Women's Health

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

In the United States, breast cancer mortality rates dropped every year for women across all age groups between 1989 and 2010, but after that, the trend stalled for those younger than 40 years.

“It’s clear that mortality rates in women under 40 are no longer decreasing,” lead author R. Edward Hendrick, PhD, clinical professor from the department of radiology at the University of Colorado at Denver, Aurora, stated in a press release. “I estimate that, in 2-3 years, the mortality rate will be increasing significantly in these women.”

These findings were published online Feb. 9, 2021, in Radiology.

The authors speculate that the findings may be related to recommendations for mammography screening.

For their study, the authors analyzed National Center for Health Statistics data for 1969-2017 and delay-adjusted invasive breast cancer incidence rates from the Surveillance, Epidemiology, and End Results program.

They found that breast cancer mortality rates decreased significantly by 1.5%-3.4% per year for all age groups from 1989 to 2010, and by 1.2%-2.2% per year after 2010 for those aged 40-79 years. However, the rates increased after 2010 by a nonsignificant 2.8% per year for women aged 20-29 years and 0.3% per year for those aged 30-39 years.

Distant-stage breast cancer incidence rates increased by more than 4% per year after the year 2000 in women aged 20-39 years.

“Our hope is that these findings focus more attention and research on breast cancer in younger women and what is behind this rapid increase in late-stage cancers,” Dr. Hendrick stated in the press release.

He and his colleagues speculate that the contrast between the upward trend in women aged younger than 40 years and the downward trend in older women highlights the value of mammography and may reflect the benefits of regular screening, which is not currently recommended for women younger than 40 who are not at high risk for breast cancer.

However, other groups, including the American College of Radiology and the Society for Breast Imaging, support starting annual mammograms at age 40 years.

An expert who was approached for comment noted that the incidence of breast cancer increases with age.

It is more common in women as they age, so screening recommendations do not include women aged younger than 40 years unless they are at very high risk for breast cancer, noted Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles.

“The majority of deaths due to breast cancer are in women over age 40. The breast cancer mortality rates per 100,000 as shown [in this study] are about 3 patients/100,000 for the under 40 age group, about 30/100,000 in the 40-69 age group, and about 80/100,000 in the 70 and above age group,” she pointed out.

Dr. Elmore was a coauthor of an editorial regarding the 2019 evidence-based guidance statement from the American College of Physicians . That guidance, which was endorsed by the U.S. Preventive Services Task Force, recommended screening every other year for average-risk women aged 50-74 years, as reported by this news organization.

In their editorial, Dr. Elmore and coauthor Christoph Lee, MD, of the University of Washington, Seattle, applauded the ACP’s approach but stressed that the guidance is not a perfect product and does not “clearly illuminate the full path ahead for every woman.”

Breast cancer screening guidelines continue to evolve, they said, concluding that “physicians are left to use their best judgment based on available research and expert recommendations.”

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

Surgeons have a new tool for use in benign hysterectomies with the Food & Drug Administration’s authorization for marketing of the Hominis Surgical System, a robotic-assisted surgical device. The marketing authorization was granted to Memic Innovative Surgery.

The FDA reviewed the device through the De Novo classification review process, a regulatory pathway for low- to moderate-risk devices of a new type.

The robotically assisted surgical device (RASD) is designed to facilitate transvaginal hysterectomy procedures and salpingo-oophorectomy procedures in patients without cancer.

RASDs are not robots and require human control, but they allow a surgeon to use computer technology to control and move surgical instruments inserted through incisions or orifices. “RASD technology facilitates performing minimally invasive surgery and complex tasks in confined areas inside the body,” according to an FDA press release announcing the authorization.

“The FDA continues to support advancements in safe and effective medical devices that can improve patient experiences when undergoing surgical procedures,” Binita Ashar, MD, of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in the press release. The device represents another minimally invasive option for noncancerous conditions requiring gynecologic surgery.

The FDA also is establishing controls to ensure safety and effectiveness for RASDs, including labeling and performance testing requirements. “When met, the special controls, along with general controls, provide reasonable assurance of safety and effectiveness for devices of this type,” according to the press release.

The Hominis Surgical System involves the use of minimally invasive surgical instruments inserted through the vagina. A video camera is inserted laparoscopically through an abdominal incision; the camera allows the surgeon to visualize the instruments inside the patient.

“The FDA will require the manufacturer to develop and provide a comprehensive training program for surgeons and operating room staff to complete before operation of the device,” according to the press release.

The FDA reviewed data from a clinical study of 30 patients aged 37-79 years who underwent transvaginal total hysterectomy with salpingo-oophorectomy or salpingectomy for benign conditions.

Observed adverse events included minor blood loss, urinary tract infection and delayed healing of the closure made at the top of the vagina (vaginal cuff) that is done as part of a hysterectomy, according to the FDA. However, all 30 procedures were completed with no need for conversion to an open or other procedure.

Surgeons have a new tool for use in benign hysterectomies with the Food & Drug Administration’s authorization for marketing of the Hominis Surgical System, a robotic-assisted surgical device. The marketing authorization was granted to Memic Innovative Surgery.

The FDA reviewed the device through the De Novo classification review process, a regulatory pathway for low- to moderate-risk devices of a new type.

