Ob.Gyn. News

Women with peripartum cardiomyopathy (PPCM), regardless of whether their left ventricular (LV) function recovers, may have a heightened risk for a relapse and other cardiovascular events if they become pregnant again later, a new study suggests.

Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.

In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.

The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.

Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”

Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.

The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”

To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.

Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).

The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”

Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).

The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)

All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)

The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.

Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.

Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.

Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.

It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.

The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”

No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.

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

Women with peripartum cardiomyopathy (PPCM), regardless of whether their left ventricular (LV) function recovers, may have a heightened risk for a relapse and other cardiovascular events if they become pregnant again later, a new study suggests.

Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.

In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.

The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.

Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”

Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.

The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”

To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.

Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).

The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”

Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).

The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)

All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)

The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.

Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.

Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.

Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.

It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.

The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”

No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.

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

Women with peripartum cardiomyopathy (PPCM), regardless of whether their left ventricular (LV) function recovers, may have a heightened risk for a relapse and other cardiovascular events if they become pregnant again later, a new study suggests.

Researchers looked at the long-term outcomes in a cohort of women who had developed PPCM and became pregnant again several years later, comparing those with LV function that had “normalized” in the interim against those with persisting LV dysfunction.

In their analysis, adverse maternal outcomes 5 years after an index pregnancy were significantly worse among those in whom LV dysfunction had persisted, compared with those with recovered LV function. The risk of relapsed PPCM persisted out to 8 years. Mortality remained high in both groups through the follow-up.

The study suggests that “women with PPCM need long-term follow-up by cardiology, as mortality does not abate over time,” Kalgi Modi, MD, Louisiana State University, Shreveport, said in an interview.

Women with a history of PPCM, she said, need “multidisciplinary and shared decision-making for family planning, because normalization of left ventricular function after index pregnancy does not guarantee a favorable outcome in the subsequent pregnancies.”

Dr. Modi is senior author on the study published online in the Journal of the American College of Cardiology.

The current findings are important to women with a history of PPCM who are “contemplating future pregnancy,” Afshan Hameed, MD, a maternal-fetal medicine specialist and cardiologist at the University of California, Irvine, said in an interview. The investigators suggest that “complete recovery of cardiac function after PPCM does not guarantee a favorable outcome in future pregnancy,” agreed Dr. Hameed, who was not involved in the current study. Future pregnancies must therefore “be highly discouraged or considered with caution even in patients who have recovered their cardiac function.”

To investigate the impact of PPCM on risk at subsequent pregnancies, the researchers studied 45 patients with PPCM who had gone on to have at least one more pregnancy, the first a median of 28 months later. Their mean age was 27 and 80% were Black; they were followed a median of 8 years.

Peripartum cardiomyopathy, defined as idiopathic heart failure with LV ejection fraction (LVEF) 45% or less in the last month of pregnancy through the following 5 months, was diagnosed post partum in 93.3% and antepartum in the remaining 6.7% (mean time of diagnosis, 6 weeks post partum).

The mean LVEF fell from 45.1% at the index pregnancy to 41.2% (P = .009) at subsequent pregnancies. The “recovery group” included the 30 women with LVEF recovery to 50% or higher after the index pregnancy, and the remaining 15 with persisting LV dysfunction – defined as LVEF < 50% – made up the “nonrecovery group.”

Recovery of LVEF was associated with a reduced risk of persisting LV dysfunction, the report states, at a hazard ratio of 0.08 (95% CI, 0.01-0.64; P = .02) after adjustment for hypertension, diabetes, and history of preeclampsia. But that risk went up sharply in association with illicit drug use, similarly adjusted, with an HR of 9.08 (95% CI, 1.38-59.8; P = .02).

The nonrecovery group, compared with the recovery group, experienced significantly higher rates of adverse maternal outcomes (53.3% vs. 20.0%; P = .04) – a composite endpoint that included relapse PPCM (33.3% vs. 3.3%; P = .01), HF (53.3% vs. 20.0%; P = .03), cardiogenic shock, thromboembolic events, and death – at 5 years. However, all-cause mortality was nonsignificantly different between the two groups (13.3% vs. 3.3%; P = .25)

All-cause mortality was nonsignificantly different between the two groups at a median of 8 years (20.0% vs. 20.0%; P = 1.00), and the difference in overall adverse maternal outcomes had gone from significant to nonsignificant (53.3% vs. 33.3%; P = .20). The difference in relapse PPCM between groups remained significant after 8 years (53.3% vs. 23.3%; P = .04)

The study is limited by its retrospective nature, a relatively small population, and lack of racial diversity, the report notes.

