Women's Health

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

FatCamera/E+/Getty Images

Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

FatCamera/E+/Getty Images

Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.

WASHINGTON – Cardiovascular risk factors may be elevated “as soon as the first postpartum year” in women who have gestational diabetes or hypertensive disorders of pregnancy, recent findings have affirmed, Deborah B. Ehrenthal, MD, MPH, said at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

FatCamera/E+/Getty Images

Dr. Ehrenthal was one of several researchers who urged innovative strategies and improved care coordination to boost women’s follow-up after gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes and complications. “The metabolic stress of pregnancy can uncover underlying susceptibilities,” she said. “And adverse pregnancy outcomes can have long-lasting residual effects.”

Evidence that adverse pregnancy outcomes – including GDM and hypertensive disorders of pregnancy (HDP) – can elevate cardiovascular risk comes most recently from the Nulliparous Pregnancy Outcomes Study – Monitoring Mothers to be Heart Health Study (nuMoM2b–HHS study), a prospective observational cohort that followed 4,484 women 2-7 years after their first pregnancy. Women had a follow-up exam, with blood pressure and anthropometric measurements and clinical/biological testing, an average of 3 years post partum.

An analysis published in October 2019 in the Journal of the American Heart Association shows that women with HDP (including preeclampsia and gestational hypertension) had a relative risk of hypertension of 2.5 at follow-up, compared with women without HDP. Women who had preeclampsia specifically were 2.3 times as likely as were women who did not have preeclampsia to have incident hypertension at follow-up, said Dr. Ehrenthal, a coinvestigator of the study.

The analysis focused on incident hypertension as the primary outcome, and adjusted for age, body mass index, and other important cardiovascular disease risk factors, she noted. Researchers utilized the diagnostic threshold for hypertension extant at the time of study design: A systolic blood pressure of 140 mm Hg or greater, or a diastolic BP of 90 mm Hg or greater (J Am Heart Assoc. 2019;8:e013092).

HDP was the most common adverse pregnancy outcome in the nuMoM2b–HHS study (14%). Among all participants, 4% had GDM. Approximately 82% had neither HDP nor GDM. Other adverse pregnancy outcomes included in the analysis were preterm birth, small-for-gestational-age birth, and stillbirth.

Additional preliminary estimates presented by Dr. Ehrenthal show that, based on the new (2017) lower threshold for hypertension – 130 mg Hg systolic or 80 mm Hg diastolic – the disorder afflicted 37% of women who had experienced HDP (relative risk 2.1), and 32% of women who had GDM (RR 1.8). Prediabetes/diabetes (using a fasting blood glucose threshold of 100 mg/dL) at follow-up affected an estimated 21% of women who had HDP (RR 1.4) and 38% of women who had GDM (RR 2.5).

Notably, across the entire study cohort, 20% had hypertension at follow-up, “which is extraordinary” considering the short time frame from pregnancy and the young age of the study population – a mean maternal age of 27 years, said Dr. Ehrenthal, associate professor of population health sciences and obstetrics & gynecology at the University of Wisconsin, Madison.

Also across the cohort, 15% had prediabetes/diabetes at follow-up. “We need to think about women more generally,” she cautioned. “While we recognize the significant elevated risk of HDP and GDM [for the development of subsequent hypertension and cardiovascular risk], we will miss a lot of women [if we focus only on the history of HDP and GDM.]”

The majority of women found to have hypertension or prediabetes/diabetes at follow-up had experienced neither HDP nor GDM, but a good many of them (47% of those who had hypertension and 47% of those found to have prediabetes/diabetes) had a BMI of 30 or above, Dr. Ehrenthal said at the DPSG-NA meeting.
 

Nurses Health Study, hyperglycemia and adverse pregnancy outcome follow-up data

The new findings from the nuMoM2b–HHS study add to a robust and growing body of evidence that pregnancy is an important window to future health, and that follow up and screening after GDM and HDP are crucial.

Regarding GDM specifically, “there’s quite a bit of literature by now demonstrating that GDM history is a risk factor for hypertension, even 1-2 years post partum, and that the risk is elevated as well for dyslipidemia and vascular dysfunction,” Deirdre K. Tobias, D.Sc., an epidemiologist at Brigham and Women’s Hospital and assistant professor of nutrition at Harvard TH Chan School of Public Health, Boston, said at the DPSG meeting.

An analysis of the Nurses Health Study II (NHS II) cohort published in 2017 found a 40% higher relative risk of cardiovascular disease events (largely myocardial infarction) in women who had GDM, compared with women who did not have GDM over a median follow-up of 26 years. This was after adjustments were made for age, time since pregnancy, menopausal status, family history of MI or stroke, hypertension in pregnancy, white race/ethnicity, prepregnancy BMI, and other factors (JAMA Intern Med. 2017;177[12]:1735-42).

The NHS data also have shown, however, that the elevated risk for cardiovascular disease after a GDM pregnancy “can be mitigated by adopting a healthy lifestyle,” said Dr. Tobias, lead author of the 2017 NHS II analysis. Adjustments for postpregnancy weight gain and lifestyle factors attenuated the relative risk of cardiovascular disease events after a GDM pregnancy to a 30% increased risk.

Dr. Tobias and colleagues currently are looking within the NHS cohort for “metabolomic signatures” or signals – various amino acid and lipid metabolites – to identify the progression of GDM to type 2 diabetes. Metabolomics “may help further refine our understanding of the long-term links between GDM and prevention of type 2 diabetes and of cardiovascular disease in mothers,” she said.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-Up Study, in the meantime, is documenting associations of maternal glucose levels during pregnancy not only with prediabetes or type 2 diabetes 10-14 years later, but also with measures of cardiovascular risk in mothers 10-14 years later.

Just as perinatal outcomes were strongly associated with glucose as a continuous variable in the original HAPO study, “it’s clear there’s a progressive increase in the risk of [later] disorders of glucose metabolism as [fasting blood glucose levels and 1- and-2-hour glucose values] in pregnancy are higher,” said Boyd E. Metzger, MD, the Tom D. Spies emeritus professor of metabolism and nutrition at Northwestern University, Chicago, and principal investigator of the original HAPO study and its follow up.

“Another message is that the more normal you are in pregnancy, the more normal you will be many years later. Good values [during pregnancy] produce good outcomes.”

Currently unpublished data from the HAPO Follow-Up Study are being analyzed, but it appears thus far that GDM is not associated with hypertension (per the old diagnostic threshold) in this cohort after adjustment for maternal age, BMI, smoking, and family history of hypertension. GDM appears to be a significant risk factor for dyslipidemia, however. HDL cholesterol at follow-up was significantly lower for mothers who had GDM compared with those without, whereas LDL cholesterol and triglycerides at follow-up were significantly higher for mothers with GDM, Dr. Metzger said.
 

Racial/ethnic disparities, postpartum care

Neither long-term study – the NHS II or the HAPO Follow-Up Study – has looked at racial and ethnic differences. The HAPO cohort is racially-ethnically diverse but the NHS II cohort is predominantly white women.

Research suggests that GDM is a heterogeneous condition with some unique phenotypes in subgroups that vary by race and ethnicity. And just as there appear to be racial-ethnic differences in the pathophysiology of GDM, there appear to be racial-ethnic differences in the progression to type 2 diabetes – a known risk factor for cardiovascular disease, said Monique Henderson, PhD, a research scientist at Kaiser Permanente Northern California (KPNC).

On the broadest level, while Asian Americans have the highest prevalence of GDM, African Americans have the highest rates of progressing to type 2 diabetes, Dr. Henderson said. Disparities “may [stem from] metabolic differences in terms of insulin resistance and secretion that are different between pregnancy and the postpartum period, and that might vary [across racial-ethnic subgroups],” she said. Lifestyle differences and variation in postpartum screening rates also may play a role.

At KPNC, where women with GDM receive calls and letters reminding them of the need for postpartum screening, only 48% overall completed an oral glucose tolerance test at 4-12 weeks post partum, as recommended by both the American Diabetes Association and the American College of Obstetricians and Gynecologists. Both before and after adjustment for education, attendance at a postpartum visit, and other variables, Chinese women were most likely to have screening, and black women were least likely, said Dr. Henderson, referring to ongoing research.

A study Dr. Ehrenthal led of women with GDM or HDP recruited from the postpartum service of a large community-based, academic obstetrical hospital in Delaware showed that while nearly all women attended a 6-week postpartum visit with their ob.gyns., 59% of women with GDM had not yet completed diabetes screening when they were interviewed 3 months post partum. Most women with HDP indicated they had follow-up blood pressure testing, and just over half of women with either diagnosis recalled having ever had lipid testing (J Women’s Health 2014;23[9]:760-4).

Women least likely to complete screening tests were those who had no college education, those who had less than a high school level of health literacy, and those who were not privately insured, Dr. Ehrenthal said.

A large national study of privately insured women also found low rates of follow-up testing, however. While the majority of women with GDM had a postpartum visit with an obstetrician or primary care physician within a year after delivery, only a minority of women had a glycemic screening test completed (Obstet Gynecol. 2016;128[1]:159-67).

“We can’t place the blame on women,” Dr. Ehrenthal said. “We need increased attention to screening,” including screening for cardiovascular disease risk factors, and a “deliberate hand-off to primary care.”