The robotically assisted surgical device (RASD) is designed to facilitate transvaginal hysterectomy procedures and salpingo-oophorectomy procedures in patients without cancer.

RASDs are not robots and require human control, but they allow a surgeon to use computer technology to control and move surgical instruments inserted through incisions or orifices. “RASD technology facilitates performing minimally invasive surgery and complex tasks in confined areas inside the body,” according to an FDA press release announcing the authorization.

“The FDA continues to support advancements in safe and effective medical devices that can improve patient experiences when undergoing surgical procedures,” Binita Ashar, MD, of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in the press release. The device represents another minimally invasive option for noncancerous conditions requiring gynecologic surgery.

The FDA also is establishing controls to ensure safety and effectiveness for RASDs, including labeling and performance testing requirements. “When met, the special controls, along with general controls, provide reasonable assurance of safety and effectiveness for devices of this type,” according to the press release.

The Hominis Surgical System involves the use of minimally invasive surgical instruments inserted through the vagina. A video camera is inserted laparoscopically through an abdominal incision; the camera allows the surgeon to visualize the instruments inside the patient.

“The FDA will require the manufacturer to develop and provide a comprehensive training program for surgeons and operating room staff to complete before operation of the device,” according to the press release.

The FDA reviewed data from a clinical study of 30 patients aged 37-79 years who underwent transvaginal total hysterectomy with salpingo-oophorectomy or salpingectomy for benign conditions.

Observed adverse events included minor blood loss, urinary tract infection and delayed healing of the closure made at the top of the vagina (vaginal cuff) that is done as part of a hysterectomy, according to the FDA. However, all 30 procedures were completed with no need for conversion to an open or other procedure.

Surgeons have a new tool for use in benign hysterectomies with the Food & Drug Administration’s authorization for marketing of the Hominis Surgical System, a robotic-assisted surgical device. The marketing authorization was granted to Memic Innovative Surgery.

The FDA reviewed the device through the De Novo classification review process, a regulatory pathway for low- to moderate-risk devices of a new type.

The robotically assisted surgical device (RASD) is designed to facilitate transvaginal hysterectomy procedures and salpingo-oophorectomy procedures in patients without cancer.

RASDs are not robots and require human control, but they allow a surgeon to use computer technology to control and move surgical instruments inserted through incisions or orifices. “RASD technology facilitates performing minimally invasive surgery and complex tasks in confined areas inside the body,” according to an FDA press release announcing the authorization.

“The FDA continues to support advancements in safe and effective medical devices that can improve patient experiences when undergoing surgical procedures,” Binita Ashar, MD, of the Office of Surgical and Infection Control Devices in the FDA’s Center for Devices and Radiological Health, said in the press release. The device represents another minimally invasive option for noncancerous conditions requiring gynecologic surgery.

The FDA also is establishing controls to ensure safety and effectiveness for RASDs, including labeling and performance testing requirements. “When met, the special controls, along with general controls, provide reasonable assurance of safety and effectiveness for devices of this type,” according to the press release.

The Hominis Surgical System involves the use of minimally invasive surgical instruments inserted through the vagina. A video camera is inserted laparoscopically through an abdominal incision; the camera allows the surgeon to visualize the instruments inside the patient.

“The FDA will require the manufacturer to develop and provide a comprehensive training program for surgeons and operating room staff to complete before operation of the device,” according to the press release.

The FDA reviewed data from a clinical study of 30 patients aged 37-79 years who underwent transvaginal total hysterectomy with salpingo-oophorectomy or salpingectomy for benign conditions.

Observed adverse events included minor blood loss, urinary tract infection and delayed healing of the closure made at the top of the vagina (vaginal cuff) that is done as part of a hysterectomy, according to the FDA. However, all 30 procedures were completed with no need for conversion to an open or other procedure.

Late one night in early February, Jen Gunter, MD, was scrolling online when she discovered a new “feminine hygiene” product being marketed for teen girls. The new vanilla clementine scented wipes and cleansers with confetti-colored packaging and a cute name (OMV!) irked Dr. Gunter because they are designed for girls to use to “freshen” their vaginal area.

Dr. Gunter, a San Francisco-based gynecologist and author of “The Vagina Bible,” has built a reputation as a fierce advocate for women’s health and debunker of pseudoscience. She has called out jade eggs and “detox pearls” and various other items that promise to improve the vagina but that she and other doctors warn could actually be harmful. And, in her view, this product is no different.

She fired off a tweet that became the first volley in a vociferous social media countercampaign: “Hey @vagisil going to call you out here for this predatory line of products aimed at teen girls. Why do you think teen vulvas need special cleaning? To be prepped for men? Because they are dirty. Anxiously awaiting your answer as are all my followers.”

Vagisil responded on Instagram that “we want to clarify any confusion or the underlying belief that OMV! was developed because there is something wrong with teens or that vulvas/vaginas are inherently dirty. That is not the case. All-Day Fresh Wash is an all-over body wash, that is safe, gentle, and pH-balanced for sensitive vulvar area skin.”

Dr. Gunter’s Feb. 4 tweet attracted more than 8,300 likes, 1,300 retweets and hundreds of comments, but that was just the beginning. Dr. Gunter has continued to tweet about the OMV! product line – and has inspired dozens of other gynecologists to join in.
 