Indeed, most of the study’s subjects were Black, and previous studies have demonstrated a “different phenotypic presentation and outcome in African American women with PPCM, compared with non–African American women,” an accompanying editorial states.

Therefore, applicability of its findings to other populations “needs to be examined by urgently needed national prospective registries with long-term follow-up,” writes Uri Elkayam, MD, University of Southern California, Los Angeles.

Moreover, the study questions “whether the reverse remodeling and improvement of [LVEF] in women with PPCM represent a true recovery.” Prior studies “have shown an impaired contractile reserve as well as abnormal myocardial strain and reduced exercise capacity and even mortality in women with PPCM after RLV,” Dr. Elkayam notes.

It’s therefore possible – as with other forms of dilated cardiomyopathy – that LVEF normalization “does not represent a true recovery but a new steady state with subclinical myocardial dysfunction that is prone to development of recurrent [LV dysfunction] and clinical deterioration in response to various triggers such as long-standing hypertension, obesity, diabetes, illicit drug use,” and, “more importantly,” subsequent pregnancies.

The study points to “the need for a close long-term follow-up of women with PPCM” and provides “a rationale for early initiation of guideline-directed medical therapy after the diagnosis of PPCM and possible continuation even after improvement of LVEF.”

No funding source was reported. Dr. Modi and coauthors, Dr. Elkayam, and Dr. Hameed declare no relevant financial relationships.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

In the largest randomized controlled trial of an automated insulin delivery (AID) system (hybrid closed-loop) versus standard insulin delivery in pregnant women with type 1 diabetes, the automated CamAPS FX system prevailed.

The percentage of time spent in the pregnancy-specific target blood glucose range of 63-140 mg/dL (3.5-7.8 mmol/L) from 16 weeks’ gestation to delivery was significantly higher in women in the AID group.

Helen R. Murphy, MD, presented these topline findings from the Automated Insulin Delivery Amongst Pregnant Women With Type 1 Diabetes (AiDAPT) trial during an e-poster session at the annual scientific sessions of the American Diabetes Association.

The “hybrid closed-loop significantly improved maternal glucose and should be offered to all pregnant women with type 1 diabetes,” concluded Dr. Murphy, professor of medicine at the University of East Anglia and a clinician at Norfolk and Norwich University Hospital in the United Kingdom.

CamAPS FX is the only AID system approved in Europe and the United Kingdom for type 1 diabetes from age 1 and during pregnancy. The hybrid closed-loop system is not available in the United States but other systems are available and sometimes used off label in pregnancy. Such systems are sometimes known colloquially as an “artificial pancreas.”

The researchers said their findings provide evidence for the UK National Institute of Clinical Excellence (NICE) to recommend that all pregnant women with type 1 diabetes should be offered the CamAPS FX system.

Asked by an audience member about type 2 diabetes in pregnancy, Dr. Murphy said: “I don’t think we can necessarily extend these data to women with type 2 diabetes. We just don’t have enough data on glucose profiles in type 2 to train an algorithm yet.”  

However, the data provide support for earlier use of closed-loop therapy in type 1 diabetes, she said. “The ideal time to start closed-loop is not necessarily between 8 and 12 weeks. Half of all pregnancies are unplanned,” she noted, “so start [AID] as early as possible [in patients with type 1 diabetes].”
 

Two experts weigh in

Whether pregnant women with type 1 diabetes should be offered hybrid closed-loop therapy “depends,” said Anne L. Peters, MD, who was not involved with the research.

“It is all about being able to set [blood glucose] targets,” according to Dr. Peters, director of the University of Southern California Westside Center for Diabetes in Los Angeles.

