likely than White women to receive such treatment (odds ratios, 0.88, 0.92, and 0.82, respectively), controlling for factors including neighborhood socioeconomic status, age, and stage at diagnosis, year of diagnosis, histology, and disease grade. Asian women and Native Hawaiian/Pacific Islander women were significantly more likely to received guidelines-adherent treatment, compared with White women (OR, 1.14 and 1.19, respectively).

The researchers also found a significant gradient in guidelines-adherent treatment based on neighborhood socioeconomic status. Relative to the highest neighborhood socioeconomic status group, women in the lower groups had significantly lower odds of receiving guidelines-adherent treatment, with ORs of 0.89, 0.84, 0.80, and 0.73, respectively, for the high-middle neighborhood socioeconomic group, the middle group, the low-middle group, and the lowest group (P < .001 for all).

“Our study is novel in that it examines neighborhood socioeconomic disparities in the understudied context of treatment adherence for endometrial cancer,” the researchers noted.

The study findings were limited by several factors in including the retrospective design and potential for unmeasured confounding variables not included in SEER, such as hospital and physician characteristics, the researchers said. Also, the SEER data set was limited to only the first course of treatment, and did not include information on patient comorbidities that might affect treatment.

“Future research should qualitatively explore reasons for nonadherent treatment within endometrial cancer and other cancer sites among various racial-ethnic groups and socioeconomic status groups, with special attention to low-income women of color,” the researchers emphasized. More research on the impact of comorbidities on a patient’s ability to receive guidelines-based care should be used to inform whether comorbidities should be part of the NCCN guidelines.

However, the results were strengthened by the large sample size and diverse population, so the findings are generalizable to the overall U.S. population, the researchers said.

“Interventions are needed to ensure that equitable cancer treatment practices are available for all individuals regardless of their racial-ethnic or socioeconomic backgrounds,” they concluded.
 

Pursue optimal treatment to curb mortality

Even more concerning than the increase in the incidence of endometrial cancer in the United States is the increase in mortality from this disease, said Emma C. Rossi, MD, of the University of North Carolina at Chapel Hill, in an interview.

“Therefore, it is critical that we identify factors which might be contributing to the increasing lethality of this cancer,” she emphasized. “One such potential factor is race, as it has been observed that Black race is associated with an increased risk of death from endometrial cancer. Historically, this was attributed to the more aggressive subtypes of endometrial cancer (such as serous) which have a higher incidence among Black women. However, more recently, population-based studies have identified that this worse prognosis is independent of histologic cell type,” which suggests that something in our health care delivery is contributing to these worse outcomes.

“The present study helps to confirm these concerning associations, shedding some light on contributory factors, in this case, modifiable (adherence to recommended guidelines) and less modifiable (neighborhood socioeconomic environments) [ones],” Dr. Rossi noted. “The guidelines that are established by the NCCN are chosen after they have been shown to be associated with improved outcomes (including either survival or quality of life), and therefore lack of adherence to these outcomes may suggest inferior quality care is being delivered.”

Studies such as this are helpful in exposing the problem of treatment disparity to help identify sources of problems to develop solutions, she added.

The results should inspire clinicians “to feel agency in changing these outcomes, albeit by tackling very difficult social, political, and health system shortfalls,” she said.
 

Identify barriers to care

Barriers to greater adherence to guidelines-based care include varying definitions of such care, Dr. Rossi said.

“This is particularly true for surgical management of endometrial cancer, which remains controversial with respect to lymph node assessment. Lack of surgical staging with lymph node assessment was considered noncompliant care for this study; however, lymphadenectomy has not specifically, in and of itself, been associated with improved outcomes, and therefore some surgeons argue against performing it routinely,” she explained.

“Lack of access to sophisticated surgical tools and advanced surgical techniques may account for nonguidelines-based care in the patients with early-stage endometrial cancer; however, there are likely other differences in the ability to deliver guideline-concordant care (such as chemotherapy and radiation therapy) for advanced-stage cancers,” Dr. Rossi said. “Patient and provider positive attitudes toward adjuvant therapy, access to transportation, supportive home environments, paid sick leave, well-controlled or minimal comorbidities are all factors which promote the administration of complex adjuvant therapies such as chemotherapy and radiation. In low-resource neighborhoods and minority communities, barriers to these factors may be contributing to nonguidelines-concordant care.”

Dr. Rossi emphasized the need to “dive deeper into these data at individual health-system and provider levels.” For example, research is needed to compare the practice patterns and models of high-performing clinical practices with lower-performing practices in terms of factors such as tumor boards, journal review, peer review, dashboards, and metrics. By doing so, “we can ensure that we are understanding where and why variations in care are occurring,” Dr. Rossi said.

The study was supported in part by the Faculty Mentor Program Fellowship from the University of California, Irvine, graduate division. Ms. Rodriguez was supported in part by a grant from the National Cancer Institute. The researchers had no financial conflicts to disclose. Dr. Rossi had no financial conflicts to disclose.

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

Using high-intensity focused electromagnetic (HIFEM) technology to strengthen pelvic floor muscles for the improvement of urinary incontinence (UI) and female sexual function was safe and effective at 9 months follow-up, results from a multicenter study showed.

“The pelvic floor consists of three pairs of muscles: the pubococcygeus, the iliococcygeus, and the puborectalis,” lead study author Joseph Berenholz, MD, and a diplomate of the American Board of Obstetics & Gynecology, said during the annual conference of the American Society for Laser Medicine and Surgery. “They control continence through support of pelvic organs. The urethra, the vagina, and the rectum pass through that diaphragm. It also contributes to sexual sensation and arousal. A deconditioning of the pelvic floor is usually the result of child-bearing years or aging, which usually results in urinary incontinence and impairment of sexual function. The noninvasive strengthening of the pelvic floor muscles helps to regain muscle tone and strength.”

In a prospective, open-label, single-arm study conducted at four sites, Dr. Berenholz, medical director of the Michigan Center for Women’s Health in Farmington Hills, and colleagues investigated the long-term effectiveness of HIFEM-induced pelvic floor muscle (PFM) strengthening for improvement of UI and sexual function. HIFEM selectively targets neuromuscular tissue and induces supramaximal PFM contractions that cannot be achieved voluntarily, he said, causing muscle strengthening due to muscle fiber hypertrophy, which helps patients to better isolate and command their muscles.

The study population consisted of 33 females with a mean age of 49 years who had UI and UI-related problems in sexual life. They received six 28-minute HIFEM treatments of the pelvic floor with the BTL Emsella, which is FDA cleared for both stress and urge incontinence. The frequency of visits was two treatments per week and the intensity of HIFEM was adjusted between 0% and 100% based on the patient’s tolerance threshold. Evaluations were conducted at baseline, after the last treatment, at 1, 3, 6, and 9 months. The primary outcomes were change in urine leakage based on the International Consultation on Incontinence Questionnaire–Short Form (ICIQ-UI-SF) and change in sexual function based on the Female Sexual Function Index (FSFI) and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Secondary endpoints were adverse events and the comfort of therapy based on a 7-point Likert scale.

Dr. Berenholz reported that from baseline the severity of UI based on the ICIQ-SF significantly decreased 60% by a mean of 8.1 points between baseline and 9 months (P < .001). At 1 month, the FSFI score improved 32% by a mean of 7.1 points (P < .001) and was sustained throughout the study. The most prominent changes were seen in the subdomains of desire, arousal, lubrication, and orgasm response.

The PISQ-12 score incrementally increased 25% to a mean improvement of 8.2 points at 9 months (P < .001). Subjects improved most in the emotive subdomain, reporting more frequent orgasms, increased desire, and sexual excitement. The minimal important difference was 6 points.

“This is a true paradigm shift in the treatment of incontinence and sexual dysfunction,” Dr. Berenholz said. “The therapy was safe, comfortable, no adverse events emerged, and 31 subjects (94%) described the therapy as comfortable. Interim data suggest that treatment effect was maintained for 9 months, and there were no significant declines in scores in the long term. The upcoming 12-month follow-up data will let us know if more maintenance therapy is needed.”

During a question-and-answer session, one of the abstract section chairs, Albert Wolkerstorfer, MD, PhD, wondered about the potential for combination treatments in this patient population. “I can imagine that something that is working on the muscle tone has a totally different mechanism than something that is working on the mucosa and the underlying tissue without really affecting the muscle,” said Dr. Wolkerstorfer, a dermatologist at the Netherlands Institute for Pigment Disorders, department of dermatology, University of Amsterdam. “Would a combination be the way to go?”

Dr. Berenholz said that he sometimes combines HIFEM with the ULTRA Femme 360, a radiofrequency thermal energy device. “We thought this addresses two issues,” he said. “One is fascial muscle, which is the underlying structural issue for incontinence. The other is thermal energy to aid in incontinence prevention by inducing production of elastin and collagen in the midurethra, but also to promote lubrication and heightened sensitivity in the patient who’s either menopausal or has undergone chemotherapy for breast cancer.”

Dr. Berenholz reported having no financial disclosures. Dr. Wolkerstorfer disclosed that he has received consulting fees from Lumenis and InCyte and equipment from Humeca and PerfAction Technologies. He has also received grant funding from Novartis and InCyte and he is a member of InCyte’s advisory board.

dbrunk@mdedge.com

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

If moderate to severe postpartum depression poses a risk to child development, that argues in favor of pharmacologic therapy, according to a detailed risk-benefit assessment presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

monkeybusinessimages/Thinkstock

“It is important to consider that there are potential risks of antidepressant drugs, but there are also potential risks from not providing effective treatment,” reported Neha Hudepohl, MD, at the virtual meeting, presented by MedscapeLive.