For follow-up cardiovascular disease risk factor assessment after HDP, ACOG recommends periodic (perhaps annually) assessment and referral for treatment as needed, and the cardiology professional organizations recommend that pregnancy history be considered when assessing risk in order to decide on lipid treatment, she noted.

Each of the speakers reported that they have no financial or other interests that pose a conflict of interest. The HAPO Follow-Up Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, and the nuMoM2b–HHS study has been funded by several National Institutes of Health institutes and other programs and initiatives.

VANCOUVER – Presurgical ultrasound does a good job predicting advanced versus early American Society of Reproductive Medicine endometriosis stage, and that can help ensure that a patient gets to the right surgeon.

Researchers retrospectively collected data from ultrasounds, using it to create an ASRM stage, and compared the results with the stage seen at surgery. “We’re very good at telling people what they should expect at surgery,” said Mathew Leonardi, MD, who is a gynecologist at the University of Sydney’s Nepean Hospital.

The researchers conducted the study because of perceived mistrust among surgeons when it comes to presurgical imaging. “There is still a lot of cynicism and a lot of hesitancy to adopt this,” Dr. Leonardi said at the meeting sponsored by AAGL. He was unapologetic about the activist nature of the research. “We thought, what better way [to convince surgeons] than to produce an ultrasound-based ASRM scoring system to then match to the surgical findings, because if we can predict the ASRM score preoperatively, there may be more buy-in by the surgeons for the value of imaging.”

He noted that surgeons differ in their training, so getting the patient to the right surgeon is critical. “If you go to a gynecologist who is not minimally invasive trained, you may [end up with] an abandoned surgery, or an incomplete surgical excision leading to residual disease. So being able to predict the severity of the disease preoperatively, you can allow the patient to get to the right surgeon with the right team members.”

The analysis included 204 procedures performed between January 2016 and April 2018. Participants underwent deep endometriosis transvaginal ultrasound at one of two tertiary referral service centers, and laparoscopy by surgeons in the Sydney metropolitan area. Each case was received as a ASRM score of 0-4 at both ultrasound and surgery, and scores of 0-2 and 3-4 were grouped together for analysis.

“We grouped patients that have ASRM 3-4 into one group and those who have less than that [into another group], because clinically that seems to be where the most practical divide is,” said Dr. Leonardi.

It was difficult to differentiate individual ASRM stages from one another using ultrasound, but the technique performed much better in the combined analysis. In assigning a patient to the ASRM stage 0-2 endometriosis group, it had 94.9% sensitivity and 93.8% specificity, and for assigning to ASRM stage 3-4, it had values of 93.8% and 94.9%, respectively.

The success is encouraging, but there is more work to be done. “We are going to have to differentiate those with early-stage endometriosis or stage 1-2, and those that are negative. We are working on being able to identify superficial endometriosis noninvasively, but for now, as a triaging tool ultrasound can get the patient to the right surgeon,” Dr. Leonardi said.

Dr. Leonardi reported no relevant financial disclosures

VANCOUVER – Presurgical ultrasound does a good job predicting advanced versus early American Society of Reproductive Medicine endometriosis stage, and that can help ensure that a patient gets to the right surgeon.

Researchers retrospectively collected data from ultrasounds, using it to create an ASRM stage, and compared the results with the stage seen at surgery. “We’re very good at telling people what they should expect at surgery,” said Mathew Leonardi, MD, who is a gynecologist at the University of Sydney’s Nepean Hospital.

The researchers conducted the study because of perceived mistrust among surgeons when it comes to presurgical imaging. “There is still a lot of cynicism and a lot of hesitancy to adopt this,” Dr. Leonardi said at the meeting sponsored by AAGL. He was unapologetic about the activist nature of the research. “We thought, what better way [to convince surgeons] than to produce an ultrasound-based ASRM scoring system to then match to the surgical findings, because if we can predict the ASRM score preoperatively, there may be more buy-in by the surgeons for the value of imaging.”

He noted that surgeons differ in their training, so getting the patient to the right surgeon is critical. “If you go to a gynecologist who is not minimally invasive trained, you may [end up with] an abandoned surgery, or an incomplete surgical excision leading to residual disease. So being able to predict the severity of the disease preoperatively, you can allow the patient to get to the right surgeon with the right team members.”

The analysis included 204 procedures performed between January 2016 and April 2018. Participants underwent deep endometriosis transvaginal ultrasound at one of two tertiary referral service centers, and laparoscopy by surgeons in the Sydney metropolitan area. Each case was received as a ASRM score of 0-4 at both ultrasound and surgery, and scores of 0-2 and 3-4 were grouped together for analysis.

“We grouped patients that have ASRM 3-4 into one group and those who have less than that [into another group], because clinically that seems to be where the most practical divide is,” said Dr. Leonardi.

It was difficult to differentiate individual ASRM stages from one another using ultrasound, but the technique performed much better in the combined analysis. In assigning a patient to the ASRM stage 0-2 endometriosis group, it had 94.9% sensitivity and 93.8% specificity, and for assigning to ASRM stage 3-4, it had values of 93.8% and 94.9%, respectively.

The success is encouraging, but there is more work to be done. “We are going to have to differentiate those with early-stage endometriosis or stage 1-2, and those that are negative. We are working on being able to identify superficial endometriosis noninvasively, but for now, as a triaging tool ultrasound can get the patient to the right surgeon,” Dr. Leonardi said.

Dr. Leonardi reported no relevant financial disclosures

VANCOUVER – Presurgical ultrasound does a good job predicting advanced versus early American Society of Reproductive Medicine endometriosis stage, and that can help ensure that a patient gets to the right surgeon.

Researchers retrospectively collected data from ultrasounds, using it to create an ASRM stage, and compared the results with the stage seen at surgery. “We’re very good at telling people what they should expect at surgery,” said Mathew Leonardi, MD, who is a gynecologist at the University of Sydney’s Nepean Hospital.

The researchers conducted the study because of perceived mistrust among surgeons when it comes to presurgical imaging. “There is still a lot of cynicism and a lot of hesitancy to adopt this,” Dr. Leonardi said at the meeting sponsored by AAGL. He was unapologetic about the activist nature of the research. “We thought, what better way [to convince surgeons] than to produce an ultrasound-based ASRM scoring system to then match to the surgical findings, because if we can predict the ASRM score preoperatively, there may be more buy-in by the surgeons for the value of imaging.”

He noted that surgeons differ in their training, so getting the patient to the right surgeon is critical. “If you go to a gynecologist who is not minimally invasive trained, you may [end up with] an abandoned surgery, or an incomplete surgical excision leading to residual disease. So being able to predict the severity of the disease preoperatively, you can allow the patient to get to the right surgeon with the right team members.”

The analysis included 204 procedures performed between January 2016 and April 2018. Participants underwent deep endometriosis transvaginal ultrasound at one of two tertiary referral service centers, and laparoscopy by surgeons in the Sydney metropolitan area. Each case was received as a ASRM score of 0-4 at both ultrasound and surgery, and scores of 0-2 and 3-4 were grouped together for analysis.

“We grouped patients that have ASRM 3-4 into one group and those who have less than that [into another group], because clinically that seems to be where the most practical divide is,” said Dr. Leonardi.

It was difficult to differentiate individual ASRM stages from one another using ultrasound, but the technique performed much better in the combined analysis. In assigning a patient to the ASRM stage 0-2 endometriosis group, it had 94.9% sensitivity and 93.8% specificity, and for assigning to ASRM stage 3-4, it had values of 93.8% and 94.9%, respectively.

The success is encouraging, but there is more work to be done. “We are going to have to differentiate those with early-stage endometriosis or stage 1-2, and those that are negative. We are working on being able to identify superficial endometriosis noninvasively, but for now, as a triaging tool ultrasound can get the patient to the right surgeon,” Dr. Leonardi said.

Dr. Leonardi reported no relevant financial disclosures

VANCOUVER – In patients undergoing hysterectomy, preoperative depression is associated with an increased risk of first-time persistent opioid use after surgery.

Liderina/Thinkstock

Women with depression had an 8% increased risk of perioperative opioid use but a 43% increased risk of persistent use, defined as at least one perioperative prescription followed by at least one prescription 90 days or longer after surgery.

Opioid prescriptions after surgery have been on the rise in recent years, and this has led to a focus on how chronic pain disorders are managed. But studies have shown that patients undergoing general surgery, both minor and major, are at increased risk of persistent opioid use, even after a single surgery, according to Erin Carey, MD, director of the division of minimally invasive gynecologic surgery at the University of North Carolina at Chapel Hill, who presented the research at the meeting sponsored by AAGL.

“We also know that preoperative depression has been linked to adverse outcomes after hysterectomy, both acute postoperative pain in the first 2 days after surgery, and increasing the risk of chronic postoperative pain,” Dr. Carey said.

That prompted her and her team to look at whether preoperative depression might influence the risk of new persistent opioid use after hysterectomy. They analyzed data from the IBM Watson/Truven Health Analytics MarketScan database of claims-based data, which collects information from a variety of sources, including electronic medical records and workplace records such as absences, disability, and long-term disability.

“So it does allow for long-term tracking, which makes it optimal for this type of study,” said Dr. Carey.

The study included 382,078 hysterectomies performed between 2001 and 2015 on women who had continuous prescription plans 180 days before to 180 days after the procedure, excluding anyone who had an opioid prescription in the previous 180 days; 60% of the procedures were minimally invasive. About 20% of women were considered to have depression before the procedure, based on a diagnosis (55%), an antidepressant prescription (22%), or both (23%).