USC Westside Center for Diabetes

Study rationale, method, and findings

Pregnant women with diabetes are advised to aim for very tight glucose targets throughout pregnancy and avoid hyperglycemia, to reduce risk of preterm delivery, neonatal weight > 90th percentile, and neonatal morbidity, according to Dr. Murphy and colleagues.

“However, despite increased use of [CGM], continuous subcutaneous insulin infusion (CSII), and improved insulin analogs, achieving and maintaining the recommended glucose targets remains challenging for most pregnant women with type 1 diabetes,” they wrote in their abstract.

Researchers randomized 124 women who had type 1 diabetes for at least 12 months, were at < 13 weeks’ to 6 days’ gestation, and had an A1c of 6.5% to < 10% who were taking intensive standard insulin therapy at nine antenatal clinics in the United Kingdom. Half of the women were using CSII and half were receiving multiple daily injections of insulin. 

As explained in the published study protocol, the women were randomized to continue their standard insulin delivery or switch to a closed-loop system consisting of the study insulin pump (Dana Diabecare RS), a CGM transmitter, and an app (CamAPS FX) on an Android smartphone that communicates wirelessly with the insulin pump and CGM transmitter.

Participants in both groups used the same CGM system and received support for insulin dose adjustment from their antenatal clinical care team.

They were a mean age of 31 years, had a mean A1c of 7.7%, and had had type 1 diabetes for 17 years on average. Their body mass index varied; 37% had normal weight, 27% had overweight, and 26% had obesity.

A significantly higher percentage of women in the AID group than in the control group had blood glucose in target range more than 70% of the time (46% vs. 10%; P < .001).

Compared with women in the control group, those in the AID group had larger reductions in hyperglycemia (–11%; P < .001), higher overnight time-in-range (13%; P < .001), and lower A1c (–0.34%; P < .001), without additional insulin, weight gain, or hypoglycemia.

The effect was consistent across clinical sites and maternal age and A1c categories.
 

Ongoing studies, off-label use

Hybrid closed-loop systems “including Tandem Control IQ, the Omnipod 5, and the Medtronic 780G give insulin continuously on the basis of values obtained from a sensor,” Dr. Peters explained in a recent commentary. “These aren’t fully closed-loop systems because the individual still has to interact with the system and give doses for meals, and then adjust doses for exercise.”

There are currently three studies using commercially available AID systems without pregnancy-specific glucose targets, in type 1 diabetes pregnancies, Dr. Polsky noted.

The Pregnancy Intervention With a Closed-Loop System (PICLS) trial used the Medtronic 670G system in pregnancy and was conducted in the United States. The Closed-Loop Insulin Delivery in Pregnant Women With Type 1 Diabetes (CRISTAL) study is using the Medtronic 780G system in pregnancy and is being conducted in Belgium and the Netherlands. And the Closed-Loop Insulin Delivery in Type 1 Diabetes Pregnancies (CIRCUIT) study is using the Tandem Control IQ system in pregnancy and is being conducted in Canada, she explained.

“The decision to continue to use or to initiate (off-label) use of any of these systems in pregnancy should be individualized, and pregnant individuals should make these decisions by working with an experienced endocrine/diabetes team,” Dr. Polsky stressed.

“The hope is that the results of these exciting trials will show safe and effective use of these systems throughout gestation with improvements in glucose control and quality of life,” she concluded.

The study was funded by the UK National Institute for Health Research, JDRF, and Diabetes Research and Wellness Foundation. Dr. Murphy has reported being on the advisory panel for Medtronic and receiving research support from Dexcom. Dr. Peters disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care, received a research grant from Abbott Diabetes Care, and received stock options from Teladoc and Omada Health. Dr. Polsky has disclosed that she is a contributing writer for diaTribe, was on a medical advisory board for Medtronic MiniMed, has received research funding from DexCom, Eli Lilly, JDRF, Leona & Harry Helmsley Charitable Trust, NIDDK, and Sanofi, and has received research support from Diasome Pharmaceuticals, LabStyle Innovation, Lexicon, Medtronic MiniMed, and Sanofi.

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

Oral contraceptive (OC) use has been linked to increased depression risk, especially within the first 2 years following initiation, new research shows.