On a website maintained by the Centers for Disease Control and Prevention, the question of whether antidepressants pose a risk to breast-feeding children is answered with a “maybe.” Although many of these drugs can be detected in breast milk, according to the CDC, “most have little or no effect on milk supply or on infant well-being.”

This is enough uncertainty that antidepressants are not first-line intervention when postpartum depression is mild, said Dr. Hudepohl, director of women’s mental health at Prisma Health Upstate, Greenville, S.C. However, she noted that the American College of Obstetricians and Gynecologists is among the organizations that recommend drug treatment if symptoms are moderate to severe.

“Depression in the mother affects interactions in feeding practices, sleep routines and patterns, and safety practices,” said Dr. Hudepohl, citing published studies supporting each of these consequences.

For the child, there is some degree of uncertainty about risk from untreated maternal depression as well as from breast mild exposure to antidepressants. Conclusive statements are not offered by ACOG and others.

“Some but not all studies have shown an impact of either antenatal or postnatal depression on speech recognition in infancy of native versus nonnative languages, IQ, and cognitive development, and reduction in left frontal brain electrical activity associated with impaired positive emotions,” Dr. Hudepohl reported.

Sifting through published data, Dr. Hudepohl cited studies associating persistent postpartum depression with a more than fourfold risk of behavioral problems at the age of 3.5 years, lower grades in mathematics at age 16, and a higher prevalence of depression at age 18. Among children who had depressed mothers in infancy, there have also been studies showing a higher reactivity to stressors and higher baseline cortisol levels.

“The good news is that these effects in children appear to be largely reversible with maternal treatment,” Dr. Hudepohl said. In fact, she cited evidence of a correlation between improvement in maternal symptoms and a reduction in the complications in children, such as behavioral problems.

Postpartum depression, which can develop anytime in the first 12 months after childbirth, is not uncommon, occurring in approximately 15% of women, according to Dr. Hudepohl. Risk factors include personal or family history of depression, anxiety or depression during pregnancy, and a prior history of postpartum depression.

Postpartum depression increases the risk of maternal suicide by about 70-fold, Dr. Hudepohl reported. She noted that the peaks in suicide attempts in the 1st and 12th month after delivery. Adverse infant outcomes are not a predictor of increase risk of attempts, but fetal or infant death are.

According to one study, about 40% of mothers with postpartum depression have intrusive thoughts that involve harming their child. About 15% fear being alone with their infant. Behaviors such as decreased playfulness, less talking, or other interactions with the child, and inconsistent response to the child are all likely to contribute to impaired maternal-child bonding, Dr. Hudepohl reported.

For women who discontinued antidepressants for pregnancy but have now developed significant postpartum depression, Dr. Hudepohl recommended using “what has worked in the past.” She considered monotherapy preferable if possible, but severe symptoms warrant more aggressive intervention. Dr. Hudepohl pointed out that the risks of antidepressants taken by the breast-feeding mother to the infant remain unclear despite multiple studies attempting to establish and quantify risk.

“Antidepressants are the most researched medication in pregnancy,” she said.

Conversely, the risks of untreated symptoms to the mother are significant, and the potential risks to the infant and family – if variable – are not insignificant.

Overall, “nonpharmacologic treatment is preferred first line for mild symptoms,” Dr. Hudepohl, but she and others consider a risk-benefit ratio growing increasingly in favor of drug therapy when this approach is the best option for bringing moderate to severe symptoms under control.

Whether depression arises during pregnancy or in the postpartum period, “psychotherapy is generally considered first-line treatment,” agreed Nancy Byatt, DO, MS, MBA, professor of psychiatry and of obstetrics and gynecology at the University of Massachusetts, Worcester.

Dr. Byatt, who has published frequently on this topic, further agreed that risks to the mother and the child increase with uncontrolled depression in the postpartum period. With symptoms of greater intensity, the uncertain risks of medication are outweighed by substantial potential benefits.

“When a pregnant or postpartum individual has moderate to severe illness, treatment with medication is typically recommended, because the benefits are thought to outweigh the risks,” she said, echoing a consensus opinion among experts and organized medicine.

MedscapeLive and this news organization are owned by the same parent company. Dr. Hudepohl and Dr. Byatt reported no potential financial conflicts of interest.
 

Diaphragmatic endometriosis is often diagnosed several years after the start of symptoms – mainly moderate to severe pain – and this is potentially because of general lack of awareness of diaphragmatic endometriosis among the general population and medical professionals.

Findings of the international survey that explored the diagnosis and treatment of diaphragmatic endometriosis were presented at this year’s Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress by medical student Rachel Piccus, MSc, based at the University of Birmingham (England). Robert Sutcliffe, MD, consultant in hepatobiliary and pancreatic surgery, at Queen Elizabeth Hospital Birmingham was senior author. Results were also published in the May 2021 issue of the European Journal of Obstetrics and Gynaecology and Reproductive Biology.

The study found that it took an average of five visits to a primary physician before referral to a gynecologist.

“Late diagnosis could also be due to the idea that diaphragmatic endometriosis symptoms often present before pelvic symptoms and therefore the site of pain is considered atypical for pelvic endometriosis,” Ms. Piccus said, adding that “clinicians are screening for cyclical pain, which is typical of endometriosis, but our study has shown that pain can in fact be more frequent – daily and weekly.”

These significant diagnostic delays, seen from the time of the initial primary care and gynecology consultation has the potential to significantly affect quality of life as seen in pelvic endometriosis, said Ms. Piccus. “These delays are partly due to a lack of awareness among gynecologists, but could also be due to pelvic laparoscopy being insufficient to examine the diaphragm behind the liver.”

Justin Clark, MD, consultant gynaecologist, Birmingham (England) Women’s and Children Hospital, moderated the session and agreed that the study highlights the need for greater awareness of this variant of endometriosis. “Whilst endometriosis affecting the diaphragm, subdiaphragm, and thorax is rare, the condition causes substantial morbidity.”

“Greater knowledge of thoracic endometriosis amongst clinicians in both primary and secondary care is needed to ensure accurate and timely diagnosis,” he added.

Diaphragmatic endometriosis is estimated to affect 1%-1.5% of all endometriosis patients and presents as cyclical pain in the chest, abdomen, and shoulder tip, as well as other respiratory symptoms such as catamenial pneumothorax and difficulty breathing.

“Cross-sectional imaging has shown low sensitivity so upper abdominal laparoscopy is the gold standard; however, this has implications for diagnostic delay because a strong clinical suspicion is required to refer for this invasive procedure,” explained Ms. Piccus referring to one of the reasons underpinning the need for the study.

When successfully diagnosed, treatment requires excision or ablation surgery and studies show symptomatic relief in 75%-100% of cases.

To gauge the extent of delayed diagnosis as well as treatment outcomes from a patient perspective, Ms. Piccus circulated an anonymous online survey among women with a previous history of surgery for diaphragmatic endometriosis.
 

Diaphragmatic endometriosis pain – daily and weekly as well as cyclical

A total of 137 participants responded to the survey, with a median age of 34 years (range, 19-53). Median age of diaphragmatic endometriosis onset was 27 years (range, 11-50), and importantly, diaphragmatic endometriosis symptoms started before pelvic symptoms in 90 respondents (66%).

The dominant symptom was pain. A total of 38% reported cyclical pain (related to endometrial shedding during menstruation), 15% weekly pain, and 47% daily pain, both of which were worse during the menstrual cycle. Furthermore, 14% reported other symptoms including catamenial pneumothorax, difficulty breathing, and hemoptysis.

“Whilst this cyclical pain is typical of endometriosis, we see that diagnostic delays may be due to misdiagnosis because clinicians are screening for this cyclical pain whilst our study has shown that pain can in fact be more frequent, being daily and weekly,” noted Ms. Piccus. Moderate to severe pain was reported in 67% of respondents and moderate in 31%, only 2% reported pain as mild.

Location of pain comprised moderate to severe pain in the upper abdomen (68%), chest (64%) and shoulder (54%). Pain was right-sided in 54%, left-sided in 11% and bilateral in 35%. Upper back and neck were also reported as sites of pain.

Indirectly providing a measure of the lack of awareness of diaphragmatic endometriosis on behalf of primary care, 122 participants reported initially visiting their primary care physician for help and 65 were given a diagnosis – in only 14 cases was that diaphragmatic endometriosis. There were a range of other gynecologic (e.g. ovarian cyst, two), respiratory (spontaneous pneumothorax, seven), gastrointestinal (gastritis/reflux, eight), musculoskeletal (six), and psychological (anxiety/stress, four) diagnoses.

A median of 5 primary care consultations (range, 1-100) were required before referral to a gynecologist, with 30% seeing a primary care physician over 10 times. A further 14 patients self-referred to gynecologist.

“These findings have implications for diagnostic delay, added Ms. Piccus. “While the majority of respondents were diagnosed less than a year from the first GP visit, the median delay was 2 years, with 31% diagnosed after 5 or more years. One took 23 years for an initial diagnosis.”