There were some differences at baseline between the two populations: Women with preoperative depression were more likely to have a comorbid pain disorder, compared with patients without depression (20% vs. 14%), another psychiatric disorder (2% vs. less than 1%), and a Charlson comorbidity (12% vs. 9%). They also were less likely to undergo a minimally invasive procedure than women without depression (66% vs. 79%). There was an increase in the prevalence of depression over time, from 16% to 23%.

Overall, 74% of women were prescribed an opioid during the perioperative period; 17% were filled before the hysterectomy was performed. Preoperative fills also increased over time, from 4% in 2001 to 21% in 2015.

Women with preoperative depression were at a slightly greater risk for perioperative opioid use (risk ratio, 1.08), but a greater risk for persistent postoperative opioid use (11% vs. 8%; RR, 1.43). The heightened risk for opioid use was similar whether the surgery was performed on an outpatient or inpatient basis.

The presence of other comorbidities in women with diagnosed depression or prescribed antidepressants complicates the findings, according to Dr. Carey. “There may be additional chronic pain factors that are confounding this data, but it is consistent with other data that de novo postoperative opioid dependence may be a higher risk for these patients, so it’s important for us to look at that critically.”

Dr. Carey has been a consultant for Teleflex Medical and a speaker for Med-IQ.

VANCOUVER – In patients undergoing hysterectomy, preoperative depression is associated with an increased risk of first-time persistent opioid use after surgery.

Liderina/Thinkstock

Women with depression had an 8% increased risk of perioperative opioid use but a 43% increased risk of persistent use, defined as at least one perioperative prescription followed by at least one prescription 90 days or longer after surgery.

Opioid prescriptions after surgery have been on the rise in recent years, and this has led to a focus on how chronic pain disorders are managed. But studies have shown that patients undergoing general surgery, both minor and major, are at increased risk of persistent opioid use, even after a single surgery, according to Erin Carey, MD, director of the division of minimally invasive gynecologic surgery at the University of North Carolina at Chapel Hill, who presented the research at the meeting sponsored by AAGL.

“We also know that preoperative depression has been linked to adverse outcomes after hysterectomy, both acute postoperative pain in the first 2 days after surgery, and increasing the risk of chronic postoperative pain,” Dr. Carey said.

That prompted her and her team to look at whether preoperative depression might influence the risk of new persistent opioid use after hysterectomy. They analyzed data from the IBM Watson/Truven Health Analytics MarketScan database of claims-based data, which collects information from a variety of sources, including electronic medical records and workplace records such as absences, disability, and long-term disability.

“So it does allow for long-term tracking, which makes it optimal for this type of study,” said Dr. Carey.

The study included 382,078 hysterectomies performed between 2001 and 2015 on women who had continuous prescription plans 180 days before to 180 days after the procedure, excluding anyone who had an opioid prescription in the previous 180 days; 60% of the procedures were minimally invasive. About 20% of women were considered to have depression before the procedure, based on a diagnosis (55%), an antidepressant prescription (22%), or both (23%).

There were some differences at baseline between the two populations: Women with preoperative depression were more likely to have a comorbid pain disorder, compared with patients without depression (20% vs. 14%), another psychiatric disorder (2% vs. less than 1%), and a Charlson comorbidity (12% vs. 9%). They also were less likely to undergo a minimally invasive procedure than women without depression (66% vs. 79%). There was an increase in the prevalence of depression over time, from 16% to 23%.

Overall, 74% of women were prescribed an opioid during the perioperative period; 17% were filled before the hysterectomy was performed. Preoperative fills also increased over time, from 4% in 2001 to 21% in 2015.

Women with preoperative depression were at a slightly greater risk for perioperative opioid use (risk ratio, 1.08), but a greater risk for persistent postoperative opioid use (11% vs. 8%; RR, 1.43). The heightened risk for opioid use was similar whether the surgery was performed on an outpatient or inpatient basis.

The presence of other comorbidities in women with diagnosed depression or prescribed antidepressants complicates the findings, according to Dr. Carey. “There may be additional chronic pain factors that are confounding this data, but it is consistent with other data that de novo postoperative opioid dependence may be a higher risk for these patients, so it’s important for us to look at that critically.”

Dr. Carey has been a consultant for Teleflex Medical and a speaker for Med-IQ.

VANCOUVER – In patients undergoing hysterectomy, preoperative depression is associated with an increased risk of first-time persistent opioid use after surgery.

Liderina/Thinkstock

Women with depression had an 8% increased risk of perioperative opioid use but a 43% increased risk of persistent use, defined as at least one perioperative prescription followed by at least one prescription 90 days or longer after surgery.

Opioid prescriptions after surgery have been on the rise in recent years, and this has led to a focus on how chronic pain disorders are managed. But studies have shown that patients undergoing general surgery, both minor and major, are at increased risk of persistent opioid use, even after a single surgery, according to Erin Carey, MD, director of the division of minimally invasive gynecologic surgery at the University of North Carolina at Chapel Hill, who presented the research at the meeting sponsored by AAGL.

“We also know that preoperative depression has been linked to adverse outcomes after hysterectomy, both acute postoperative pain in the first 2 days after surgery, and increasing the risk of chronic postoperative pain,” Dr. Carey said.

That prompted her and her team to look at whether preoperative depression might influence the risk of new persistent opioid use after hysterectomy. They analyzed data from the IBM Watson/Truven Health Analytics MarketScan database of claims-based data, which collects information from a variety of sources, including electronic medical records and workplace records such as absences, disability, and long-term disability.

“So it does allow for long-term tracking, which makes it optimal for this type of study,” said Dr. Carey.

The study included 382,078 hysterectomies performed between 2001 and 2015 on women who had continuous prescription plans 180 days before to 180 days after the procedure, excluding anyone who had an opioid prescription in the previous 180 days; 60% of the procedures were minimally invasive. About 20% of women were considered to have depression before the procedure, based on a diagnosis (55%), an antidepressant prescription (22%), or both (23%).

There were some differences at baseline between the two populations: Women with preoperative depression were more likely to have a comorbid pain disorder, compared with patients without depression (20% vs. 14%), another psychiatric disorder (2% vs. less than 1%), and a Charlson comorbidity (12% vs. 9%). They also were less likely to undergo a minimally invasive procedure than women without depression (66% vs. 79%). There was an increase in the prevalence of depression over time, from 16% to 23%.

Overall, 74% of women were prescribed an opioid during the perioperative period; 17% were filled before the hysterectomy was performed. Preoperative fills also increased over time, from 4% in 2001 to 21% in 2015.

Women with preoperative depression were at a slightly greater risk for perioperative opioid use (risk ratio, 1.08), but a greater risk for persistent postoperative opioid use (11% vs. 8%; RR, 1.43). The heightened risk for opioid use was similar whether the surgery was performed on an outpatient or inpatient basis.

The presence of other comorbidities in women with diagnosed depression or prescribed antidepressants complicates the findings, according to Dr. Carey. “There may be additional chronic pain factors that are confounding this data, but it is consistent with other data that de novo postoperative opioid dependence may be a higher risk for these patients, so it’s important for us to look at that critically.”

Dr. Carey has been a consultant for Teleflex Medical and a speaker for Med-IQ.

Immediate umbilical cord milking or delayed clamping of the umbilical cord had no significant impact on maternal outcomes, but infants were significantly more likely to experience severe intraventricular hemorrhage with umbilical cord milking, according to results of two studies published in JAMA.

arztsamui/Thinkstock

“While the evidence for neonatal benefit with delayed cord clamping at term is strong, data related to maternal outcomes, particularly after cesarean delivery, are largely lacking,” wrote Stephanie E. Purisch, MD, of Columbia University Irving Medical Center, New York, and colleagues.

In a randomized trial of 113 women who underwent cesarean deliveries of singleton infants, the researchers hypothesized that maternal blood loss would be greater with delayed cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995).

However, maternal blood loss, based on mean hemoglobin levels 1 day after delivery, was not significantly different between the delayed group (10.1 g/dL) and the immediate group (98 g/dL). The median time to cord clamping was 63 seconds in the delayed group and 6 seconds in the immediate group.

In addition, no significant differences occurred in 15 of 19 prespecified secondary outcomes. However, mean neonatal hemoglobin levels were significantly higher with delayed clamping, compared with levels associated with immediate clamping among 90 neonates for whom data were available (18.1 g/dL vs. 16.4 g/dL; P less than .001).

The results were limited by factors including lack of generalizability to other situations such as emergency or preterm deliveries and by the lack of a definition of a “clinically important postoperative hemoglobin change,” the researchers noted. However, the results show no significant impact of umbilical cord management on maternal hemoglobin in the study population.

In another study published in JAMA, Anup Katheria, MD, of Sharp Mary Birch Hospital for Women & Newborns, San Diego, and colleagues found no significant difference in rates of a composite outcome of death or severe intraventricular hemorrhage among infants randomized to umbilical cord milking (12%) vs. delayed umbilical cord clamping (8%). However, immediate umbilical cord milking was significantly associated with a higher rate of intraventricular hemorrhage alone, compared with delayed clamping (8% vs. 3%), and this signal of risk prompted the researchers to terminate the study earlier than intended.