In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.

The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.

areeya_ann/Thinkstock

Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.

This effect remained, even after analysis of potential familial confounding.

“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.

The study was published online in Epidemiology and Psychiatric Sciences.
 

Inconsistent findings

Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.

The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.

They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.

Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.

The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.

They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.

Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.

They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
 

Adolescents at highest risk

Of the participants, 80.6% had used OCs at some point.

The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).

Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).

Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).

Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.

OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).

Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).

In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.

The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
 

Flawed study

In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”

She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”

The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.

And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.

“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.

The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.

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

Oral contraceptive (OC) use has been linked to increased depression risk, especially within the first 2 years following initiation, new research shows.

In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.

The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.

areeya_ann/Thinkstock

Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.

This effect remained, even after analysis of potential familial confounding.

“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.

The study was published online in Epidemiology and Psychiatric Sciences.
 

Inconsistent findings

Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.

The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.

They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.

Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.

The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.

They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.

Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.

They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
 

Adolescents at highest risk

Of the participants, 80.6% had used OCs at some point.

The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).

Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).

Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).

Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.

OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).

Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).

In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.

The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
 

Flawed study

In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”

She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”

The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.

And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.

“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.

The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.

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

Oral contraceptive (OC) use has been linked to increased depression risk, especially within the first 2 years following initiation, new research shows.

In addition, OC use in adolescence has been tied to an increased risk for depression later in life. However, some experts believe the study’s methodology may be flawed.

The investigators tracked more than 250,000 women from birth to menopause, gathering information about their use of combined contraceptive pills (progesterone and estrogen), the timing of the initial depression diagnosis, and the onset of depressive symptoms that were not formally diagnosed.

areeya_ann/Thinkstock

Women who began using these OCs before or at the age of 20 experienced a 130% higher incidence of depressive symptoms, whereas adult users saw a 92% increase. But the higher occurrence of depression tended to decline after the first 2 years of use, except in teenagers, who maintained an increased incidence of depression even after discontinuation.

This effect remained, even after analysis of potential familial confounding.

“Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life,” Therese Johansson, of the department of immunology, genetics, and pathology, Science for Life Laboratory, Uppsala (Sweden) University, and colleagues wrote.

The study was published online in Epidemiology and Psychiatric Sciences.
 

Inconsistent findings

Previous studies suggest an association between adolescent use of hormonal contraceptives (HCs) and increased depression risk, but it’s “less clear” whether these effects are similar in adults, the authors wrote. Randomized clinical trials have “shown little or no effect” of HCs on mood. However, most of these studies didn’t consider previous use of HC.

The researchers wanted to estimate the incidence rate of depression associated with first initiation of OC use as well as the lifetime risk associated with use.

They studied 264,557 female participants in the UK Biobank (aged 37-71 years), collecting data from questionnaires, interviews, physical health measures, biological samples, imaging, and linked health records.

Most participants taking OCs had initiated use during the 1970s/early 1980s when second-generation OCs were predominantly used, consisting of levonorgestrel and ethinyl estradiol.

The researchers conducted a secondary outcome analysis on women who completed the UK Biobank Mental Health Questionnaire (MHQ) to evaluate depressive symptoms.

They estimated the associated risk for depression within 2 years after starting OCs in all women, as well as in groups stratified by age at initiation: before age 20 (adolescents) and age 20 and older (adults). In addition, the investigators estimated the lifetime risk for depression.

Time-dependent analysis compared the effect of OC use at initiation to the effect during the remaining years of use in recent and previous users.

They analyzed a subcohort of female siblings, utilizing “inference about causation from examination of familial confounding,” defined by the authors as a “regression-based approach for determining causality through the use of paired observational data collected from related individuals.”
 

Adolescents at highest risk

Of the participants, 80.6% had used OCs at some point.

The first 2 years of use were associated with a higher rate of depression among users, compared with never-users (hazard ration, 1.79; 95% confidence interval, 1.63-1.96). Although the risk became less pronounced after that, ever-use was still associated with increased lifetime risk for depression (HR, 1.05; 95% CI, 1.01-1.09).