Most cases were diagnosed at the time of surgery – 93%, with 52% at pelvic laparoscopy, 35% upper abdominal laparoscopy, with 30% requiring two or more laparoscopies before they were diagnosed with diaphragmatic endometriosis. A total of 7% were diagnosed via cross-sectional imaging prior to surgery.
 

Treatment outcomes for diaphragmatic endometriosis

Reflecting the literature, surgery to remove the endometriosis lesions was mainly laparoscopic with 47% abdominal excisions, and 29% abdominal ablations; 6% received open abdominal procedures, and 18% received open thoracotomy or video-assisted thoracoscopic surgery.

The survey asked about postoperative symptoms 6 months after surgery and at the time of survey. Symptoms at 6 months post surgery had completely resolved in 18%, shown significant improvement in 48%, and no improvement in 20%. Worsening of symptoms was seen in 14%. Long-term pain was reported by 21% as severe, 27% as moderate, 35% as mild, and 17% had no symptoms.

Further findings included that 23% underwent additional procedures to treat their diaphragmatic endometriosis, and that there was no significant difference between excision and ablation, nor between age of onset of symptoms or length of diagnostic delay.

“Surgical treatment to remove these extra pelvic deposits of endometriosis will depend upon the type and distribution of thoracic endometriosis and a variety of surgical specialties may need to be involved including gynecologists, cardiothoracic, and upper gastrointestinal/liver surgeons,” Dr. Clark said.

He added that familiar hormonal medical treatments for more typical pelvic endometriosis should also be considered for primary and maintenance treatment. “These data suggest a high symptomatic recurrence rate after surgical treatment and so medical treatments should be considered to try and minimize the risks of endometriosis symptoms returning.”

Dr. Clark also pointed out that multidisciplinary clinical teams should be established in specialized centers to plan surgical and medical management to enhance clinical outcomes and collect data to better understand this enigmatic condition.

Ms. Piccus and Dr. Clark have no relevant conflicts of interest.

Diaphragmatic endometriosis is often diagnosed several years after the start of symptoms – mainly moderate to severe pain – and this is potentially because of general lack of awareness of diaphragmatic endometriosis among the general population and medical professionals.

Findings of the international survey that explored the diagnosis and treatment of diaphragmatic endometriosis were presented at this year’s Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress by medical student Rachel Piccus, MSc, based at the University of Birmingham (England). Robert Sutcliffe, MD, consultant in hepatobiliary and pancreatic surgery, at Queen Elizabeth Hospital Birmingham was senior author. Results were also published in the May 2021 issue of the European Journal of Obstetrics and Gynaecology and Reproductive Biology.

The study found that it took an average of five visits to a primary physician before referral to a gynecologist.

“Late diagnosis could also be due to the idea that diaphragmatic endometriosis symptoms often present before pelvic symptoms and therefore the site of pain is considered atypical for pelvic endometriosis,” Ms. Piccus said, adding that “clinicians are screening for cyclical pain, which is typical of endometriosis, but our study has shown that pain can in fact be more frequent – daily and weekly.”

These significant diagnostic delays, seen from the time of the initial primary care and gynecology consultation has the potential to significantly affect quality of life as seen in pelvic endometriosis, said Ms. Piccus. “These delays are partly due to a lack of awareness among gynecologists, but could also be due to pelvic laparoscopy being insufficient to examine the diaphragm behind the liver.”

Justin Clark, MD, consultant gynaecologist, Birmingham (England) Women’s and Children Hospital, moderated the session and agreed that the study highlights the need for greater awareness of this variant of endometriosis. “Whilst endometriosis affecting the diaphragm, subdiaphragm, and thorax is rare, the condition causes substantial morbidity.”

“Greater knowledge of thoracic endometriosis amongst clinicians in both primary and secondary care is needed to ensure accurate and timely diagnosis,” he added.

Diaphragmatic endometriosis is estimated to affect 1%-1.5% of all endometriosis patients and presents as cyclical pain in the chest, abdomen, and shoulder tip, as well as other respiratory symptoms such as catamenial pneumothorax and difficulty breathing.

“Cross-sectional imaging has shown low sensitivity so upper abdominal laparoscopy is the gold standard; however, this has implications for diagnostic delay because a strong clinical suspicion is required to refer for this invasive procedure,” explained Ms. Piccus referring to one of the reasons underpinning the need for the study.

When successfully diagnosed, treatment requires excision or ablation surgery and studies show symptomatic relief in 75%-100% of cases.

To gauge the extent of delayed diagnosis as well as treatment outcomes from a patient perspective, Ms. Piccus circulated an anonymous online survey among women with a previous history of surgery for diaphragmatic endometriosis.
 

Diaphragmatic endometriosis pain – daily and weekly as well as cyclical

A total of 137 participants responded to the survey, with a median age of 34 years (range, 19-53). Median age of diaphragmatic endometriosis onset was 27 years (range, 11-50), and importantly, diaphragmatic endometriosis symptoms started before pelvic symptoms in 90 respondents (66%).

The dominant symptom was pain. A total of 38% reported cyclical pain (related to endometrial shedding during menstruation), 15% weekly pain, and 47% daily pain, both of which were worse during the menstrual cycle. Furthermore, 14% reported other symptoms including catamenial pneumothorax, difficulty breathing, and hemoptysis.

“Whilst this cyclical pain is typical of endometriosis, we see that diagnostic delays may be due to misdiagnosis because clinicians are screening for this cyclical pain whilst our study has shown that pain can in fact be more frequent, being daily and weekly,” noted Ms. Piccus. Moderate to severe pain was reported in 67% of respondents and moderate in 31%, only 2% reported pain as mild.

Location of pain comprised moderate to severe pain in the upper abdomen (68%), chest (64%) and shoulder (54%). Pain was right-sided in 54%, left-sided in 11% and bilateral in 35%. Upper back and neck were also reported as sites of pain.

Indirectly providing a measure of the lack of awareness of diaphragmatic endometriosis on behalf of primary care, 122 participants reported initially visiting their primary care physician for help and 65 were given a diagnosis – in only 14 cases was that diaphragmatic endometriosis. There were a range of other gynecologic (e.g. ovarian cyst, two), respiratory (spontaneous pneumothorax, seven), gastrointestinal (gastritis/reflux, eight), musculoskeletal (six), and psychological (anxiety/stress, four) diagnoses.

A median of 5 primary care consultations (range, 1-100) were required before referral to a gynecologist, with 30% seeing a primary care physician over 10 times. A further 14 patients self-referred to gynecologist.

“These findings have implications for diagnostic delay, added Ms. Piccus. “While the majority of respondents were diagnosed less than a year from the first GP visit, the median delay was 2 years, with 31% diagnosed after 5 or more years. One took 23 years for an initial diagnosis.”

Most cases were diagnosed at the time of surgery – 93%, with 52% at pelvic laparoscopy, 35% upper abdominal laparoscopy, with 30% requiring two or more laparoscopies before they were diagnosed with diaphragmatic endometriosis. A total of 7% were diagnosed via cross-sectional imaging prior to surgery.
 

Treatment outcomes for diaphragmatic endometriosis

Reflecting the literature, surgery to remove the endometriosis lesions was mainly laparoscopic with 47% abdominal excisions, and 29% abdominal ablations; 6% received open abdominal procedures, and 18% received open thoracotomy or video-assisted thoracoscopic surgery.

The survey asked about postoperative symptoms 6 months after surgery and at the time of survey. Symptoms at 6 months post surgery had completely resolved in 18%, shown significant improvement in 48%, and no improvement in 20%. Worsening of symptoms was seen in 14%. Long-term pain was reported by 21% as severe, 27% as moderate, 35% as mild, and 17% had no symptoms.

Further findings included that 23% underwent additional procedures to treat their diaphragmatic endometriosis, and that there was no significant difference between excision and ablation, nor between age of onset of symptoms or length of diagnostic delay.

“Surgical treatment to remove these extra pelvic deposits of endometriosis will depend upon the type and distribution of thoracic endometriosis and a variety of surgical specialties may need to be involved including gynecologists, cardiothoracic, and upper gastrointestinal/liver surgeons,” Dr. Clark said.

He added that familiar hormonal medical treatments for more typical pelvic endometriosis should also be considered for primary and maintenance treatment. “These data suggest a high symptomatic recurrence rate after surgical treatment and so medical treatments should be considered to try and minimize the risks of endometriosis symptoms returning.”

Dr. Clark also pointed out that multidisciplinary clinical teams should be established in specialized centers to plan surgical and medical management to enhance clinical outcomes and collect data to better understand this enigmatic condition.

Ms. Piccus and Dr. Clark have no relevant conflicts of interest.

Diaphragmatic endometriosis is often diagnosed several years after the start of symptoms – mainly moderate to severe pain – and this is potentially because of general lack of awareness of diaphragmatic endometriosis among the general population and medical professionals.

Findings of the international survey that explored the diagnosis and treatment of diaphragmatic endometriosis were presented at this year’s Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress by medical student Rachel Piccus, MSc, based at the University of Birmingham (England). Robert Sutcliffe, MD, consultant in hepatobiliary and pancreatic surgery, at Queen Elizabeth Hospital Birmingham was senior author. Results were also published in the May 2021 issue of the European Journal of Obstetrics and Gynaecology and Reproductive Biology.

The study found that it took an average of five visits to a primary physician before referral to a gynecologist.