The researchers randomized 474 infants born at less than 32 weeks’ gestation to umbilical cord milking or delayed umbilical cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004). The study was conducted at six sites in the United States and one site each in Ireland, Germany, and Canada between June 2017 and September 2018. “Because of the importance of long-term neurodevelopment, all surviving infants will be followed up to determine developmental outcomes at 22 to 26 months’ corrected gestational age,” they said.

The study was terminated early, which prevents definitive conclusions, the researchers noted, but a new study has been approved to compare umbilical cord milking with delayed umbilical cord clamping in infants of 30-32 weeks’ gestational age, they said.

“Although the safety of placental transfusion for the mother seems well established, it remains unclear which method of providing placental transfusion is best for the infant: delayed clamping and cutting the cord or milking the intact cord. The latter provides a transfusion more rapidly, which may facilitate initiation of resuscitation when needed,” Heike Rabe, MD, of the University of Sussex, Brighton, and Ola Andersson, PhD, of Lund (Sweden) University, wrote in an editorial accompanying the two studies (JAMA. 2019 Nov 19;322:1864-5. doi: 10.1001/jama.2019.16003).

The 8% incidence of severe intraventricular hemorrhage in the umbilical milking group in the study by Katheria and colleagues was higher than the 5.2% in a recent Cochrane review, but the 3% incidence of severe intraventricular hemorrhage in the delayed group was lower than the 4.5% in the Cochrane review, they said.

“Umbilical cord milking has been used in many hospitals without an increase in intraventricular hemorrhage being observed,” they noted.

“The study by Purisch et al. demonstrated the safety of delayed cord clamping for mothers delivering by cesarean at term,” the editorialists wrote. Studies are underway to identify the best techniques for cord clamping, they said.

“In the meantime, clinicians should follow the World Health Organization recommendation to delay cord clamping and cutting for 1 to 3 minutes for term infants and for at least 60 seconds for preterm infants to prevent iron deficiency and potentially enable more premature infants to survive,” they concluded.

Dr. Purisch received funding from the Maternal-Fetal Medicine Fellow Research Fund for the first study. Coauthor Cynthia Gyamfi-Bannerman, MD, reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Society for Maternal-Fetal Medicine/AMAG Pharmaceuticals, and personal fees from Sera Prognostics outside the submitted work. The second study was supported by NICHD in a grant to Dr. Katheria, who had no financial conflicts to disclose. Coauthor Gary Cutter, PhD, had numerous ties to pharmaceutical companies. The editorialists had no financial conflicts to disclose.

SOURCES: Purisch SE et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995; Katheria A et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004; Rabe H and Andersson O. JAMA. 2019 Nov 19; 322:1864-5.

Immediate umbilical cord milking or delayed clamping of the umbilical cord had no significant impact on maternal outcomes, but infants were significantly more likely to experience severe intraventricular hemorrhage with umbilical cord milking, according to results of two studies published in JAMA.

arztsamui/Thinkstock

“While the evidence for neonatal benefit with delayed cord clamping at term is strong, data related to maternal outcomes, particularly after cesarean delivery, are largely lacking,” wrote Stephanie E. Purisch, MD, of Columbia University Irving Medical Center, New York, and colleagues.

In a randomized trial of 113 women who underwent cesarean deliveries of singleton infants, the researchers hypothesized that maternal blood loss would be greater with delayed cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995).

However, maternal blood loss, based on mean hemoglobin levels 1 day after delivery, was not significantly different between the delayed group (10.1 g/dL) and the immediate group (98 g/dL). The median time to cord clamping was 63 seconds in the delayed group and 6 seconds in the immediate group.

In addition, no significant differences occurred in 15 of 19 prespecified secondary outcomes. However, mean neonatal hemoglobin levels were significantly higher with delayed clamping, compared with levels associated with immediate clamping among 90 neonates for whom data were available (18.1 g/dL vs. 16.4 g/dL; P less than .001).

The results were limited by factors including lack of generalizability to other situations such as emergency or preterm deliveries and by the lack of a definition of a “clinically important postoperative hemoglobin change,” the researchers noted. However, the results show no significant impact of umbilical cord management on maternal hemoglobin in the study population.

In another study published in JAMA, Anup Katheria, MD, of Sharp Mary Birch Hospital for Women & Newborns, San Diego, and colleagues found no significant difference in rates of a composite outcome of death or severe intraventricular hemorrhage among infants randomized to umbilical cord milking (12%) vs. delayed umbilical cord clamping (8%). However, immediate umbilical cord milking was significantly associated with a higher rate of intraventricular hemorrhage alone, compared with delayed clamping (8% vs. 3%), and this signal of risk prompted the researchers to terminate the study earlier than intended.

The researchers randomized 474 infants born at less than 32 weeks’ gestation to umbilical cord milking or delayed umbilical cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004). The study was conducted at six sites in the United States and one site each in Ireland, Germany, and Canada between June 2017 and September 2018. “Because of the importance of long-term neurodevelopment, all surviving infants will be followed up to determine developmental outcomes at 22 to 26 months’ corrected gestational age,” they said.

The study was terminated early, which prevents definitive conclusions, the researchers noted, but a new study has been approved to compare umbilical cord milking with delayed umbilical cord clamping in infants of 30-32 weeks’ gestational age, they said.

“Although the safety of placental transfusion for the mother seems well established, it remains unclear which method of providing placental transfusion is best for the infant: delayed clamping and cutting the cord or milking the intact cord. The latter provides a transfusion more rapidly, which may facilitate initiation of resuscitation when needed,” Heike Rabe, MD, of the University of Sussex, Brighton, and Ola Andersson, PhD, of Lund (Sweden) University, wrote in an editorial accompanying the two studies (JAMA. 2019 Nov 19;322:1864-5. doi: 10.1001/jama.2019.16003).

The 8% incidence of severe intraventricular hemorrhage in the umbilical milking group in the study by Katheria and colleagues was higher than the 5.2% in a recent Cochrane review, but the 3% incidence of severe intraventricular hemorrhage in the delayed group was lower than the 4.5% in the Cochrane review, they said.

“Umbilical cord milking has been used in many hospitals without an increase in intraventricular hemorrhage being observed,” they noted.

“The study by Purisch et al. demonstrated the safety of delayed cord clamping for mothers delivering by cesarean at term,” the editorialists wrote. Studies are underway to identify the best techniques for cord clamping, they said.

“In the meantime, clinicians should follow the World Health Organization recommendation to delay cord clamping and cutting for 1 to 3 minutes for term infants and for at least 60 seconds for preterm infants to prevent iron deficiency and potentially enable more premature infants to survive,” they concluded.

Dr. Purisch received funding from the Maternal-Fetal Medicine Fellow Research Fund for the first study. Coauthor Cynthia Gyamfi-Bannerman, MD, reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Society for Maternal-Fetal Medicine/AMAG Pharmaceuticals, and personal fees from Sera Prognostics outside the submitted work. The second study was supported by NICHD in a grant to Dr. Katheria, who had no financial conflicts to disclose. Coauthor Gary Cutter, PhD, had numerous ties to pharmaceutical companies. The editorialists had no financial conflicts to disclose.

SOURCES: Purisch SE et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995; Katheria A et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004; Rabe H and Andersson O. JAMA. 2019 Nov 19; 322:1864-5.

Immediate umbilical cord milking or delayed clamping of the umbilical cord had no significant impact on maternal outcomes, but infants were significantly more likely to experience severe intraventricular hemorrhage with umbilical cord milking, according to results of two studies published in JAMA.

arztsamui/Thinkstock

“While the evidence for neonatal benefit with delayed cord clamping at term is strong, data related to maternal outcomes, particularly after cesarean delivery, are largely lacking,” wrote Stephanie E. Purisch, MD, of Columbia University Irving Medical Center, New York, and colleagues.

In a randomized trial of 113 women who underwent cesarean deliveries of singleton infants, the researchers hypothesized that maternal blood loss would be greater with delayed cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995).

However, maternal blood loss, based on mean hemoglobin levels 1 day after delivery, was not significantly different between the delayed group (10.1 g/dL) and the immediate group (98 g/dL). The median time to cord clamping was 63 seconds in the delayed group and 6 seconds in the immediate group.

In addition, no significant differences occurred in 15 of 19 prespecified secondary outcomes. However, mean neonatal hemoglobin levels were significantly higher with delayed clamping, compared with levels associated with immediate clamping among 90 neonates for whom data were available (18.1 g/dL vs. 16.4 g/dL; P less than .001).

The results were limited by factors including lack of generalizability to other situations such as emergency or preterm deliveries and by the lack of a definition of a “clinically important postoperative hemoglobin change,” the researchers noted. However, the results show no significant impact of umbilical cord management on maternal hemoglobin in the study population.

In another study published in JAMA, Anup Katheria, MD, of Sharp Mary Birch Hospital for Women & Newborns, San Diego, and colleagues found no significant difference in rates of a composite outcome of death or severe intraventricular hemorrhage among infants randomized to umbilical cord milking (12%) vs. delayed umbilical cord clamping (8%). However, immediate umbilical cord milking was significantly associated with a higher rate of intraventricular hemorrhage alone, compared with delayed clamping (8% vs. 3%), and this signal of risk prompted the researchers to terminate the study earlier than intended.