‘Your vagina is fine’

Dr. Gunter and other gynecologists have long delivered the message that water alone is sufficient to cleanse the vulvar area and that the vagina itself is self-cleaning. Research into the vaginal microbiome reveals the role of lactobacilli in preventing urogenital diseases. “Disturbances in your vagina microbiome are hard to undo,” says Jocelyn Fitzgerald, MD, a urogynecologist and pelvic reconstructive surgeon at Magee-Womens Hospital at the University of Pittsburgh Medical Center.

To underscore that message, Dr. Fitzgerald recently tweeted in support of Dr. Gunter’s Twitter thread: “Honestly, the @vagisil marketing campaign is a brilliant one because using their products while your vagina is perfectly fine will destroy your microbiome, give you real Bacterial Vaginosis, and prompt you to buy more Vagisil. DON’T FALL FOR IT GIRLS YOUR VAGINA IS FINE.”

In an emailed response to this news organization, a Vagisil spokesperson said, “We follow industry best practices for testing and OMV! products are rigorously assessed for safety and quality. In addition, we work with respected, independent clinical labs that follow strict testing protocols, using board-certified gynecologists and dermatologists to test our products before launch.”

However, beyond the potential for irritation or misuse, the gynecologists zeroed in on the underlying message that girls would feel more confident if they used the wipes and cleanser. For example, the company suggested that teens could use the wipes to get rid of “period funk.”

“There is no such thing as period funk!” gynecologist Danielle Jones, MD, exclaimed in a video on YouTube, where she has a channel called Mama Doctor Jones – with 700,000 subscribers. “All you need is ordinary hygiene. Period funk is not a thing! And if you feel like something is going on because there’s an odor that is abnormal, you need to talk to your doctor.”

Adult women often use wipes and special cleansers in the vaginal area. An online survey of 1,435 Canadian women, published in BMC Women’s Health in 2018, found 42% had used vaginal wipes, 12% had used vaginal washes or cleansers – and 4% had used them internally.

When it launched OMV! in July, Vagisil said it had engaged 2,500 teens and their mothers in creating the product, which it said was “designed to meet the cleansing and care needs of a new generation of young women.”

That extension of a product most commonly used by adult women to teenagers – who often feel self-conscious about their bodies – is exactly what bothers Dr. Gunter. “BTW I am sorry I am subjecting you all to my @vagisil outrage, but preying on teens and amplifying patriarchal shame of normal bodily functions to sell an irritating product is not acceptable. I’m not stopping until they take that OMV! product line down everywhere,” she said in a Feb. 8 tweet that attracted more than 7,900 likes.
 

No ‘glow up’ needed

Dr. Gunter’s tweets tapped into collective anger over the shaming of women’s bodies. The OMV! marketing suggested that teens could get a “glow up” with the products.

“Your vulva doesn’t need a ‘glow up.’ It’s fine like it is. And if it’s not, talk to your doctor,” Dr. Jones said in her Feb. 8 video, which has had almost 350,000 views, with 28,000 likes and only 149 dislikes.

“They’re very clearly pathologizing normal physiology,” Dr. Jones says. “They’re creating language that makes people feel as though their normal bodily functions have to be somehow fixed or changed.”

Dr. Gunter says she specifically wanted to prevent Vagisil from leveraging social media to influence teen girls. With her stream of tweets and support from colleagues around the country, she has sparked a prolonged online conversation.

“I am encouraged by the strong response on social media from both other enraged ob.gyns. and health care professionals as well the response from a lot of women and men,” Dr. Gunter said in an interview. “We have effectively blocked [Vagisil] from using social media.”

In its response to this news organization, Vagisil noted, “We are a brand run by women with daughters of our own.” While defending the products, Vagisil acknowledged the criticisms: “We are always listening to our consumers and our expert partners so that we continuously evolve. We appreciate the perspective that our language choice surrounding periods may perpetuate an old idea and have already begun to make changes to address this.”

Dr. Gunter says she plans to stay on topic. “Given the number of people outraged, I suspect if they venture out on social media again the reaction will be swift,” she said. “Hopefully we have made OMV! toxic for influencers as well.”

In fact, she’s ready to take on “the entire predatory feminine hygiene market. I’m sick of their false claims about balancing pH and not-so-subtle suggestions that vaginas and vulvas and menstruation stink. These products cause psychological harm as well as physical harm from their irritants,” she said.

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

Late one night in early February, Jen Gunter, MD, was scrolling online when she discovered a new “feminine hygiene” product being marketed for teen girls. The new vanilla clementine scented wipes and cleansers with confetti-colored packaging and a cute name (OMV!) irked Dr. Gunter because they are designed for girls to use to “freshen” their vaginal area.

Dr. Gunter, a San Francisco-based gynecologist and author of “The Vagina Bible,” has built a reputation as a fierce advocate for women’s health and debunker of pseudoscience. She has called out jade eggs and “detox pearls” and various other items that promise to improve the vagina but that she and other doctors warn could actually be harmful. And, in her view, this product is no different.

She fired off a tweet that became the first volley in a vociferous social media countercampaign: “Hey @vagisil going to call you out here for this predatory line of products aimed at teen girls. Why do you think teen vulvas need special cleaning? To be prepped for men? Because they are dirty. Anxiously awaiting your answer as are all my followers.”