“Late diagnosis could also be due to the idea that diaphragmatic endometriosis symptoms often present before pelvic symptoms and therefore the site of pain is considered atypical for pelvic endometriosis,” Ms. Piccus said, adding that “clinicians are screening for cyclical pain, which is typical of endometriosis, but our study has shown that pain can in fact be more frequent – daily and weekly.”

These significant diagnostic delays, seen from the time of the initial primary care and gynecology consultation has the potential to significantly affect quality of life as seen in pelvic endometriosis, said Ms. Piccus. “These delays are partly due to a lack of awareness among gynecologists, but could also be due to pelvic laparoscopy being insufficient to examine the diaphragm behind the liver.”

Justin Clark, MD, consultant gynaecologist, Birmingham (England) Women’s and Children Hospital, moderated the session and agreed that the study highlights the need for greater awareness of this variant of endometriosis. “Whilst endometriosis affecting the diaphragm, subdiaphragm, and thorax is rare, the condition causes substantial morbidity.”

“Greater knowledge of thoracic endometriosis amongst clinicians in both primary and secondary care is needed to ensure accurate and timely diagnosis,” he added.

Diaphragmatic endometriosis is estimated to affect 1%-1.5% of all endometriosis patients and presents as cyclical pain in the chest, abdomen, and shoulder tip, as well as other respiratory symptoms such as catamenial pneumothorax and difficulty breathing.

“Cross-sectional imaging has shown low sensitivity so upper abdominal laparoscopy is the gold standard; however, this has implications for diagnostic delay because a strong clinical suspicion is required to refer for this invasive procedure,” explained Ms. Piccus referring to one of the reasons underpinning the need for the study.

When successfully diagnosed, treatment requires excision or ablation surgery and studies show symptomatic relief in 75%-100% of cases.

To gauge the extent of delayed diagnosis as well as treatment outcomes from a patient perspective, Ms. Piccus circulated an anonymous online survey among women with a previous history of surgery for diaphragmatic endometriosis.
 

Diaphragmatic endometriosis pain – daily and weekly as well as cyclical

A total of 137 participants responded to the survey, with a median age of 34 years (range, 19-53). Median age of diaphragmatic endometriosis onset was 27 years (range, 11-50), and importantly, diaphragmatic endometriosis symptoms started before pelvic symptoms in 90 respondents (66%).

The dominant symptom was pain. A total of 38% reported cyclical pain (related to endometrial shedding during menstruation), 15% weekly pain, and 47% daily pain, both of which were worse during the menstrual cycle. Furthermore, 14% reported other symptoms including catamenial pneumothorax, difficulty breathing, and hemoptysis.

“Whilst this cyclical pain is typical of endometriosis, we see that diagnostic delays may be due to misdiagnosis because clinicians are screening for this cyclical pain whilst our study has shown that pain can in fact be more frequent, being daily and weekly,” noted Ms. Piccus. Moderate to severe pain was reported in 67% of respondents and moderate in 31%, only 2% reported pain as mild.

Location of pain comprised moderate to severe pain in the upper abdomen (68%), chest (64%) and shoulder (54%). Pain was right-sided in 54%, left-sided in 11% and bilateral in 35%. Upper back and neck were also reported as sites of pain.

Indirectly providing a measure of the lack of awareness of diaphragmatic endometriosis on behalf of primary care, 122 participants reported initially visiting their primary care physician for help and 65 were given a diagnosis – in only 14 cases was that diaphragmatic endometriosis. There were a range of other gynecologic (e.g. ovarian cyst, two), respiratory (spontaneous pneumothorax, seven), gastrointestinal (gastritis/reflux, eight), musculoskeletal (six), and psychological (anxiety/stress, four) diagnoses.

A median of 5 primary care consultations (range, 1-100) were required before referral to a gynecologist, with 30% seeing a primary care physician over 10 times. A further 14 patients self-referred to gynecologist.

“These findings have implications for diagnostic delay, added Ms. Piccus. “While the majority of respondents were diagnosed less than a year from the first GP visit, the median delay was 2 years, with 31% diagnosed after 5 or more years. One took 23 years for an initial diagnosis.”

Most cases were diagnosed at the time of surgery – 93%, with 52% at pelvic laparoscopy, 35% upper abdominal laparoscopy, with 30% requiring two or more laparoscopies before they were diagnosed with diaphragmatic endometriosis. A total of 7% were diagnosed via cross-sectional imaging prior to surgery.
 

Treatment outcomes for diaphragmatic endometriosis

Reflecting the literature, surgery to remove the endometriosis lesions was mainly laparoscopic with 47% abdominal excisions, and 29% abdominal ablations; 6% received open abdominal procedures, and 18% received open thoracotomy or video-assisted thoracoscopic surgery.

The survey asked about postoperative symptoms 6 months after surgery and at the time of survey. Symptoms at 6 months post surgery had completely resolved in 18%, shown significant improvement in 48%, and no improvement in 20%. Worsening of symptoms was seen in 14%. Long-term pain was reported by 21% as severe, 27% as moderate, 35% as mild, and 17% had no symptoms.

Further findings included that 23% underwent additional procedures to treat their diaphragmatic endometriosis, and that there was no significant difference between excision and ablation, nor between age of onset of symptoms or length of diagnostic delay.

“Surgical treatment to remove these extra pelvic deposits of endometriosis will depend upon the type and distribution of thoracic endometriosis and a variety of surgical specialties may need to be involved including gynecologists, cardiothoracic, and upper gastrointestinal/liver surgeons,” Dr. Clark said.

He added that familiar hormonal medical treatments for more typical pelvic endometriosis should also be considered for primary and maintenance treatment. “These data suggest a high symptomatic recurrence rate after surgical treatment and so medical treatments should be considered to try and minimize the risks of endometriosis symptoms returning.”

Dr. Clark also pointed out that multidisciplinary clinical teams should be established in specialized centers to plan surgical and medical management to enhance clinical outcomes and collect data to better understand this enigmatic condition.

Ms. Piccus and Dr. Clark have no relevant conflicts of interest.

Women who receive pellet hormonal therapy may be significantly more likely to have side effects such as mood swings, anxiety, breast tenderness, hair pattern change, acne, and weight gain, compared with women who receive hormonal treatments that have been approved by the Food and Drug Administration, a study indicates.

In addition, abnormal uterine bleeding may be significantly more common in women who receive pellets than it is in women who receive Food and Drug Administration–approved options, according to the retrospective study, which was published online in Menopause.

Women receiving pellets also were more likely to undergo hysterectomy while on hormonal therapy, and they had higher supraphysiological levels of estradiol and total testosterone during treatment, compared with women on conventional therapy, the study of 539 women shows.

The findings, which had been presented at the North American Menopause Society annual meeting, were highlighted during a lecture at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

The data are “not very reassuring at all,” said Robert P. Kauffman, MD, a professor of obstetrics and gynecology at Texas Tech University, Amarillo, who was not involved in the study.

Dr. Kauffman commented on the research during a review of concerns surrounding non–FDA-approved hormone replacement therapies at the ACOG meeting. Concerns include variations in compounded products, a lack of randomized, controlled trial data supporting their use, and ethical dilemmas that may exist if clinicians have financial incentives to provide compounded bioidentical hormone therapy over FDA-approved treatments.

No peer-reviewed studies show that compounded hormone creams or pellets are safer, more efficacious, or less likely to cause adverse effects, compared with FDA-approved products, Dr. Kauffman said.
 

Data from Pennsylvania

For the retrospective study, Xuezhi (Daniel) Jiang, MD, PhD, and colleagues identified postmenopausal patients in the Reading Hospital Electronic Medical Record System, including 10,801 on FDA-approved hormonal therapy and 1,061 on pellet hormonal therapy. Their analysis focused on data from the medical records of 384 women on pellet hormonal therapy and 155 women on FDA-approved hormonal therapy. Dr. Jiang is affiliated with the department of obstetrics and gynecology at Reading (Pa.) Hospital and Sidney Kimmel Medical College, Philadelphia.

The researchers examined data from 2005 to 2017 for patients in the pellet therapy group, and from 1985 to 2017 for patients in the conventional therapy group.

Patients in the conventional therapy group received 24 brands of FDA-approved hormone products; 4.5% received testosterone or methyltestosterone in addition to estrogen. Patients in the pellet therapy group had pellets prescribed by clinicians at two private practices in the hospital system that use this treatment approach. Patients in the pellet group received compounded estradiol and testosterone pellets made at a pharmacy in Tennessee.* Almost all of the patients in the pellet group received testosterone and estradiol pellets.

Low libido was listed as a reason why women started treatment for 83.5% of the pellet group versus 4.5% of the conventional therapy group.

In all, 57.6% of patients on pellet therapy had side effects, versus 14.8% on FDA-approved therapy, the researchers found. Patients on pellet hormonal therapy reported higher incidence of mood swings (7% vs. 1.9%), anxiety (18.5% vs. 5.8%), breast tenderness (10.1% vs. 2.6%), hair pattern change (13.5% vs. 2.6%), acne (8.6% vs. 1.3%), and weight gain (34.4% vs 4.5%), relative to patients on FDA-approved options.

Among those with an intact uterus when starting therapy (246 of those on pellets and 133 of those on FDA-approved treatments), abnormal uterine bleeding occurred in 55.3% on pellets, compared with 15.2% on FDA-approved treatments (adjusted odds ratio, 7.9). Hysterectomy secondary to abnormal uterine bleeding occurred in 20.3% of the patients on pellets versus 6.3% on FDA-approved treatments (aOR, 3.2).