The researchers randomized 474 infants born at less than 32 weeks’ gestation to umbilical cord milking or delayed umbilical cord clamping (JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004). The study was conducted at six sites in the United States and one site each in Ireland, Germany, and Canada between June 2017 and September 2018. “Because of the importance of long-term neurodevelopment, all surviving infants will be followed up to determine developmental outcomes at 22 to 26 months’ corrected gestational age,” they said.

The study was terminated early, which prevents definitive conclusions, the researchers noted, but a new study has been approved to compare umbilical cord milking with delayed umbilical cord clamping in infants of 30-32 weeks’ gestational age, they said.

“Although the safety of placental transfusion for the mother seems well established, it remains unclear which method of providing placental transfusion is best for the infant: delayed clamping and cutting the cord or milking the intact cord. The latter provides a transfusion more rapidly, which may facilitate initiation of resuscitation when needed,” Heike Rabe, MD, of the University of Sussex, Brighton, and Ola Andersson, PhD, of Lund (Sweden) University, wrote in an editorial accompanying the two studies (JAMA. 2019 Nov 19;322:1864-5. doi: 10.1001/jama.2019.16003).

The 8% incidence of severe intraventricular hemorrhage in the umbilical milking group in the study by Katheria and colleagues was higher than the 5.2% in a recent Cochrane review, but the 3% incidence of severe intraventricular hemorrhage in the delayed group was lower than the 4.5% in the Cochrane review, they said.

“Umbilical cord milking has been used in many hospitals without an increase in intraventricular hemorrhage being observed,” they noted.

“The study by Purisch et al. demonstrated the safety of delayed cord clamping for mothers delivering by cesarean at term,” the editorialists wrote. Studies are underway to identify the best techniques for cord clamping, they said.

“In the meantime, clinicians should follow the World Health Organization recommendation to delay cord clamping and cutting for 1 to 3 minutes for term infants and for at least 60 seconds for preterm infants to prevent iron deficiency and potentially enable more premature infants to survive,” they concluded.

Dr. Purisch received funding from the Maternal-Fetal Medicine Fellow Research Fund for the first study. Coauthor Cynthia Gyamfi-Bannerman, MD, reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Society for Maternal-Fetal Medicine/AMAG Pharmaceuticals, and personal fees from Sera Prognostics outside the submitted work. The second study was supported by NICHD in a grant to Dr. Katheria, who had no financial conflicts to disclose. Coauthor Gary Cutter, PhD, had numerous ties to pharmaceutical companies. The editorialists had no financial conflicts to disclose.

SOURCES: Purisch SE et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.15995; Katheria A et al. JAMA. 2019 Nov 19. doi: 10.1001/jama.2019.16004; Rabe H and Andersson O. JAMA. 2019 Nov 19; 322:1864-5.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

Secondary surgical cytoreduction was feasible but did not extend overall survival among women with platinum-sensitive, recurrent ovarian cancer in a prospective, randomized, phase 3 clinical trial, investigators report.

Women who received platinum-based chemotherapy plus surgery had a median overall survival of about 51 months, compared with 64.7 months for women who received platinum-based chemotherapy and no surgery, according to the results of the Gynecologic Oncology Group (GOG)-0213 study, a multicenter, open-label, randomized, phase 3 trial.

These findings “call into question” the merits of surgical cytoreduction, said the authors, led by Robert L. Coleman, MD, of the department of gynecologic oncology and reproductive medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Specifically, the shorter overall survival in the surgery group vs. no-surgery group emphasizes the “importance of formally assessing the value of the procedure in clinical care,” said Dr. Coleman and coauthors in the report on GOG-0213. The study was published in the New England Journal of Medicine.

Clinical practice guidelines from the National Comprehensive Cancer Network currently cite secondary cytoreduction as an option for treatment of patients who experience a treatment-free interval of at least 6 months after a complete remission achieved on prior chemotherapy, the GOG-0213 investigators wrote.

Beyond GOG-0213, there are several other randomized trials underway in this setting, including DESKTOP III, a multicenter study comparing the efficacy of chemotherapy alone to chemotherapy plus additional tumor debulking surgery in women with recurrent platinum-sensitive ovarian cancer.

“Maturity of the DESKTOP III trial and other trials will shape the debate on the value or merit of surgery in this patient population,” wrote Dr. Coleman and colleagues.

The GOG-0213 study, conducted in 67 centers, 65 of which were in the United States, had both a chemotherapy objective and a surgical objective in patients with platinum-sensitive recurrent ovarian cancer, investigators said.

Results of the chemotherapy objective, published in 2017 in Lancet Oncology, indicated that bevacizumab added to standard chemotherapy, followed by maintenance bevacizumab until progression, improved median overall survival.

The more recently reported results focused on 485 women of who 245 were randomized to receive chemotherapy alone. While 240 were randomized to receive cytoreduction prior to chemotherapy, 15 declined surgery, leaving 225 eligible patients (94%).

The adjusted hazard ratio for death was 1.29 (95% confidence interval, 0.97-1.72; P = 0.08) for surgery, compared with no surgery, which translated into median overall survival times of 50.6 months in the surgery arm and 64.7 months in the no-surgery arm, Dr. Coleman and coauthors reported.

However, 30-day morbidity and mortality were low, at 9% (20 patients) and 0.4% (1 patient), and just 4% of cases (8 patients) were aborted, they added.

Quality of life significantly declined right after secondary cytoreduction, although after recovery no significant differences were found between groups, according to the investigators.

Taken together, those findings “did not indicate that surgery plus chemotherapy was superior to chemotherapy alone,” investigators concluded.

However, several factors in GOG-0213, including longer-than-expected survival times and substantial platinum sensitivity among women in the trial, could have diluted an independent surgical effect, they said.

Dr. Coleman reported disclosures related to several pharmaceutical companies, including Agenus, AstraZeneca, Clovis, GamaMabs, Genmab, Janssen, Medivation, Merck, Regeneron, Roche/Genentech, OncoQuest, and Tesaro.

SOURCE: Coleman RL et al. N Engl J Med. 2019;381:1929-39.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

PHILADELPHIA – Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

A 47-year-old woman was referred to the gynecology office by her primary care NP for surgical excision of an enlarging nodule on the right side of her mons pubis. Onset occurred about 6 months earlier. The patient reported that symptoms waxed and waned but had worsened progressively over the past 2 to 3 months, adding that the nodule hurt only occasionally. She noted that symptoms were exacerbated by exercise, specifically running. Further questioning prompted the observation that her symptoms were more noticeable at the time of menses.

The patient’s medical history was unremarkable, with no chronic conditions; her surgical history consisted of a wisdom tooth extraction. She had no known drug allergies. Her family history included cerebrovascular accident, hypertension, and arthritis. Reproductive history revealed that she was G1 P1, with a 38-week uncomplicated vaginal delivery. She experienced menarche at age 14, and her menses was regular at every 28 days. For the past 5 days, there had been no dysmenorrhea. The patient was married, exercised regularly, and did not use tobacco, alcohol, or illicit drugs.

On examination, the patient’s blood pressure was 123/73 mm Hg; heart rate, 77 beats/min; respiratory rate, 12 breaths/min; weight, 128 lb; height, 5 ft 7 in; O₂ saturation, 99% on room air; and BMI, 20. The patient was alert and oriented to person, place, and time. She was thin, appeared physically fit, and exhibited no signs of distress. Her physical exam was unremarkable, apart from a firm, minimally tender, well-circumscribed, 3.5 × 3.5–cm nodule right of midline on the mons pubis.

The patient was scheduled for outpatient surgical excision of a benign skin lesion (excluding skin tags) of the genitalia, 3.1 to 3.5 cm (CPT code 11424). During this procedure, it became evident that this was not a lipoma. The lesion was exceptionally hard, and it was difficult to discern if it was incorporated into the rectus abdominis near the point of attachment to the pubic symphysis. The lesion was unintentionally disrupted, revealing black powdery material within the capsule. The tissue was sent for a fast, frozen section that showed “soft tissue with extensive involvement by endometriosis.” The pathology report noted “[m]any endometrial glands in a background of stromal tissue. Necrosis was not a feature. No evidence of atypia.” The patient’s postoperative diagnosis was endometriosis.

DISCUSSION

Endometriosis occurs when endometrial or “endometrial-like” tissue is displaced to sites other than within the uterus. It is most frequently found on tissues close to the uterus, such as the ovaries or pelvic peritoneum. Estrogen is the driving force that feeds the endometrium, causing it to proliferate, whether inside or outside the uterus. Given this dependence on hormones, endometriosis occurs most often during a woman’s fertile years, although it can occur after menopause. Endometriosis is common, affecting at least 10% of premenopausal women; moreover, it is identified as the cause in 70% of all female chronic pelvic pain cases.^1-4

Endometriosis has certain identifiable features, such as chronic pain, dyspareunia, infertility, and menstrual and gastrointestinal symptoms. However, it is seldom diagnosed quickly; studies indicate that diagnosis can be delayed by 5 to 10 years after a patient has first sought treatment for symptoms.^2,4 Multiple factors contribute to a lag in diagnosis: Presentation is not always straightforward. There are no definitive lab values or biomarkers. Symptoms vary from patient to patient, as do clinical skills from one diagnostician to another.¹

Unlike pelvic endometriosis, inguinal endometriosis is not common; disease in this location encompasses only 0.3% to 0.6% of all diagnosed cases.^3,5-7 Since the discovery of the first known case of round ligament endometriosis in 1896, there have been only 70 cases reported in the medical literature.^6,7

If the more common form of endometriosis is frequently missed, this rarely seen variant presents an even greater diagnostic challenge. The typical presentation of inguinal endometriosis includes a firm nodule in the groin, accompanied by tenderness and swelling. A careful history will allude to pain that occurs cyclically with menses.