Vagisil responded on Instagram that “we want to clarify any confusion or the underlying belief that OMV! was developed because there is something wrong with teens or that vulvas/vaginas are inherently dirty. That is not the case. All-Day Fresh Wash is an all-over body wash, that is safe, gentle, and pH-balanced for sensitive vulvar area skin.”

Dr. Gunter’s Feb. 4 tweet attracted more than 8,300 likes, 1,300 retweets and hundreds of comments, but that was just the beginning. Dr. Gunter has continued to tweet about the OMV! product line – and has inspired dozens of other gynecologists to join in.
 

‘Your vagina is fine’

Dr. Gunter and other gynecologists have long delivered the message that water alone is sufficient to cleanse the vulvar area and that the vagina itself is self-cleaning. Research into the vaginal microbiome reveals the role of lactobacilli in preventing urogenital diseases. “Disturbances in your vagina microbiome are hard to undo,” says Jocelyn Fitzgerald, MD, a urogynecologist and pelvic reconstructive surgeon at Magee-Womens Hospital at the University of Pittsburgh Medical Center.

To underscore that message, Dr. Fitzgerald recently tweeted in support of Dr. Gunter’s Twitter thread: “Honestly, the @vagisil marketing campaign is a brilliant one because using their products while your vagina is perfectly fine will destroy your microbiome, give you real Bacterial Vaginosis, and prompt you to buy more Vagisil. DON’T FALL FOR IT GIRLS YOUR VAGINA IS FINE.”

In an emailed response to this news organization, a Vagisil spokesperson said, “We follow industry best practices for testing and OMV! products are rigorously assessed for safety and quality. In addition, we work with respected, independent clinical labs that follow strict testing protocols, using board-certified gynecologists and dermatologists to test our products before launch.”

However, beyond the potential for irritation or misuse, the gynecologists zeroed in on the underlying message that girls would feel more confident if they used the wipes and cleanser. For example, the company suggested that teens could use the wipes to get rid of “period funk.”

“There is no such thing as period funk!” gynecologist Danielle Jones, MD, exclaimed in a video on YouTube, where she has a channel called Mama Doctor Jones – with 700,000 subscribers. “All you need is ordinary hygiene. Period funk is not a thing! And if you feel like something is going on because there’s an odor that is abnormal, you need to talk to your doctor.”

Adult women often use wipes and special cleansers in the vaginal area. An online survey of 1,435 Canadian women, published in BMC Women’s Health in 2018, found 42% had used vaginal wipes, 12% had used vaginal washes or cleansers – and 4% had used them internally.

When it launched OMV! in July, Vagisil said it had engaged 2,500 teens and their mothers in creating the product, which it said was “designed to meet the cleansing and care needs of a new generation of young women.”

That extension of a product most commonly used by adult women to teenagers – who often feel self-conscious about their bodies – is exactly what bothers Dr. Gunter. “BTW I am sorry I am subjecting you all to my @vagisil outrage, but preying on teens and amplifying patriarchal shame of normal bodily functions to sell an irritating product is not acceptable. I’m not stopping until they take that OMV! product line down everywhere,” she said in a Feb. 8 tweet that attracted more than 7,900 likes.
 

No ‘glow up’ needed

Dr. Gunter’s tweets tapped into collective anger over the shaming of women’s bodies. The OMV! marketing suggested that teens could get a “glow up” with the products.

“Your vulva doesn’t need a ‘glow up.’ It’s fine like it is. And if it’s not, talk to your doctor,” Dr. Jones said in her Feb. 8 video, which has had almost 350,000 views, with 28,000 likes and only 149 dislikes.

“They’re very clearly pathologizing normal physiology,” Dr. Jones says. “They’re creating language that makes people feel as though their normal bodily functions have to be somehow fixed or changed.”

Dr. Gunter says she specifically wanted to prevent Vagisil from leveraging social media to influence teen girls. With her stream of tweets and support from colleagues around the country, she has sparked a prolonged online conversation.

“I am encouraged by the strong response on social media from both other enraged ob.gyns. and health care professionals as well the response from a lot of women and men,” Dr. Gunter said in an interview. “We have effectively blocked [Vagisil] from using social media.”

In its response to this news organization, Vagisil noted, “We are a brand run by women with daughters of our own.” While defending the products, Vagisil acknowledged the criticisms: “We are always listening to our consumers and our expert partners so that we continuously evolve. We appreciate the perspective that our language choice surrounding periods may perpetuate an old idea and have already begun to make changes to address this.”

Dr. Gunter says she plans to stay on topic. “Given the number of people outraged, I suspect if they venture out on social media again the reaction will be swift,” she said. “Hopefully we have made OMV! toxic for influencers as well.”

In fact, she’s ready to take on “the entire predatory feminine hygiene market. I’m sick of their false claims about balancing pH and not-so-subtle suggestions that vaginas and vulvas and menstruation stink. These products cause psychological harm as well as physical harm from their irritants,” she said.

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

Late one night in early February, Jen Gunter, MD, was scrolling online when she discovered a new “feminine hygiene” product being marketed for teen girls. The new vanilla clementine scented wipes and cleansers with confetti-colored packaging and a cute name (OMV!) irked Dr. Gunter because they are designed for girls to use to “freshen” their vaginal area.