In many cases, records show that patients chose to have a hysterectomy so they could continue pellet therapy without worrying about abnormal uterine bleeding, Dr. Jiang said in an interview.

Dr. Kauffman has seen patients on pellet therapy, usually implanted by family physicians, develop postmenopausal bleeding because of high levels of estrogen. “Our experience has been too that, if you have pellets, you are more likely to get a hysterectomy for bleeding issues. And I think these are the safety issues that need to be looked at on a broader scope,” he said in an interview.

Although hysterectomy may stop the bleeding, other safety risks may remain with pellet therapy, noted Sharon Winer, MD, MPH, an obstetrician and gynecologist with a subspecialty in reproductive endocrinology and infertility who practices in Beverly Hills, Calif.

Pellets, which are about the size of a grain of rice, typically are implanted in the hip, lower abdomen, or buttock and release hormones over 3-6 months. The pellets are not retrievable. “The question becomes, what if she has a new breast cancer diagnosis or a diagnosis where estrogen is contraindicated? She has got that estrogen already in her system,” Dr. Winer said.

“The hysterectomy may solve the bleeding problem ... but it doesn’t solve the safety problem overall,” said Dr. Winer, who also is a professor of obstetrics and gynecology and codirector of the reproductive endocrinology and infertility clinic at the University of Southern California, Los Angeles.

Elevated levels

Average peak serum estradiol was significantly higher in the pellet treatment group than in the conventional therapy group (237.70 pg/mL vs. 93.45 pg/mL), as was average peak serum testosterone (192.84 ng/dL vs. 15.59 ng/dL), the researchers reported. Patients on FDA-approved treatments were less likely to have had their hormone levels measured. How concentrations of hormone levels correlate with side effects is unclear, Dr. Jiang said.

The study was limited by its single-institution, retrospective design, and some patient characteristics differed between the treatment groups, the authors noted.

Still, “clinicians ought to be mindful of fully counseling patients on side effects identified in the current study,” Dr. Jiang and coauthors concluded. Clinicians also need to discuss potential risks of breast cancer, endometrial cancer, and cardiovascular disease with patients.

Many primary care clinicians rely on outdated information from the Women’s Health Initiative, published in 2002 and 2004, in their understanding of postmenopausal hormonal therapy and its risks and benefits, Dr. Jiang said. And some patients consider custom-compounded hormone therapy to be safer and more natural, “which is totally misleading.”

Pellets and other custom-compounded medicine containing testosterone may make patients feel better and more energetic, Dr. Jiang acknowledged. “That’s a reason why patients ... tend to stay on, even though they have side effects. The only issue is the safety.”

Additional questions remain. The researchers recently started to examine rates of breast cancer and abnormal breast pathology and mammogram results. “It’s a long journey,” he said.

Plenty of approved options

Custom-compounded medicines are not FDA approved and are not recommended by medical menopause societies, Dr. Jiang said. Meanwhile, plenty of approved hormone therapies, including bioidentical treatments, have safety data and are available.

A 2020 consensus study report from the National Academies of Sciences, Engineering, and Medicine that examined the use of compounded hormonal therapy and provides guidance for clinicians is a good start in addressing this major issue, he added.

A committee determined “there is insufficient evidence to support the overall clinical utility of [compounded bioidentical hormone therapies] as treatment for menopause and male hypogonadism symptoms.”

If an FDA-approved option is available, “I would always go with an FDA-approved product before I would go with a compounded product,” Dr. Winer said. A 2012 fungal meningitis outbreak linked to a compounding pharmacy highlighted risks associated with poor quality compounded drugs.

“I think at least now it is recognized that compounding is an issue that has got to be dealt with,” Dr. Winer said. “It is just that it is so widespread and it is sometimes under the radar ... that I think it is really hard for the FDA to get a handle on it.”

Dr. Winer has seen patients on compounded treatments who are underdosed and patients who are overdosed. “I’ve also seen patients who do quite well with it, but I’m not happy continuing it because tomorrow there may be inconsistency in potency or quality resulting in a different clinical response,” she said.

Nevertheless, compounded pharmacies are needed, Dr. Winer said. If she wants to give natural progesterone that is FDA approved but happens to be made with peanut oil, she will have a compounding pharmacy make it with canola oil instead if a patient has a peanut allergy, for example. Other patients need dosages that are so low that they are not available as FDA-approved products.

Dr. Jiang and Dr. Kauffman had no relevant financial disclosures. Dr. Winer has done work with AbbVie (related to endometriosis), TherapeuticsMD (related to a menopause bioidentical hormonal pill and vaginal estrogen product), and Biogix (related to an antioxidant supplement for menopause symptoms).

jremaly@mdedge.com

*This story was updated on 6/22/2021.

Women who receive pellet hormonal therapy may be significantly more likely to have side effects such as mood swings, anxiety, breast tenderness, hair pattern change, acne, and weight gain, compared with women who receive hormonal treatments that have been approved by the Food and Drug Administration, a study indicates.

In addition, abnormal uterine bleeding may be significantly more common in women who receive pellets than it is in women who receive Food and Drug Administration–approved options, according to the retrospective study, which was published online in Menopause.

Women receiving pellets also were more likely to undergo hysterectomy while on hormonal therapy, and they had higher supraphysiological levels of estradiol and total testosterone during treatment, compared with women on conventional therapy, the study of 539 women shows.

The findings, which had been presented at the North American Menopause Society annual meeting, were highlighted during a lecture at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

The data are “not very reassuring at all,” said Robert P. Kauffman, MD, a professor of obstetrics and gynecology at Texas Tech University, Amarillo, who was not involved in the study.

Dr. Kauffman commented on the research during a review of concerns surrounding non–FDA-approved hormone replacement therapies at the ACOG meeting. Concerns include variations in compounded products, a lack of randomized, controlled trial data supporting their use, and ethical dilemmas that may exist if clinicians have financial incentives to provide compounded bioidentical hormone therapy over FDA-approved treatments.

No peer-reviewed studies show that compounded hormone creams or pellets are safer, more efficacious, or less likely to cause adverse effects, compared with FDA-approved products, Dr. Kauffman said.
 

Data from Pennsylvania

For the retrospective study, Xuezhi (Daniel) Jiang, MD, PhD, and colleagues identified postmenopausal patients in the Reading Hospital Electronic Medical Record System, including 10,801 on FDA-approved hormonal therapy and 1,061 on pellet hormonal therapy. Their analysis focused on data from the medical records of 384 women on pellet hormonal therapy and 155 women on FDA-approved hormonal therapy. Dr. Jiang is affiliated with the department of obstetrics and gynecology at Reading (Pa.) Hospital and Sidney Kimmel Medical College, Philadelphia.

The researchers examined data from 2005 to 2017 for patients in the pellet therapy group, and from 1985 to 2017 for patients in the conventional therapy group.

Patients in the conventional therapy group received 24 brands of FDA-approved hormone products; 4.5% received testosterone or methyltestosterone in addition to estrogen. Patients in the pellet therapy group had pellets prescribed by clinicians at two private practices in the hospital system that use this treatment approach. Patients in the pellet group received compounded estradiol and testosterone pellets made at a pharmacy in Tennessee.* Almost all of the patients in the pellet group received testosterone and estradiol pellets.

Low libido was listed as a reason why women started treatment for 83.5% of the pellet group versus 4.5% of the conventional therapy group.

In all, 57.6% of patients on pellet therapy had side effects, versus 14.8% on FDA-approved therapy, the researchers found. Patients on pellet hormonal therapy reported higher incidence of mood swings (7% vs. 1.9%), anxiety (18.5% vs. 5.8%), breast tenderness (10.1% vs. 2.6%), hair pattern change (13.5% vs. 2.6%), acne (8.6% vs. 1.3%), and weight gain (34.4% vs 4.5%), relative to patients on FDA-approved options.

Among those with an intact uterus when starting therapy (246 of those on pellets and 133 of those on FDA-approved treatments), abnormal uterine bleeding occurred in 55.3% on pellets, compared with 15.2% on FDA-approved treatments (adjusted odds ratio, 7.9). Hysterectomy secondary to abnormal uterine bleeding occurred in 20.3% of the patients on pellets versus 6.3% on FDA-approved treatments (aOR, 3.2).

In many cases, records show that patients chose to have a hysterectomy so they could continue pellet therapy without worrying about abnormal uterine bleeding, Dr. Jiang said in an interview.

Dr. Kauffman has seen patients on pellet therapy, usually implanted by family physicians, develop postmenopausal bleeding because of high levels of estrogen. “Our experience has been too that, if you have pellets, you are more likely to get a hysterectomy for bleeding issues. And I think these are the safety issues that need to be looked at on a broader scope,” he said in an interview.

Although hysterectomy may stop the bleeding, other safety risks may remain with pellet therapy, noted Sharon Winer, MD, MPH, an obstetrician and gynecologist with a subspecialty in reproductive endocrinology and infertility who practices in Beverly Hills, Calif.

Pellets, which are about the size of a grain of rice, typically are implanted in the hip, lower abdomen, or buttock and release hormones over 3-6 months. The pellets are not retrievable. “The question becomes, what if she has a new breast cancer diagnosis or a diagnosis where estrogen is contraindicated? She has got that estrogen already in her system,” Dr. Winer said.