Cause

Among several theories about the etiology of endometriosis, the most popular has been retrograde menstruation.^1,4,5 According to this hypothesis, the flow of menstrual blood moves backward through the fallopian tubes, spilling into the pelvic cavity and carrying endometrial tissue with it. One theory purports that endometrial tissue is transplanted from the uterus to other areas of the body via the bloodstream or the lymphatics, much like a metastatic disease.^1,4 Another theory states that cells outside the uterus, which line the peritoneum, transform into endometrial cells through metaplasia.^4,5 Endometrial tissue can also be transplanted iatrogenically during surgery—for example, when endometrial tissue is displaced during a cesarean delivery, resulting in implants above the fascia and below the subcutaneous layers. Several other hypotheses concern stem-cell involvement, hormonal factors, immune system dysfunction, and genetics.^4,5 Currently, there are no definitive answers.

Location

During maturation, the parietal peritoneum develops a pouch called the processus vaginalis, which serves as a passageway for the gubernaculum to transport the round ligament running from the uterus, through the inguinal canal, and ending at the labia. After these structures reach their destination, in normal development, the processus vaginalis degenerates, closing the inguinal canal. Occasionally the processus vaginalis fails to close, allowing for a communication pathway between the peritoneal cavity and the inguinal canal. This leaves the canal vulnerable to the contents of the pelvic cavity, such as a hernia or hydrocele, and provides a clear path for endometriosis.^5-7 The implant found in the case patient was at the point where the external ring lies, just above the right pubic tubercle (see Figure 1).

Endometriosis implants can occur anywhere along the round ligament in either the intrapelvic or extrapelvic segments. Implants have also been found in the wall of a hernia sac, the wall of a Nuck canal hydrocele, or even in the subcutaneous tissue surrounding the inguinal canal.³ Interestingly, inguinal endometriosis occurs more often in the right side (up to 94% of cases) than in the left side, as was the case with our patient.^5-7 The reason for this predominance has not been established, although there are several theories, including one that suggests the left side is afforded protection by the sigmoid colon.^5-7

Laboratory diagnosis

Imaging, such as ultrasound and MRI, offers some diagnostic benefit, although its usefulness is most often realized in the pelvis. Pelvic ultrasound can be used to identify ovarian endometriomas.¹ MRI can help rule out, locate, or sometimes determine the degree of deep infiltrating endometriosis, which is an indispensable tool for surgical planning.^5,7 Unfortunately, the diagnostic accuracy for extra-pelvic lesions is variable; neither modality is particularly useful in identifying superficial lesions, which comprises most cases.

Ultrasound of the groin can be employed to evaluate for hernia; if a hernia has been excluded, histologic confirmation can be obtained via fine-needle aspiration of nodule contents.^5,7 One caveat is that these tests are helpful only if the clinician suspects the diagnosis and orders them. The definitive diagnostic test remains direct visualization, which requires laparoscopy.^1,5

Differential diagnosis

Lipoma was a favored diagnosis in this case because of the palpable, well-circumscribed borders, nontender on exam; intermittent, minimal tenderness; and no evidence of erythema or color change. A second possibility was an enlarged lymph node, which was less likely due to the location, large size, and sudden onset without any accompanying symptoms of infection or chronic illness. Finally, an inguinal hernia was least likely, again because of well-defined borders, no history of a lump in the area, a nodule that was not reducible, only minimal tenderness, and no color changes on the skin.

Management

Definitive treatment for inguinal endometriosis entails complete surgical excision.^5-7 The provider should be prepared to repair a defect after the excision; there is potential for a substantial defect that might require mesh. Additionally, a herniorrhaphy may be indicated if there is a coexisting hernia.⁵ The risk for recurrent disease in the inguinal canal after treatment is uncommon, unless the excision was not complete.³

There is an association between inguinal and pelvic endometriosis but not a direct correlation. Data on concomitant pelvic and inguinal endometriosis have been variable. In one case series of 9 patients diagnosed with inguinal endometriosis, none had a history of pelvic endometriosis, and only 1 was subsequently diagnosed with pelvic endometriosis.⁷ An increased association was noted for patients with implants found on the proximal segment of the round ligament.⁷ However, implants on the extrapelvic segment were not likely to represent pelvic disease but rather isolated lesions in the canal.⁷ For those with pelvic endometriosis, complications and recurrence are likely, resulting in the need for long-term treatment.

There is some debate in the literature whether to proceed with laparoscopy once inguinal endometriosis has been identified. Diagnostic laparoscopy to evaluate the pelvis is indicated for symptomatic patients or for cases in which an indirect inguinal hernia is suspected.⁵ Laparoscopy can offer the benefit of both a diagnostic tool and a mechanism for treatment. However, this is an invasive procedure that also incurs risks. The medical provider, in discussion with the patient, must weigh the risks against the benefits of an invasive procedure before determining how to proceed.

 

 

OUTCOME FOR THE CASE PATIENT

The lesion was excised completely. Since the patient had been entirely asymptomatic until age 47, and the risks of a potentially unnecessary surgery outweighed the theoretical benefits, the decision was made not to perform a diagnostic laparoscopy to investigate for pelvic endometriosis. The patient made a complete and uneventful recovery. No further treatment was initiated. She continues to be asymptomatic, denying any menstrual complaints, dyspareunia, or further problems with the groin.

CONCLUSION

This case describes a satellite lesion of endometrial tissue found in an unusual location, in a patient with no history, no risk factors, and no symptoms. The final diagnosis had been omitted from the differential—perhaps because the patient initially associated her symptoms with exercise and mentioned the correlation to her menstrual cycle as an afterthought. Fortunately, the correct diagnosis was made and the appropriate treatment provided.

There are numerous presentations of endometriosis; extrapelvic lesions can have very different, often vague, presentations when compared to the familiar symptoms of pelvic disease. Unfortunately, diagnosis is often delayed. Obscure presentations, in unusual sites, can further impede both speed and accuracy of diagnosis. To date, there are no lab tests or biomarkers to aid diagnosis; imaging studies are inconsistent. Until more accurate diagnostic tools become available, the diagnosis remains dependent on history taking, physical exam, and the clinical judgment of the provider. The astute clinician will recognize the catamenial pattern and consider endometriosis as part of the differential.

A 47-year-old woman was referred to the gynecology office by her primary care NP for surgical excision of an enlarging nodule on the right side of her mons pubis. Onset occurred about 6 months earlier. The patient reported that symptoms waxed and waned but had worsened progressively over the past 2 to 3 months, adding that the nodule hurt only occasionally. She noted that symptoms were exacerbated by exercise, specifically running. Further questioning prompted the observation that her symptoms were more noticeable at the time of menses.

The patient’s medical history was unremarkable, with no chronic conditions; her surgical history consisted of a wisdom tooth extraction. She had no known drug allergies. Her family history included cerebrovascular accident, hypertension, and arthritis. Reproductive history revealed that she was G1 P1, with a 38-week uncomplicated vaginal delivery. She experienced menarche at age 14, and her menses was regular at every 28 days. For the past 5 days, there had been no dysmenorrhea. The patient was married, exercised regularly, and did not use tobacco, alcohol, or illicit drugs.

On examination, the patient’s blood pressure was 123/73 mm Hg; heart rate, 77 beats/min; respiratory rate, 12 breaths/min; weight, 128 lb; height, 5 ft 7 in; O₂ saturation, 99% on room air; and BMI, 20. The patient was alert and oriented to person, place, and time. She was thin, appeared physically fit, and exhibited no signs of distress. Her physical exam was unremarkable, apart from a firm, minimally tender, well-circumscribed, 3.5 × 3.5–cm nodule right of midline on the mons pubis.

The patient was scheduled for outpatient surgical excision of a benign skin lesion (excluding skin tags) of the genitalia, 3.1 to 3.5 cm (CPT code 11424). During this procedure, it became evident that this was not a lipoma. The lesion was exceptionally hard, and it was difficult to discern if it was incorporated into the rectus abdominis near the point of attachment to the pubic symphysis. The lesion was unintentionally disrupted, revealing black powdery material within the capsule. The tissue was sent for a fast, frozen section that showed “soft tissue with extensive involvement by endometriosis.” The pathology report noted “[m]any endometrial glands in a background of stromal tissue. Necrosis was not a feature. No evidence of atypia.” The patient’s postoperative diagnosis was endometriosis.