Dr. Gunter, a San Francisco-based gynecologist and author of “The Vagina Bible,” has built a reputation as a fierce advocate for women’s health and debunker of pseudoscience. She has called out jade eggs and “detox pearls” and various other items that promise to improve the vagina but that she and other doctors warn could actually be harmful. And, in her view, this product is no different.

She fired off a tweet that became the first volley in a vociferous social media countercampaign: “Hey @vagisil going to call you out here for this predatory line of products aimed at teen girls. Why do you think teen vulvas need special cleaning? To be prepped for men? Because they are dirty. Anxiously awaiting your answer as are all my followers.”

Vagisil responded on Instagram that “we want to clarify any confusion or the underlying belief that OMV! was developed because there is something wrong with teens or that vulvas/vaginas are inherently dirty. That is not the case. All-Day Fresh Wash is an all-over body wash, that is safe, gentle, and pH-balanced for sensitive vulvar area skin.”

Dr. Gunter’s Feb. 4 tweet attracted more than 8,300 likes, 1,300 retweets and hundreds of comments, but that was just the beginning. Dr. Gunter has continued to tweet about the OMV! product line – and has inspired dozens of other gynecologists to join in.
 

‘Your vagina is fine’

Dr. Gunter and other gynecologists have long delivered the message that water alone is sufficient to cleanse the vulvar area and that the vagina itself is self-cleaning. Research into the vaginal microbiome reveals the role of lactobacilli in preventing urogenital diseases. “Disturbances in your vagina microbiome are hard to undo,” says Jocelyn Fitzgerald, MD, a urogynecologist and pelvic reconstructive surgeon at Magee-Womens Hospital at the University of Pittsburgh Medical Center.

To underscore that message, Dr. Fitzgerald recently tweeted in support of Dr. Gunter’s Twitter thread: “Honestly, the @vagisil marketing campaign is a brilliant one because using their products while your vagina is perfectly fine will destroy your microbiome, give you real Bacterial Vaginosis, and prompt you to buy more Vagisil. DON’T FALL FOR IT GIRLS YOUR VAGINA IS FINE.”

In an emailed response to this news organization, a Vagisil spokesperson said, “We follow industry best practices for testing and OMV! products are rigorously assessed for safety and quality. In addition, we work with respected, independent clinical labs that follow strict testing protocols, using board-certified gynecologists and dermatologists to test our products before launch.”

However, beyond the potential for irritation or misuse, the gynecologists zeroed in on the underlying message that girls would feel more confident if they used the wipes and cleanser. For example, the company suggested that teens could use the wipes to get rid of “period funk.”

“There is no such thing as period funk!” gynecologist Danielle Jones, MD, exclaimed in a video on YouTube, where she has a channel called Mama Doctor Jones – with 700,000 subscribers. “All you need is ordinary hygiene. Period funk is not a thing! And if you feel like something is going on because there’s an odor that is abnormal, you need to talk to your doctor.”

Adult women often use wipes and special cleansers in the vaginal area. An online survey of 1,435 Canadian women, published in BMC Women’s Health in 2018, found 42% had used vaginal wipes, 12% had used vaginal washes or cleansers – and 4% had used them internally.

When it launched OMV! in July, Vagisil said it had engaged 2,500 teens and their mothers in creating the product, which it said was “designed to meet the cleansing and care needs of a new generation of young women.”

That extension of a product most commonly used by adult women to teenagers – who often feel self-conscious about their bodies – is exactly what bothers Dr. Gunter. “BTW I am sorry I am subjecting you all to my @vagisil outrage, but preying on teens and amplifying patriarchal shame of normal bodily functions to sell an irritating product is not acceptable. I’m not stopping until they take that OMV! product line down everywhere,” she said in a Feb. 8 tweet that attracted more than 7,900 likes.
 

No ‘glow up’ needed

Dr. Gunter’s tweets tapped into collective anger over the shaming of women’s bodies. The OMV! marketing suggested that teens could get a “glow up” with the products.

“Your vulva doesn’t need a ‘glow up.’ It’s fine like it is. And if it’s not, talk to your doctor,” Dr. Jones said in her Feb. 8 video, which has had almost 350,000 views, with 28,000 likes and only 149 dislikes.

“They’re very clearly pathologizing normal physiology,” Dr. Jones says. “They’re creating language that makes people feel as though their normal bodily functions have to be somehow fixed or changed.”

Dr. Gunter says she specifically wanted to prevent Vagisil from leveraging social media to influence teen girls. With her stream of tweets and support from colleagues around the country, she has sparked a prolonged online conversation.

“I am encouraged by the strong response on social media from both other enraged ob.gyns. and health care professionals as well the response from a lot of women and men,” Dr. Gunter said in an interview. “We have effectively blocked [Vagisil] from using social media.”

In its response to this news organization, Vagisil noted, “We are a brand run by women with daughters of our own.” While defending the products, Vagisil acknowledged the criticisms: “We are always listening to our consumers and our expert partners so that we continuously evolve. We appreciate the perspective that our language choice surrounding periods may perpetuate an old idea and have already begun to make changes to address this.”