“The hysterectomy may solve the bleeding problem ... but it doesn’t solve the safety problem overall,” said Dr. Winer, who also is a professor of obstetrics and gynecology and codirector of the reproductive endocrinology and infertility clinic at the University of Southern California, Los Angeles.

Elevated levels

Average peak serum estradiol was significantly higher in the pellet treatment group than in the conventional therapy group (237.70 pg/mL vs. 93.45 pg/mL), as was average peak serum testosterone (192.84 ng/dL vs. 15.59 ng/dL), the researchers reported. Patients on FDA-approved treatments were less likely to have had their hormone levels measured. How concentrations of hormone levels correlate with side effects is unclear, Dr. Jiang said.

The study was limited by its single-institution, retrospective design, and some patient characteristics differed between the treatment groups, the authors noted.

Still, “clinicians ought to be mindful of fully counseling patients on side effects identified in the current study,” Dr. Jiang and coauthors concluded. Clinicians also need to discuss potential risks of breast cancer, endometrial cancer, and cardiovascular disease with patients.

Many primary care clinicians rely on outdated information from the Women’s Health Initiative, published in 2002 and 2004, in their understanding of postmenopausal hormonal therapy and its risks and benefits, Dr. Jiang said. And some patients consider custom-compounded hormone therapy to be safer and more natural, “which is totally misleading.”

Pellets and other custom-compounded medicine containing testosterone may make patients feel better and more energetic, Dr. Jiang acknowledged. “That’s a reason why patients ... tend to stay on, even though they have side effects. The only issue is the safety.”

Additional questions remain. The researchers recently started to examine rates of breast cancer and abnormal breast pathology and mammogram results. “It’s a long journey,” he said.

Plenty of approved options

Custom-compounded medicines are not FDA approved and are not recommended by medical menopause societies, Dr. Jiang said. Meanwhile, plenty of approved hormone therapies, including bioidentical treatments, have safety data and are available.

A 2020 consensus study report from the National Academies of Sciences, Engineering, and Medicine that examined the use of compounded hormonal therapy and provides guidance for clinicians is a good start in addressing this major issue, he added.

A committee determined “there is insufficient evidence to support the overall clinical utility of [compounded bioidentical hormone therapies] as treatment for menopause and male hypogonadism symptoms.”

If an FDA-approved option is available, “I would always go with an FDA-approved product before I would go with a compounded product,” Dr. Winer said. A 2012 fungal meningitis outbreak linked to a compounding pharmacy highlighted risks associated with poor quality compounded drugs.

“I think at least now it is recognized that compounding is an issue that has got to be dealt with,” Dr. Winer said. “It is just that it is so widespread and it is sometimes under the radar ... that I think it is really hard for the FDA to get a handle on it.”

Dr. Winer has seen patients on compounded treatments who are underdosed and patients who are overdosed. “I’ve also seen patients who do quite well with it, but I’m not happy continuing it because tomorrow there may be inconsistency in potency or quality resulting in a different clinical response,” she said.

Nevertheless, compounded pharmacies are needed, Dr. Winer said. If she wants to give natural progesterone that is FDA approved but happens to be made with peanut oil, she will have a compounding pharmacy make it with canola oil instead if a patient has a peanut allergy, for example. Other patients need dosages that are so low that they are not available as FDA-approved products.

Dr. Jiang and Dr. Kauffman had no relevant financial disclosures. Dr. Winer has done work with AbbVie (related to endometriosis), TherapeuticsMD (related to a menopause bioidentical hormonal pill and vaginal estrogen product), and Biogix (related to an antioxidant supplement for menopause symptoms).

jremaly@mdedge.com

*This story was updated on 6/22/2021.

Women who receive pellet hormonal therapy may be significantly more likely to have side effects such as mood swings, anxiety, breast tenderness, hair pattern change, acne, and weight gain, compared with women who receive hormonal treatments that have been approved by the Food and Drug Administration, a study indicates.

In addition, abnormal uterine bleeding may be significantly more common in women who receive pellets than it is in women who receive Food and Drug Administration–approved options, according to the retrospective study, which was published online in Menopause.

Women receiving pellets also were more likely to undergo hysterectomy while on hormonal therapy, and they had higher supraphysiological levels of estradiol and total testosterone during treatment, compared with women on conventional therapy, the study of 539 women shows.

The findings, which had been presented at the North American Menopause Society annual meeting, were highlighted during a lecture at the 2021 virtual meeting of the American College of Obstetricians and Gynecologists.

The data are “not very reassuring at all,” said Robert P. Kauffman, MD, a professor of obstetrics and gynecology at Texas Tech University, Amarillo, who was not involved in the study.

Dr. Kauffman commented on the research during a review of concerns surrounding non–FDA-approved hormone replacement therapies at the ACOG meeting. Concerns include variations in compounded products, a lack of randomized, controlled trial data supporting their use, and ethical dilemmas that may exist if clinicians have financial incentives to provide compounded bioidentical hormone therapy over FDA-approved treatments.

No peer-reviewed studies show that compounded hormone creams or pellets are safer, more efficacious, or less likely to cause adverse effects, compared with FDA-approved products, Dr. Kauffman said.
 

Data from Pennsylvania

For the retrospective study, Xuezhi (Daniel) Jiang, MD, PhD, and colleagues identified postmenopausal patients in the Reading Hospital Electronic Medical Record System, including 10,801 on FDA-approved hormonal therapy and 1,061 on pellet hormonal therapy. Their analysis focused on data from the medical records of 384 women on pellet hormonal therapy and 155 women on FDA-approved hormonal therapy. Dr. Jiang is affiliated with the department of obstetrics and gynecology at Reading (Pa.) Hospital and Sidney Kimmel Medical College, Philadelphia.

The researchers examined data from 2005 to 2017 for patients in the pellet therapy group, and from 1985 to 2017 for patients in the conventional therapy group.

Patients in the conventional therapy group received 24 brands of FDA-approved hormone products; 4.5% received testosterone or methyltestosterone in addition to estrogen. Patients in the pellet therapy group had pellets prescribed by clinicians at two private practices in the hospital system that use this treatment approach. Patients in the pellet group received compounded estradiol and testosterone pellets made at a pharmacy in Tennessee.* Almost all of the patients in the pellet group received testosterone and estradiol pellets.

Low libido was listed as a reason why women started treatment for 83.5% of the pellet group versus 4.5% of the conventional therapy group.

In all, 57.6% of patients on pellet therapy had side effects, versus 14.8% on FDA-approved therapy, the researchers found. Patients on pellet hormonal therapy reported higher incidence of mood swings (7% vs. 1.9%), anxiety (18.5% vs. 5.8%), breast tenderness (10.1% vs. 2.6%), hair pattern change (13.5% vs. 2.6%), acne (8.6% vs. 1.3%), and weight gain (34.4% vs 4.5%), relative to patients on FDA-approved options.

Among those with an intact uterus when starting therapy (246 of those on pellets and 133 of those on FDA-approved treatments), abnormal uterine bleeding occurred in 55.3% on pellets, compared with 15.2% on FDA-approved treatments (adjusted odds ratio, 7.9). Hysterectomy secondary to abnormal uterine bleeding occurred in 20.3% of the patients on pellets versus 6.3% on FDA-approved treatments (aOR, 3.2).

In many cases, records show that patients chose to have a hysterectomy so they could continue pellet therapy without worrying about abnormal uterine bleeding, Dr. Jiang said in an interview.

Dr. Kauffman has seen patients on pellet therapy, usually implanted by family physicians, develop postmenopausal bleeding because of high levels of estrogen. “Our experience has been too that, if you have pellets, you are more likely to get a hysterectomy for bleeding issues. And I think these are the safety issues that need to be looked at on a broader scope,” he said in an interview.

Although hysterectomy may stop the bleeding, other safety risks may remain with pellet therapy, noted Sharon Winer, MD, MPH, an obstetrician and gynecologist with a subspecialty in reproductive endocrinology and infertility who practices in Beverly Hills, Calif.

Pellets, which are about the size of a grain of rice, typically are implanted in the hip, lower abdomen, or buttock and release hormones over 3-6 months. The pellets are not retrievable. “The question becomes, what if she has a new breast cancer diagnosis or a diagnosis where estrogen is contraindicated? She has got that estrogen already in her system,” Dr. Winer said.

“The hysterectomy may solve the bleeding problem ... but it doesn’t solve the safety problem overall,” said Dr. Winer, who also is a professor of obstetrics and gynecology and codirector of the reproductive endocrinology and infertility clinic at the University of Southern California, Los Angeles.

Elevated levels

Average peak serum estradiol was significantly higher in the pellet treatment group than in the conventional therapy group (237.70 pg/mL vs. 93.45 pg/mL), as was average peak serum testosterone (192.84 ng/dL vs. 15.59 ng/dL), the researchers reported. Patients on FDA-approved treatments were less likely to have had their hormone levels measured. How concentrations of hormone levels correlate with side effects is unclear, Dr. Jiang said.

The study was limited by its single-institution, retrospective design, and some patient characteristics differed between the treatment groups, the authors noted.

Still, “clinicians ought to be mindful of fully counseling patients on side effects identified in the current study,” Dr. Jiang and coauthors concluded. Clinicians also need to discuss potential risks of breast cancer, endometrial cancer, and cardiovascular disease with patients.