DISCUSSION

Endometriosis occurs when endometrial or “endometrial-like” tissue is displaced to sites other than within the uterus. It is most frequently found on tissues close to the uterus, such as the ovaries or pelvic peritoneum. Estrogen is the driving force that feeds the endometrium, causing it to proliferate, whether inside or outside the uterus. Given this dependence on hormones, endometriosis occurs most often during a woman’s fertile years, although it can occur after menopause. Endometriosis is common, affecting at least 10% of premenopausal women; moreover, it is identified as the cause in 70% of all female chronic pelvic pain cases.^1-4

Endometriosis has certain identifiable features, such as chronic pain, dyspareunia, infertility, and menstrual and gastrointestinal symptoms. However, it is seldom diagnosed quickly; studies indicate that diagnosis can be delayed by 5 to 10 years after a patient has first sought treatment for symptoms.^2,4 Multiple factors contribute to a lag in diagnosis: Presentation is not always straightforward. There are no definitive lab values or biomarkers. Symptoms vary from patient to patient, as do clinical skills from one diagnostician to another.¹

Unlike pelvic endometriosis, inguinal endometriosis is not common; disease in this location encompasses only 0.3% to 0.6% of all diagnosed cases.^3,5-7 Since the discovery of the first known case of round ligament endometriosis in 1896, there have been only 70 cases reported in the medical literature.^6,7

If the more common form of endometriosis is frequently missed, this rarely seen variant presents an even greater diagnostic challenge. The typical presentation of inguinal endometriosis includes a firm nodule in the groin, accompanied by tenderness and swelling. A careful history will allude to pain that occurs cyclically with menses.

Cause

Among several theories about the etiology of endometriosis, the most popular has been retrograde menstruation.^1,4,5 According to this hypothesis, the flow of menstrual blood moves backward through the fallopian tubes, spilling into the pelvic cavity and carrying endometrial tissue with it. One theory purports that endometrial tissue is transplanted from the uterus to other areas of the body via the bloodstream or the lymphatics, much like a metastatic disease.^1,4 Another theory states that cells outside the uterus, which line the peritoneum, transform into endometrial cells through metaplasia.^4,5 Endometrial tissue can also be transplanted iatrogenically during surgery—for example, when endometrial tissue is displaced during a cesarean delivery, resulting in implants above the fascia and below the subcutaneous layers. Several other hypotheses concern stem-cell involvement, hormonal factors, immune system dysfunction, and genetics.^4,5 Currently, there are no definitive answers.

Location

During maturation, the parietal peritoneum develops a pouch called the processus vaginalis, which serves as a passageway for the gubernaculum to transport the round ligament running from the uterus, through the inguinal canal, and ending at the labia. After these structures reach their destination, in normal development, the processus vaginalis degenerates, closing the inguinal canal. Occasionally the processus vaginalis fails to close, allowing for a communication pathway between the peritoneal cavity and the inguinal canal. This leaves the canal vulnerable to the contents of the pelvic cavity, such as a hernia or hydrocele, and provides a clear path for endometriosis.^5-7 The implant found in the case patient was at the point where the external ring lies, just above the right pubic tubercle (see Figure 1).

Endometriosis implants can occur anywhere along the round ligament in either the intrapelvic or extrapelvic segments. Implants have also been found in the wall of a hernia sac, the wall of a Nuck canal hydrocele, or even in the subcutaneous tissue surrounding the inguinal canal.³ Interestingly, inguinal endometriosis occurs more often in the right side (up to 94% of cases) than in the left side, as was the case with our patient.^5-7 The reason for this predominance has not been established, although there are several theories, including one that suggests the left side is afforded protection by the sigmoid colon.^5-7

Laboratory diagnosis

Imaging, such as ultrasound and MRI, offers some diagnostic benefit, although its usefulness is most often realized in the pelvis. Pelvic ultrasound can be used to identify ovarian endometriomas.¹ MRI can help rule out, locate, or sometimes determine the degree of deep infiltrating endometriosis, which is an indispensable tool for surgical planning.^5,7 Unfortunately, the diagnostic accuracy for extra-pelvic lesions is variable; neither modality is particularly useful in identifying superficial lesions, which comprises most cases.

Ultrasound of the groin can be employed to evaluate for hernia; if a hernia has been excluded, histologic confirmation can be obtained via fine-needle aspiration of nodule contents.^5,7 One caveat is that these tests are helpful only if the clinician suspects the diagnosis and orders them. The definitive diagnostic test remains direct visualization, which requires laparoscopy.^1,5

Differential diagnosis

Lipoma was a favored diagnosis in this case because of the palpable, well-circumscribed borders, nontender on exam; intermittent, minimal tenderness; and no evidence of erythema or color change. A second possibility was an enlarged lymph node, which was less likely due to the location, large size, and sudden onset without any accompanying symptoms of infection or chronic illness. Finally, an inguinal hernia was least likely, again because of well-defined borders, no history of a lump in the area, a nodule that was not reducible, only minimal tenderness, and no color changes on the skin.

Management

Definitive treatment for inguinal endometriosis entails complete surgical excision.^5-7 The provider should be prepared to repair a defect after the excision; there is potential for a substantial defect that might require mesh. Additionally, a herniorrhaphy may be indicated if there is a coexisting hernia.⁵ The risk for recurrent disease in the inguinal canal after treatment is uncommon, unless the excision was not complete.³

There is an association between inguinal and pelvic endometriosis but not a direct correlation. Data on concomitant pelvic and inguinal endometriosis have been variable. In one case series of 9 patients diagnosed with inguinal endometriosis, none had a history of pelvic endometriosis, and only 1 was subsequently diagnosed with pelvic endometriosis.⁷ An increased association was noted for patients with implants found on the proximal segment of the round ligament.⁷ However, implants on the extrapelvic segment were not likely to represent pelvic disease but rather isolated lesions in the canal.⁷ For those with pelvic endometriosis, complications and recurrence are likely, resulting in the need for long-term treatment.

There is some debate in the literature whether to proceed with laparoscopy once inguinal endometriosis has been identified. Diagnostic laparoscopy to evaluate the pelvis is indicated for symptomatic patients or for cases in which an indirect inguinal hernia is suspected.⁵ Laparoscopy can offer the benefit of both a diagnostic tool and a mechanism for treatment. However, this is an invasive procedure that also incurs risks. The medical provider, in discussion with the patient, must weigh the risks against the benefits of an invasive procedure before determining how to proceed.

 

 

OUTCOME FOR THE CASE PATIENT

The lesion was excised completely. Since the patient had been entirely asymptomatic until age 47, and the risks of a potentially unnecessary surgery outweighed the theoretical benefits, the decision was made not to perform a diagnostic laparoscopy to investigate for pelvic endometriosis. The patient made a complete and uneventful recovery. No further treatment was initiated. She continues to be asymptomatic, denying any menstrual complaints, dyspareunia, or further problems with the groin.

CONCLUSION

This case describes a satellite lesion of endometrial tissue found in an unusual location, in a patient with no history, no risk factors, and no symptoms. The final diagnosis had been omitted from the differential—perhaps because the patient initially associated her symptoms with exercise and mentioned the correlation to her menstrual cycle as an afterthought. Fortunately, the correct diagnosis was made and the appropriate treatment provided.

There are numerous presentations of endometriosis; extrapelvic lesions can have very different, often vague, presentations when compared to the familiar symptoms of pelvic disease. Unfortunately, diagnosis is often delayed. Obscure presentations, in unusual sites, can further impede both speed and accuracy of diagnosis. To date, there are no lab tests or biomarkers to aid diagnosis; imaging studies are inconsistent. Until more accurate diagnostic tools become available, the diagnosis remains dependent on history taking, physical exam, and the clinical judgment of the provider. The astute clinician will recognize the catamenial pattern and consider endometriosis as part of the differential.

A 47-year-old woman was referred to the gynecology office by her primary care NP for surgical excision of an enlarging nodule on the right side of her mons pubis. Onset occurred about 6 months earlier. The patient reported that symptoms waxed and waned but had worsened progressively over the past 2 to 3 months, adding that the nodule hurt only occasionally. She noted that symptoms were exacerbated by exercise, specifically running. Further questioning prompted the observation that her symptoms were more noticeable at the time of menses.

The patient’s medical history was unremarkable, with no chronic conditions; her surgical history consisted of a wisdom tooth extraction. She had no known drug allergies. Her family history included cerebrovascular accident, hypertension, and arthritis. Reproductive history revealed that she was G1 P1, with a 38-week uncomplicated vaginal delivery. She experienced menarche at age 14, and her menses was regular at every 28 days. For the past 5 days, there had been no dysmenorrhea. The patient was married, exercised regularly, and did not use tobacco, alcohol, or illicit drugs.

On examination, the patient’s blood pressure was 123/73 mm Hg; heart rate, 77 beats/min; respiratory rate, 12 breaths/min; weight, 128 lb; height, 5 ft 7 in; O₂ saturation, 99% on room air; and BMI, 20. The patient was alert and oriented to person, place, and time. She was thin, appeared physically fit, and exhibited no signs of distress. Her physical exam was unremarkable, apart from a firm, minimally tender, well-circumscribed, 3.5 × 3.5–cm nodule right of midline on the mons pubis.

The patient was scheduled for outpatient surgical excision of a benign skin lesion (excluding skin tags) of the genitalia, 3.1 to 3.5 cm (CPT code 11424). During this procedure, it became evident that this was not a lipoma. The lesion was exceptionally hard, and it was difficult to discern if it was incorporated into the rectus abdominis near the point of attachment to the pubic symphysis. The lesion was unintentionally disrupted, revealing black powdery material within the capsule. The tissue was sent for a fast, frozen section that showed “soft tissue with extensive involvement by endometriosis.” The pathology report noted “[m]any endometrial glands in a background of stromal tissue. Necrosis was not a feature. No evidence of atypia.” The patient’s postoperative diagnosis was endometriosis.