Dr. Gunter says she plans to stay on topic. “Given the number of people outraged, I suspect if they venture out on social media again the reaction will be swift,” she said. “Hopefully we have made OMV! toxic for influencers as well.”

In fact, she’s ready to take on “the entire predatory feminine hygiene market. I’m sick of their false claims about balancing pH and not-so-subtle suggestions that vaginas and vulvas and menstruation stink. These products cause psychological harm as well as physical harm from their irritants,” she said.

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

Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.

Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.

“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.

Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.

In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.

Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.

Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.

The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
 

More rural women receive long-duration antibiotics

In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).

However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).

The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.

From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.

The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.

However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.

“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
 

Data support need for education and stewardship

“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.

“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.

To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.

The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.

Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.

Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.

“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.

Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.

In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.

Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.

Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.

The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
 

More rural women receive long-duration antibiotics

In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).

However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).

The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.

From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.

The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.

However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.

“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
 

Data support need for education and stewardship

“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.

“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.

To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.

The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.

Women living in rural areas were significantly more likely than were those in urban areas to receive inappropriate antibiotic prescriptions for urinary tract infections, based on data from an observational cohort study of more than 600,000 women.

Uncomplicated urinary tract infections (UTIs) are common among otherwise healthy women in the United States, and certain antibiotics are recommended as first-line therapy, wrote Abbye W. Clark, MD, of Washington University, St. Louis, and colleagues.

“However, the majority of antibiotic prescriptions for uncomplicated UTI are suboptimal because they are written for nonrecommended agents and durations,” they said.

Addressing rural health disparities has become a focus in the United States, and previous studies of respiratory tract infections have shown differences in antibiotic prescribing based on geographic region; “however, no large-scale studies have evaluated rural-urban differences in inappropriate outpatient prescribing for UTI,” they added.

In a study published in Infection Control & Hospital Epidemiology, the researchers identified 670,450 women aged 18-44 years who received oral antibiotics for uncomplicated UTIs between 2010 to 2015, using a commercial insurance database to determine diagnosis and antibiotic prescription information. Women were defined as urban if they lived in a metropolitan statistical area of at least 50,000 inhabitants (86.2%); all other women were defined as rural (13.8%). The median age was 30 years for both groups.

Overall, 46.7% of the women received prescriptions for inappropriate antibiotics, and 76.1% received antibiotics for inappropriate durations.

Antibiotics and durations were defined as appropriate or inappropriate based on current clinical guidelines. “We classified first-line agents (nitrofurantoin, TMP-SMX, fosfomycin) as appropriate and non–first-line agents (fluoroquinolones, beta-lactams) as inappropriate,” the researchers said.

The regimens classified as appropriate duration were “nitrofurantoin 5-day regimen, TMP-SMX (including TMP monotherapy) 3-day regimen, fosfomycin 1-day regimen, fluoroquinolones 3-day regimen, and beta-lactams 3- to 7-day regimen. All other regimens were classified as inappropriate duration,” they noted.
 

More rural women receive long-duration antibiotics

In a multivariate analysis, similar percentages of antibiotics for rural and urban women consisted of inappropriate agents (45.9% vs. 46.9%) including use of fluoroquinolones (41.0% vs. 41.7%) and beta-lactams (4.8% vs. 5.0%).

However, across all antibiotics, women in rural areas were more likely than were women in urban areas to receive prescriptions for inappropriately long durations (83.9% vs. 75.9%, adjusted risk ratio 1.10).

The percentage of women who received inappropriate antibiotic agents was not significantly different based on geographic region of the country.

From 2011 to 2015, the quarterly proportion of women overall who received inappropriate agents and antibiotics for inappropriate durations decreased slightly (48.5% to 43.7% and 78.3% to 73.4%, respectively), the researchers noted.

The study findings were limited by several factors including the potentially lenient definition of antibiotic duration, a study population that disproportionately oversampled from the South and undersampled from the West, use of ZIP codes to determine rural vs. urban status, lack of data on race and income, and lack of access to urine culture results, the researchers noted.

However, “our study identified rural-urban differences in antibiotic prescribing, including an actionable disparity in the duration of antibiotics that disproportionately affects women who live in rural locations,” they said.

“Given the large quantity of inappropriate prescriptions annually in the U.S., as well as the negative patient- and society-level consequences of unnecessary exposure to antibiotics, antimicrobial stewardship interventions are needed to improve outpatient UTI antibiotic prescribing, particularly in rural settings,” they concluded.
 

Data support need for education and stewardship

“This manuscript provides valuable information to all women’s health providers regarding the importance of antibiotic stewardship,” David M. Jaspan, DO, and Natasha Abdullah, MD, Einstein Medical Center, Philadelphia, said in an interview. Whether urban or rural, over 45% of the patients received inappropriate non–first-line treatment and 76% of the prescriptions were for an inappropriate duration (98.8% for longer than recommended), they emphasized.

“The potential negative impact of antibiotic resistance, coupled with the potential for increased side effects, should prompt providers to ensure that when treating uncomplicated UTIs in women, that the choice of treatment and the duration of treatment is tailored to the patient’s needs,” the Dr. Jaspan and Dr. Abdullah said.