Many primary care clinicians rely on outdated information from the Women’s Health Initiative, published in 2002 and 2004, in their understanding of postmenopausal hormonal therapy and its risks and benefits, Dr. Jiang said. And some patients consider custom-compounded hormone therapy to be safer and more natural, “which is totally misleading.”

Pellets and other custom-compounded medicine containing testosterone may make patients feel better and more energetic, Dr. Jiang acknowledged. “That’s a reason why patients ... tend to stay on, even though they have side effects. The only issue is the safety.”

Additional questions remain. The researchers recently started to examine rates of breast cancer and abnormal breast pathology and mammogram results. “It’s a long journey,” he said.

Plenty of approved options

Custom-compounded medicines are not FDA approved and are not recommended by medical menopause societies, Dr. Jiang said. Meanwhile, plenty of approved hormone therapies, including bioidentical treatments, have safety data and are available.

A 2020 consensus study report from the National Academies of Sciences, Engineering, and Medicine that examined the use of compounded hormonal therapy and provides guidance for clinicians is a good start in addressing this major issue, he added.

A committee determined “there is insufficient evidence to support the overall clinical utility of [compounded bioidentical hormone therapies] as treatment for menopause and male hypogonadism symptoms.”

If an FDA-approved option is available, “I would always go with an FDA-approved product before I would go with a compounded product,” Dr. Winer said. A 2012 fungal meningitis outbreak linked to a compounding pharmacy highlighted risks associated with poor quality compounded drugs.

“I think at least now it is recognized that compounding is an issue that has got to be dealt with,” Dr. Winer said. “It is just that it is so widespread and it is sometimes under the radar ... that I think it is really hard for the FDA to get a handle on it.”

Dr. Winer has seen patients on compounded treatments who are underdosed and patients who are overdosed. “I’ve also seen patients who do quite well with it, but I’m not happy continuing it because tomorrow there may be inconsistency in potency or quality resulting in a different clinical response,” she said.

Nevertheless, compounded pharmacies are needed, Dr. Winer said. If she wants to give natural progesterone that is FDA approved but happens to be made with peanut oil, she will have a compounding pharmacy make it with canola oil instead if a patient has a peanut allergy, for example. Other patients need dosages that are so low that they are not available as FDA-approved products.

Dr. Jiang and Dr. Kauffman had no relevant financial disclosures. Dr. Winer has done work with AbbVie (related to endometriosis), TherapeuticsMD (related to a menopause bioidentical hormonal pill and vaginal estrogen product), and Biogix (related to an antioxidant supplement for menopause symptoms).

jremaly@mdedge.com

*This story was updated on 6/22/2021.

Black women exposed to ozone air pollution have an increased risk of developing fibroids, according to new research published in Human Production.

Uterine fibroids are a common type of pelvic growth, affecting up to 80% of women by the time they reach age 50, according to the U.S. Department of Health and Human Services. Black women are hit hardest by fibroids; they are diagnosed two to three times the rate of White women and tend to have more severe symptoms.

Researchers are unclear on why exposure to ozone air pollution increases the risk of developing fibroids. However, they believe that when it comes to identifying causes of fibroids and explanations for racial disparities in fibroids, more research that focuses on environmental and neighborhood-level risk factors could help inform policy and interventions to improve gynecologic health.

“A large body of literature from the environmental justice field has documented that people of color, and Black people specifically, are inequitably exposed to air pollution,” study author Amelia K. Wesselink, PhD, assistant professor at Boston University School of Public Health, said in an interview. “And there is growing evidence that air pollution can influence gynecologic health and therefore may contribute to racial disparities in gynecologic outcomes.”

Dr. Wesselink and colleagues wanted to know the extent to which three air pollutants – particulate matter (PM2.5), nitrogen dioxide (NO₂) and ozone (0₃) – were linked to the development of fibroids. To figure this out, they analyzed data on nearly 22,000 premenopausal Black women who lived in 56 metropolitan areas in the United States between 2007 and 2011. They assigned air pollution exposures to participants’ residential addresses collected at baseline and over follow-up and tried to capture long-term exposure to air pollutants.

During the study, nearly 30% of participants reported that they were diagnosed with fibroids. Researchers observed that the exposure to PM2.5 and NO₂ was not associated with an increased risk of developing these fibroids.

Dr. Wesselink said the findings may have underestimated fibroid incidence, so they “need to be replicated in a prospective, ultrasound-based study that can identify all fibroid cases.”

“There has not been a lot of research on how air pollution influences fibroid risk, but the two studies that are out there show some evidence of an association,” said Dr. Wesselink. “The fact that our results were consistent with this is interesting. The surprising part of our findings was that we observed an association for ozone, but not for PM2.5 or NO₂.”

Nathaniel DeNicola, MD, MSHP, FACOG, a Washington-based obstetrics and gynecology physician affiliated with John Hopkins Health System, applauded the methodology of the study and said the findings prove that patients and doctors should be talking about the environment and exposures to air pollutants.

“[Air pollution] has numerous components to it. And we should try to figure out exactly what components are most dangerous to human health and what doses and what times of life,” said Dr. DeNicola, an environmental health expert.

The increased risk of developing fibroids is a “historical observation” and air pollution may be part of a multifactorial cause of that, Dr. DeNicola said. He said he wouldn’t be surprised if future studies show that “higher exposure [to air pollution] – due to how city planning works, often communities of color are in the areas with the most dense air pollution – exacerbates some other mechanism already in place.

Although it’s unclear how ozone exposure increases fibroid risk, Dr. Wesselink said it may be through a mechanism that is unique to ozone.

“In other words, it might be that there is a factor related to ozone that we did not account for that explains our findings. Vitamin D is a factor that we were not able to account for in this study,” Dr. Wesselink said. “Future work on this topic should consider the role of vitamin D [exposure or deficiency].”

Dr. DeNicola said ozone’s impact may also be tied to its “known association” with hypertension. A 2017 study by Drew B. Day, PhD, of Duke University, Durham, N.C., and colleagues, found that ozone exposure has been linked to hypertension. Meanwhile, a 2015 study has found an association between hypertension and fibroids.

“[This study] does raise an important message. It shines a light where more research needs to be done,” Dr. DeNicola said. “The ozone connection to hypertension was probably most compelling as a true risk factor for uterine fibroids.”

Dr. Wesselink said future work on fibroid etiology should focus on environmental and neighborhood-level exposures to pollutants.

Black women exposed to ozone air pollution have an increased risk of developing fibroids, according to new research published in Human Production.

Uterine fibroids are a common type of pelvic growth, affecting up to 80% of women by the time they reach age 50, according to the U.S. Department of Health and Human Services. Black women are hit hardest by fibroids; they are diagnosed two to three times the rate of White women and tend to have more severe symptoms.

Researchers are unclear on why exposure to ozone air pollution increases the risk of developing fibroids. However, they believe that when it comes to identifying causes of fibroids and explanations for racial disparities in fibroids, more research that focuses on environmental and neighborhood-level risk factors could help inform policy and interventions to improve gynecologic health.

“A large body of literature from the environmental justice field has documented that people of color, and Black people specifically, are inequitably exposed to air pollution,” study author Amelia K. Wesselink, PhD, assistant professor at Boston University School of Public Health, said in an interview. “And there is growing evidence that air pollution can influence gynecologic health and therefore may contribute to racial disparities in gynecologic outcomes.”

Dr. Wesselink and colleagues wanted to know the extent to which three air pollutants – particulate matter (PM2.5), nitrogen dioxide (NO₂) and ozone (0₃) – were linked to the development of fibroids. To figure this out, they analyzed data on nearly 22,000 premenopausal Black women who lived in 56 metropolitan areas in the United States between 2007 and 2011. They assigned air pollution exposures to participants’ residential addresses collected at baseline and over follow-up and tried to capture long-term exposure to air pollutants.

During the study, nearly 30% of participants reported that they were diagnosed with fibroids. Researchers observed that the exposure to PM2.5 and NO₂ was not associated with an increased risk of developing these fibroids.

Dr. Wesselink said the findings may have underestimated fibroid incidence, so they “need to be replicated in a prospective, ultrasound-based study that can identify all fibroid cases.”

“There has not been a lot of research on how air pollution influences fibroid risk, but the two studies that are out there show some evidence of an association,” said Dr. Wesselink. “The fact that our results were consistent with this is interesting. The surprising part of our findings was that we observed an association for ozone, but not for PM2.5 or NO₂.”

Nathaniel DeNicola, MD, MSHP, FACOG, a Washington-based obstetrics and gynecology physician affiliated with John Hopkins Health System, applauded the methodology of the study and said the findings prove that patients and doctors should be talking about the environment and exposures to air pollutants.

“[Air pollution] has numerous components to it. And we should try to figure out exactly what components are most dangerous to human health and what doses and what times of life,” said Dr. DeNicola, an environmental health expert.

The increased risk of developing fibroids is a “historical observation” and air pollution may be part of a multifactorial cause of that, Dr. DeNicola said. He said he wouldn’t be surprised if future studies show that “higher exposure [to air pollution] – due to how city planning works, often communities of color are in the areas with the most dense air pollution – exacerbates some other mechanism already in place.

Although it’s unclear how ozone exposure increases fibroid risk, Dr. Wesselink said it may be through a mechanism that is unique to ozone.