DISCUSSION

Endometriosis occurs when endometrial or “endometrial-like” tissue is displaced to sites other than within the uterus. It is most frequently found on tissues close to the uterus, such as the ovaries or pelvic peritoneum. Estrogen is the driving force that feeds the endometrium, causing it to proliferate, whether inside or outside the uterus. Given this dependence on hormones, endometriosis occurs most often during a woman’s fertile years, although it can occur after menopause. Endometriosis is common, affecting at least 10% of premenopausal women; moreover, it is identified as the cause in 70% of all female chronic pelvic pain cases.^1-4

Endometriosis has certain identifiable features, such as chronic pain, dyspareunia, infertility, and menstrual and gastrointestinal symptoms. However, it is seldom diagnosed quickly; studies indicate that diagnosis can be delayed by 5 to 10 years after a patient has first sought treatment for symptoms.^2,4 Multiple factors contribute to a lag in diagnosis: Presentation is not always straightforward. There are no definitive lab values or biomarkers. Symptoms vary from patient to patient, as do clinical skills from one diagnostician to another.¹

Unlike pelvic endometriosis, inguinal endometriosis is not common; disease in this location encompasses only 0.3% to 0.6% of all diagnosed cases.^3,5-7 Since the discovery of the first known case of round ligament endometriosis in 1896, there have been only 70 cases reported in the medical literature.^6,7

If the more common form of endometriosis is frequently missed, this rarely seen variant presents an even greater diagnostic challenge. The typical presentation of inguinal endometriosis includes a firm nodule in the groin, accompanied by tenderness and swelling. A careful history will allude to pain that occurs cyclically with menses.

Cause

Among several theories about the etiology of endometriosis, the most popular has been retrograde menstruation.^1,4,5 According to this hypothesis, the flow of menstrual blood moves backward through the fallopian tubes, spilling into the pelvic cavity and carrying endometrial tissue with it. One theory purports that endometrial tissue is transplanted from the uterus to other areas of the body via the bloodstream or the lymphatics, much like a metastatic disease.^1,4 Another theory states that cells outside the uterus, which line the peritoneum, transform into endometrial cells through metaplasia.^4,5 Endometrial tissue can also be transplanted iatrogenically during surgery—for example, when endometrial tissue is displaced during a cesarean delivery, resulting in implants above the fascia and below the subcutaneous layers. Several other hypotheses concern stem-cell involvement, hormonal factors, immune system dysfunction, and genetics.^4,5 Currently, there are no definitive answers.

Location

During maturation, the parietal peritoneum develops a pouch called the processus vaginalis, which serves as a passageway for the gubernaculum to transport the round ligament running from the uterus, through the inguinal canal, and ending at the labia. After these structures reach their destination, in normal development, the processus vaginalis degenerates, closing the inguinal canal. Occasionally the processus vaginalis fails to close, allowing for a communication pathway between the peritoneal cavity and the inguinal canal. This leaves the canal vulnerable to the contents of the pelvic cavity, such as a hernia or hydrocele, and provides a clear path for endometriosis.^5-7 The implant found in the case patient was at the point where the external ring lies, just above the right pubic tubercle (see Figure 1).

Endometriosis implants can occur anywhere along the round ligament in either the intrapelvic or extrapelvic segments. Implants have also been found in the wall of a hernia sac, the wall of a Nuck canal hydrocele, or even in the subcutaneous tissue surrounding the inguinal canal.³ Interestingly, inguinal endometriosis occurs more often in the right side (up to 94% of cases) than in the left side, as was the case with our patient.^5-7 The reason for this predominance has not been established, although there are several theories, including one that suggests the left side is afforded protection by the sigmoid colon.^5-7

Laboratory diagnosis

Imaging, such as ultrasound and MRI, offers some diagnostic benefit, although its usefulness is most often realized in the pelvis. Pelvic ultrasound can be used to identify ovarian endometriomas.¹ MRI can help rule out, locate, or sometimes determine the degree of deep infiltrating endometriosis, which is an indispensable tool for surgical planning.^5,7 Unfortunately, the diagnostic accuracy for extra-pelvic lesions is variable; neither modality is particularly useful in identifying superficial lesions, which comprises most cases.

Ultrasound of the groin can be employed to evaluate for hernia; if a hernia has been excluded, histologic confirmation can be obtained via fine-needle aspiration of nodule contents.^5,7 One caveat is that these tests are helpful only if the clinician suspects the diagnosis and orders them. The definitive diagnostic test remains direct visualization, which requires laparoscopy.^1,5

Differential diagnosis

Lipoma was a favored diagnosis in this case because of the palpable, well-circumscribed borders, nontender on exam; intermittent, minimal tenderness; and no evidence of erythema or color change. A second possibility was an enlarged lymph node, which was less likely due to the location, large size, and sudden onset without any accompanying symptoms of infection or chronic illness. Finally, an inguinal hernia was least likely, again because of well-defined borders, no history of a lump in the area, a nodule that was not reducible, only minimal tenderness, and no color changes on the skin.

Management

Definitive treatment for inguinal endometriosis entails complete surgical excision.^5-7 The provider should be prepared to repair a defect after the excision; there is potential for a substantial defect that might require mesh. Additionally, a herniorrhaphy may be indicated if there is a coexisting hernia.⁵ The risk for recurrent disease in the inguinal canal after treatment is uncommon, unless the excision was not complete.³

There is an association between inguinal and pelvic endometriosis but not a direct correlation. Data on concomitant pelvic and inguinal endometriosis have been variable. In one case series of 9 patients diagnosed with inguinal endometriosis, none had a history of pelvic endometriosis, and only 1 was subsequently diagnosed with pelvic endometriosis.⁷ An increased association was noted for patients with implants found on the proximal segment of the round ligament.⁷ However, implants on the extrapelvic segment were not likely to represent pelvic disease but rather isolated lesions in the canal.⁷ For those with pelvic endometriosis, complications and recurrence are likely, resulting in the need for long-term treatment.

There is some debate in the literature whether to proceed with laparoscopy once inguinal endometriosis has been identified. Diagnostic laparoscopy to evaluate the pelvis is indicated for symptomatic patients or for cases in which an indirect inguinal hernia is suspected.⁵ Laparoscopy can offer the benefit of both a diagnostic tool and a mechanism for treatment. However, this is an invasive procedure that also incurs risks. The medical provider, in discussion with the patient, must weigh the risks against the benefits of an invasive procedure before determining how to proceed.

 

 

OUTCOME FOR THE CASE PATIENT

The lesion was excised completely. Since the patient had been entirely asymptomatic until age 47, and the risks of a potentially unnecessary surgery outweighed the theoretical benefits, the decision was made not to perform a diagnostic laparoscopy to investigate for pelvic endometriosis. The patient made a complete and uneventful recovery. No further treatment was initiated. She continues to be asymptomatic, denying any menstrual complaints, dyspareunia, or further problems with the groin.

CONCLUSION

This case describes a satellite lesion of endometrial tissue found in an unusual location, in a patient with no history, no risk factors, and no symptoms. The final diagnosis had been omitted from the differential—perhaps because the patient initially associated her symptoms with exercise and mentioned the correlation to her menstrual cycle as an afterthought. Fortunately, the correct diagnosis was made and the appropriate treatment provided.

There are numerous presentations of endometriosis; extrapelvic lesions can have very different, often vague, presentations when compared to the familiar symptoms of pelvic disease. Unfortunately, diagnosis is often delayed. Obscure presentations, in unusual sites, can further impede both speed and accuracy of diagnosis. To date, there are no lab tests or biomarkers to aid diagnosis; imaging studies are inconsistent. Until more accurate diagnostic tools become available, the diagnosis remains dependent on history taking, physical exam, and the clinical judgment of the provider. The astute clinician will recognize the catamenial pattern and consider endometriosis as part of the differential.

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

The Food and Drug Administration announced that it has approved cefiderocol (Fetroja), an IV antibacterial drug to treat complicated urinary tract infections (cUTIs), including kidney infections, caused by multidrug-resistant gram-negative microorganisms in patients 18 years of age or older.

The safety and effectiveness of cefiderocol was demonstrated in a pivotal study of 448 patients with cUTIs. Published results indicated that 73% of patients had resolution of symptoms and eradication of the bacteria approximately 7 days after completing treatment, compared with 55% in patients who received an alternative antibiotic.

The approval is for patients who have limited or no alternative treatment options and includes a label warning regarding cefiderocol’s higher all-cause mortality observed in comparison to patients treated with other antibiotics in a trial of critically ill patients having multidrug-resistant gram-negative bacterial infections (clinical trials. gov NCT02714595).

The cause of the increase in mortality has not been determined, according to the FDA. Some of the deaths in the study were attributable to worsening or complications of infection, or underlying comorbidities, in patients treated for hospital-acquired/ventilator-associated pneumonia (i.e., nosocomial pneumonia), bloodstream infections, or sepsis. Thus, safety and efficacy of cefiderocol has not been established for the treating these types of infections, according to the announcement.

Adverse reactions observed in patients treated with cefiderocol included diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion-site reactions, and candidiasis. The FDA added that cefiderocol should not be used in persons known to have a severe hypersensitivity to beta-lactam antibacterial drugs.

“A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA’s overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections,” John Farley, MD, acting director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research said in the FDA press statement.

Fetroja is a product of Shionogi.

[email protected]

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.