To improve antibiotic prescribing, especially at the local and regional level, “We encourage providers to familiarize themselves with local information as it pertains to known resistance when prescribing empiric treatment regimens for uncomplicated UTIs,” they said.

The study was supported by the National Center for Advancing Translational Sciences at the National Institutes of Health. Lead author Dr. Clark, as well as Dr. Jaspan and Dr. Abdullah, had no financial conflicts to disclose.

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

.

In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

.

In recent decades, natural products have had increased consumer attention in industrialized nations. One of the challenges is that “natural” can be more of a perception than a standard. “Herbal products” is a more frequently used and perhaps a more apt term. Herbal products come in many forms, including herbs used in food preparation, teas, infusions, caplets, dried extracts, essential oils, and tinctures.

Multiple prescription medications have pharmacologically active compounds that originated from herbal products, both historically and currently. Examples include the cardiac stimulant digoxin (foxglove plant), the antimalarial quinine (Cinchona bark), and antihypertensives (Rauwolfia serpentina). Indeed, the first pharmacologically active compound, morphine, was extracted from the seed pods of opium poppies approximately 200 years ago. This demonstrated that medications could be purified from plants and that a precise dose could be determined for administration. However, herbal products are grown and harvested in varying seasonal conditions and soil types, which, over time and geography, may contribute to variability in the levels of active compound in the final products.

The importance of active compound purification and consistent precise dosage in herbal products brings up the topic of regulation. Herbal products are considered dietary supplements and as such are Food and Drug Administration regulated as a food under the 1994 Dietary Supplement Health Education Act. Regulation as a food product does not involve the same level of scrutiny as a medication. There is no requirement that manufacturers check for purity and consistency of their product’s active compound(s). Manufacturers must ensure that the claims they make about herbal products are not false or misleading. They must also support their claims with evidence. However, there is no requirement for the manufacturers to submit this evidence to the FDA. This can translate into a discrepancy between the claim on the product label and scientific evidence that the product does what it claims to do. In other words, the product may not be effective.

With uncertain efficacy, the safety of herbal products comes into focus. Very few herbal products (or their specific active compounds) have been scientifically studied for safety in pregnancy and lactation. Further, herbal products may contain contaminants. Metals such as lead and mercury occur naturally. Yet, because of human activities, both may have collected in areas where herbal products are grown. From a safety perspective, both can be concerning in pregnancy or lactation. Lead and mercury are two examples of metal contaminants. Other contaminants may include pesticides, chemicals, and bacteria or other microorganisms. Some liquid herbal products such as tinctures contain alcohol, which should be avoided in pregnancy. An additional consideration would be the potential for herbal products, including any of their known or unknown product contents, to interact with prescribed medications or anesthesia.
 

Select examples of herbal products

Astragalus is the root of an herb and it is used for reasons of boosting immunity, energy, and other functions. These and its purported promotion of breast milk flow (galactagogue) are unsupported. Safety concerns include irregular heartbeat and dizziness, rendering it unsafe for use in pregnancy and of unknown efficacy and safety in lactation.

Kombucha is an herbal product made from leaves (tea), sugar, a culture, and other varying products. Like many herbal products, it is both manufactured and home brewed. It is used for probiotic and antioxidant reasons. As a fermented product, kombucha may contain 0.2%-0.5% alcohol. There is no known safe level of alcohol and no known safe type of alcohol for use in pregnancy. Alcohol exposure in pregnancy can result in fetal alcohol spectrum disorders, involving a range of birth defects and life-long intellectual, learning and behavioral disorders. Alcohol found in breast milk approximates the level of alcohol found in the maternal bloodstream. Alcohol-containing products should be avoided in pregnancy and lactation.

Nux vomica is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. It comes from the raw seeds (toxic) of an evergreen tree. It has serious safety concerns and yet it is still in use. It contains strychnine, which can harm both the pregnant individual and the developing fetus. It is not recommended in lactation.

Red raspberry leaf is a leaf, brewed and ingested as a tea. It is used for reasons of preventing miscarriage, relieving nausea and stomach discomfort, toning the uterus, reducing labor pain, increasing breast milk production, and other functions. In low doses, it appears to be safe. In high doses, it can induce smooth muscle relaxation. Efficacy has not been demonstrated with labor and delivery or in increasing breast milk production.

Tabacum is an herbal product and is used for reasons of reducing nausea or vomiting in pregnancy. Its full name is Nicotiana tabacum (tobacco) and it contains 2%-8% nicotine, which should be avoided in pregnancy. Nicotine is a health danger for the pregnant individual and can damage a developing fetus’ brain and lungs.

Unless otherwise scientifically demonstrated, herbal products should be considered medications with pharmacologic activity, potential adverse effects, and potential toxicity in pregnancy and lactation. It’s easy for a patient to forget about reporting any nonprescription medications during a patient-provider visit. As a provider, purposefully asking about all over-the-counter and herbal products during each visit can prompt the patient to provide this important information. Further, it may facilitate discussion about the continuation/discontinuation of products of unknown safety and unknown benefit, culminating in the serious reflection: “Is it really worth the risk?”

For further information about the safety of herbal products, consult local Poison Control Centers, MothertoBaby, MothertoBaby affiliates, and the National Institutes of Health Drugs and Lactation Database, LactMed.