“In other words, it might be that there is a factor related to ozone that we did not account for that explains our findings. Vitamin D is a factor that we were not able to account for in this study,” Dr. Wesselink said. “Future work on this topic should consider the role of vitamin D [exposure or deficiency].”

Dr. DeNicola said ozone’s impact may also be tied to its “known association” with hypertension. A 2017 study by Drew B. Day, PhD, of Duke University, Durham, N.C., and colleagues, found that ozone exposure has been linked to hypertension. Meanwhile, a 2015 study has found an association between hypertension and fibroids.

“[This study] does raise an important message. It shines a light where more research needs to be done,” Dr. DeNicola said. “The ozone connection to hypertension was probably most compelling as a true risk factor for uterine fibroids.”

Dr. Wesselink said future work on fibroid etiology should focus on environmental and neighborhood-level exposures to pollutants.

Black women exposed to ozone air pollution have an increased risk of developing fibroids, according to new research published in Human Production.

Uterine fibroids are a common type of pelvic growth, affecting up to 80% of women by the time they reach age 50, according to the U.S. Department of Health and Human Services. Black women are hit hardest by fibroids; they are diagnosed two to three times the rate of White women and tend to have more severe symptoms.

Researchers are unclear on why exposure to ozone air pollution increases the risk of developing fibroids. However, they believe that when it comes to identifying causes of fibroids and explanations for racial disparities in fibroids, more research that focuses on environmental and neighborhood-level risk factors could help inform policy and interventions to improve gynecologic health.

“A large body of literature from the environmental justice field has documented that people of color, and Black people specifically, are inequitably exposed to air pollution,” study author Amelia K. Wesselink, PhD, assistant professor at Boston University School of Public Health, said in an interview. “And there is growing evidence that air pollution can influence gynecologic health and therefore may contribute to racial disparities in gynecologic outcomes.”

Dr. Wesselink and colleagues wanted to know the extent to which three air pollutants – particulate matter (PM2.5), nitrogen dioxide (NO₂) and ozone (0₃) – were linked to the development of fibroids. To figure this out, they analyzed data on nearly 22,000 premenopausal Black women who lived in 56 metropolitan areas in the United States between 2007 and 2011. They assigned air pollution exposures to participants’ residential addresses collected at baseline and over follow-up and tried to capture long-term exposure to air pollutants.

During the study, nearly 30% of participants reported that they were diagnosed with fibroids. Researchers observed that the exposure to PM2.5 and NO₂ was not associated with an increased risk of developing these fibroids.

Dr. Wesselink said the findings may have underestimated fibroid incidence, so they “need to be replicated in a prospective, ultrasound-based study that can identify all fibroid cases.”

“There has not been a lot of research on how air pollution influences fibroid risk, but the two studies that are out there show some evidence of an association,” said Dr. Wesselink. “The fact that our results were consistent with this is interesting. The surprising part of our findings was that we observed an association for ozone, but not for PM2.5 or NO₂.”

Nathaniel DeNicola, MD, MSHP, FACOG, a Washington-based obstetrics and gynecology physician affiliated with John Hopkins Health System, applauded the methodology of the study and said the findings prove that patients and doctors should be talking about the environment and exposures to air pollutants.

“[Air pollution] has numerous components to it. And we should try to figure out exactly what components are most dangerous to human health and what doses and what times of life,” said Dr. DeNicola, an environmental health expert.

The increased risk of developing fibroids is a “historical observation” and air pollution may be part of a multifactorial cause of that, Dr. DeNicola said. He said he wouldn’t be surprised if future studies show that “higher exposure [to air pollution] – due to how city planning works, often communities of color are in the areas with the most dense air pollution – exacerbates some other mechanism already in place.

Although it’s unclear how ozone exposure increases fibroid risk, Dr. Wesselink said it may be through a mechanism that is unique to ozone.

“In other words, it might be that there is a factor related to ozone that we did not account for that explains our findings. Vitamin D is a factor that we were not able to account for in this study,” Dr. Wesselink said. “Future work on this topic should consider the role of vitamin D [exposure or deficiency].”

Dr. DeNicola said ozone’s impact may also be tied to its “known association” with hypertension. A 2017 study by Drew B. Day, PhD, of Duke University, Durham, N.C., and colleagues, found that ozone exposure has been linked to hypertension. Meanwhile, a 2015 study has found an association between hypertension and fibroids.

“[This study] does raise an important message. It shines a light where more research needs to be done,” Dr. DeNicola said. “The ozone connection to hypertension was probably most compelling as a true risk factor for uterine fibroids.”

Dr. Wesselink said future work on fibroid etiology should focus on environmental and neighborhood-level exposures to pollutants.

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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

Women with osteoporosis, low bone density, or a previous vertebral fracture show significant increases in the risk of hearing loss compared to those without osteoporosis, according to a new study with more than 3 decades of follow-up.

The use of bisphosphonate therapy did not alter the risk, the researchers found.

“To the best of our knowledge, this is the first large longitudinal study to evaluate the relations of bone density, bisphosphonate use, fractures, and risk of hearing loss,” reported Sharon Curhan, MD, and colleagues in research published online in the Journal of the American Geriatric Society.

“In this large nationwide longitudinal study of nearly 144,000 women with up to 34 years of follow-up, we found that osteoporosis or low bone density was independently associated with higher risk of incident moderate or worse hearing loss,” the authors wrote.

“The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates,” they added.
 

Participants were from the nurses’ health study and NHS II

With recent research suggesting a potential link between bisphosphonate use and prevention of noise-induced hearing loss in mice, Dr. Curhan, of the Channing Division of Network Medicine at Brigham and Women’s Hospital, Boston, and colleagues turned to the large longitudinal cohorts of the Nurses’ Health Study (NHS), conducted from 1982 to 2016, and the Nurses’ Health Study II (NHS II), from 1995 to 2017.

In total, the primary analysis included 60,821 women in the NHS and 83,078 in the NHS II.

Women in the NHS were aged 36-61 years at baseline and 70-95 years at the end of follow-up, while in the NHS II, women were aged 31-48 years at baseline and 53-70 years at the end of follow-up.

After multivariate adjustment for key factors including age, race/ethnicity, oral hormone use, and a variety of other factors, women in the NHS with osteoporosis had an increased risk of moderate or worse hearing loss, as self-reported every 2 years, compared to those without osteoporosis (relative risk, 1.14; 95% confidence interval, 1.09-1.19).

And in the NHS II, which also included data on low bone density, the risk of self-reported hearing loss was higher among those with osteoporosis or low bone density (RR, 1.30; 95% CI, 1.21-1.40).

No significant differences were observed in hearing loss risk based on whether women were treated with bisphosphonates, with the mean duration of use of the medication being 5.8 years in the NHS and 3.4 years in the NHS II.

Those who sustained a vertebral fracture also had a higher risk of hearing loss in both studies (NHS: RR, 1.31; NHS II: RR, 1.39).

However, the increased risk of hearing loss was not observed with hip fracture.

“Our findings of up to a 40% higher risk among women with vertebral fracture, but not hip fracture, were intriguing and merit further study,” the authors noted.

“The discordant findings between these skeletal sites may reflect differences in composition and metabolism of bones in the spine and hip and could provide insight into the pathophysiological changes in the ear that may lead to hearing loss,” they added.
 

Audiometric subanalysis

In an analysis of a subcohort of 3,749 women looking at audiometric thresholds for a more precise measure of hearing loss, women with osteoporosis or low bone density continued to show significantly worse hearing loss when treated with bisphosphonates compared to those without osteoporosis or low bone density.

However, there were no significant hearing loss differences among those with osteoporosis who did not take bisphosphonates versus those without osteoporosis.

The authors speculate that the use of bisphosphonates could have been indicative of more severe osteoporosis, hence the poorer audiometric thresholds.

In an interview, Dr. Curhan said the details of bisphosphonate use, such as type and duration, and their role in hearing loss should be further evaluated.

“Possibly, a potential influence of bisphosphonates on the relation of osteoporosis and hearing loss in humans may depend on the type, dose, and timing of bisphosphonate administration,” she observed. “This is an important question for further study.”
 

Mechanisms: Bone loss may extend to ear structures

In terms of the mechanisms linking osteoporosis itself to hearing loss, the authors noted that bone loss, in addition to compromising more prominent skeletal sites, could logically extend to bone-related structures in the ear.

“Bone mass at peripheral sites is correlated with bone mass at central sites, such as hip and spine, with correlation coefficients between 0.6 and 0.7,” they explained. “Plausibly, systemic bone demineralization could involve the temporal bone, the otic capsule, and the middle ear ossicles.”

They noted that hearing loss has been linked to other pathologic bone disorders, including otosclerosis and Paget disease.

Furthermore, imbalances in bone formation and resorption in osteoporosis may lead to alterations in ionic metabolism, which can lead to hearing loss.

Looking ahead, Dr. Curhan and colleagues plan to further examine whether calcium and vitamin D, which are associated with the prevention of osteoporosis, have a role in preventing hearing loss.

In the meantime, the findings underscore that clinicians treating patients with osteoporosis should routinely check patients’ hearing, Dr. Curhan said.

“Undetected and untreated hearing loss can adversely impact social interactions, physical and mental well-being, and daily life,” she said.

“Early detection of hearing loss offers greater opportunity for successful management and to learn strategies for rehabilitation and prevention of further progression.”

The study received support from the National Institutes of Health.
 

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