Dr. Hardy is a consultant on global maternal-child health and pharmacoepidemiology, and represents the Society for Birth Defects Research and Prevention and the Organization of Teratology Information Specialists at PRGLAC meetings. Dr. Hardy has worked with multiple pharmaceutical manufacturers regarding studies of medication safety in pregnancy, most recently Biohaven Pharmaceuticals, New Haven, CT.

.

Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Use of prophylactic negative pressure wound therapy may not be appropriate in surgical cases where women undergo a laparotomy for presumed gynecologic malignancy, according to recent research in Obstetrics & Gynecology.

“The results of our randomized trial do not support the routine use of prophylactic negative pressure wound therapy at the time of laparotomy incision closure in women who are undergoing surgery for gynecologic malignancies or in morbidly obese women who are undergoing laparotomy for benign indications,” Mario M. Leitao Jr., MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote.

Dr. Leitao and colleagues randomized 663 patients, stratified by body mass index (BMI) after skin closure, to receive negative pressure wound therapy (NPWT) or standard gauze after undergoing a laparotomy for gynecological surgery between March 2016 and August 2019. Patients in the study were aged a median 61 years with a median BMI of 26 kg/m², but 32 patients with a BMI of 40 or higher who underwent a laparotomy for gynecologic surgery regardless of indication were also included in the study. Most women (80%-82%) were undergoing surgery to treat ovary, fallopian tube, or peritoneal cancer. The most common medical comorbidities in both groups were hypertension (34%-35%) and diabetes (8%-14%). Information on race of patients was not included in the baseline characteristics for the study.

In total, 505 patients were available for evaluation after surgery, which consisted of 254 patients in the NPWT group and 251 patients in the standard gauze group, with 495 patients (98%) having a malignant indication. The researchers examined the incidence of wound complication up to 30 days after surgery.

The results showed a similar rate of wound complications in the NPWT group (44 patients; 17.3%), compared with the group receiving standard gauze (41 patients; 16.3%), with an absolute risk difference between groups of 1% (90% confidence interval, –4.5 to 6.5%; P = .77). Nearly all patients who developed wound complications in both NPWT (92%) and standard gauze (95%) groups had the wound complication diagnosis occur after discharge from the hospital. Dr. Leitao and colleagues noted similarities between groups with regard to wound complications, with most patients having grade 1 complications, and said there were no instances of patients requiring surgery for complications. Among patients in the NPWT group, 33 patients developed skin blistering, compared with 3 patients in the standard gauze group (13% vs. 1.2%; P < .001). After an interim analysis consisting of 444 patients, the study was halted because of “low probability of showing a difference between the two groups at the end of the study.”

The analysis of patients with a BMI of 40 or higher showed 7 of 15 patients (47%) developed wound complications in the NPWT group and 6 of 17 patients (35%) in the standard gauze group (P = .51). In post hoc analyses, the researchers found a median BMI of 26 (range, 17-60) was significantly associated with not developing a wound complication, compared with a BMI of 32 (range, 17-56) (P < .001), and that 41% of patients with a BMI of at least 40 experienced wound complications, compared with 15% of patients with a BMI of less than 40 (P < .001). There was an independent association between developing a wound complication and increasing BMI, according to a multivariate analysis (adjusted odds ratio, 1.10; 95% CI, 1.06-1.14).
 

Applicability of results unclear for patients with higher BMI

Sarah M. Temkin, MD, a gynecologic oncologist who was not involved with the study, said in an interview that the results by Dr. Leitao and colleagues answer the question of whether patients undergoing surgery for gynecologic malignancy require NPWT, but raised questions about patient selection in the study.

“I think it’s hard to take data from this type of high-end surgical practice and apply it to the general population,” she said, who noted the median BMI of 26 for patients included in the study. A study that included only patients with a BMI of 40 or higher “would have made these results more applicable.”

The low rate of wound complications in the study could potentially be explained by patient selection, Dr. Temkin explained. She cited her own retrospective study from 2016 that showed a wound complication rate of 27.3% for patients receiving prophylactic NPWT where the BMI for the group was 41.29, compared with a complication rate of 19.7% for patients receiving standard care who had a BMI of 30.67.

“It’s hard to cross-trial compare, but that’s significantly higher than what they saw in this prospective study, and I would say that’s a difference with the patient population,” she said. “I think the question of how to reduce surgical-site infections and wound complications in the heavy patient with comorbidities is still unanswered.”

The question is important because patients with a higher BMI and medical comorbidities “still need cancer surgery and methods to reduce the morbidity of that surgery,” Dr. Temkin said. “I think this is an unmet need.”

This study was funded in part by a support grant from the National Institutes of Health/National Cancer Institute Cancer Center, and KCI/Acelity provided part of the study protocol. Nine authors reported personal and institutional relationships in the form of personal fees, grants, stock ownership, consultancies, and speaker’s bureau positions with AstraZeneca, Biom’Up, Bovie Medical, C Surgeries, CMR, ConMed, Covidien, Ethicon, GlaxoSmithKline, GRAIL, Intuitive Surgical, JNJ, Medtronic, Merck, Mylan, Olympus, Stryker/Novadaq, TransEnterix, UpToDate, and Verthermia. Dr. Temkin reported no relevant financial disclosures.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.