Adolescents and adult OC users both experienced higher rates of depression during the first 2 years, with a more marked effect in adolescents than in adults (HR, 1.95; 95% CI, 1.64-2.32; and HR, 1.74; 95% CI, 1.54-1.95, respectively).

Previous users of OCs had a higher lifetime risk for depression, compared with never-users (HR, 1.05; 95% CI, 1.01-1.09).

Of the subcohort of women who completed the MHQ (n = 82,232), about half reported experiencing at least one of the core depressive symptoms.

OC initiation was associated with an increased risk for depressive symptoms during the first 2 years in ever- versus never-users (HR, 2.00; 95% CI, 1.91-2.10).

Those who began using OCs during adolescence had a dramatically higher rate of depressive symptoms, compared with never-users (HR, 2.30; 95% CI, 2.11-2.51), as did adult initiators (HR, 1.92; 95% CI, 2.11-2.51).

In the analysis of 7,354 first-degree sister pairs, 81% had initiated OCs. A sibling’s OC use was positively associated with a depression diagnosis, and the cosibling’s OC use was also associated with the sibling’s depression diagnosis. “These results support the hypothesis of a causal relationship between OC use and depression, such that OC use increases the risk of depression,” the authors wrote.

The main limitation is the potential for recall bias in the self-reported data, and that the UK Biobank sample consists of a healthier population than the overall U.K. population, which “hampers the generalizability” of the findings, the authors stated.
 

Flawed study

In a comment, Natalie Rasgon, MD, founder and director of the Stanford (Calif.) Center for Neuroscience in Women’s Health, said the study was “well researched” and “well written” but had “methodological issues.”

She questioned the sibling component, “which the researchers regard as confirming causality.” The effect may be “important but not causative.” Causality in people who are recalling retrospectively “is highly questionable by any adept researcher because it’s subject to memory. Different siblings may have different recall.”

The authors also didn’t study the indication for OC use. Several medical conditions are treated with OCs, including premenstrual dysphoric disorder, the “number one mood disorder among women of reproductive age.” Including this “could have made a huge difference in outcome data,” said Dr. Rasgon, who was not involved with the study.

Anne-Marie Amies Oelschlager, MD, professor of obstetrics and gynecology, University of Washington, Seattle, noted participants were asked to recall depressive symptoms and OC use as far back as 20-30 years ago, which lends itself to inaccurate recall.

And the researchers didn’t ascertain whether the contraceptives had been used continuously or had been started, stopped, and restarted. Nor did they look at different formulations and doses. And the observational nature of the study “limits the ability to infer causation,” continued Dr. Oelschlager, chair of the American College of Obstetrics and Gynecology Clinical Consensus Gynecology Committee. She was not involved with the study.

“This study is too flawed to use meaningfully in clinical practice,” Dr. Oelschlager concluded.

The study was primarily funded by the Swedish Research Council, the Swedish Brain Foundation, and the Uppsala University Center for Women ‘s Mental Health during the Reproductive Lifespan. The authors, Dr. Rasgon, and Dr. Oelschlager declared no relevant financial relationships.

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

In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?

Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.

John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.

Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.

Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.

Is Fusobacterium the new Helicobacter pylori?

The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples. 

They uncovered an interesting chain of cellular events:  macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis. 

Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.

“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”

After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.

To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.

Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.

“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”

Don’t write off gut microbiota

Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.

Dr. Ramakrishna Kommagani, Baylor College of Medicine Photography Services

Clues in genetic variants

Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.

What’s next?

The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. If a researcher identifies a factor that is more common in women with endometriosis – a particular bacterium or environmental exposure – proving causality is difficult. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.

Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.

Could stool samples be the answer?

The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.

“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said. 

Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.

“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.

Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).

Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.

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

In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?

Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.

John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.

Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.

Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.

Is Fusobacterium the new Helicobacter pylori?

The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples. 

They uncovered an interesting chain of cellular events:  macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis. 

Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.

“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”

After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.

To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.

Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.

“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”

Don’t write off gut microbiota

Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.

Dr. Ramakrishna Kommagani, Baylor College of Medicine Photography Services

Clues in genetic variants

Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.

What’s next?

The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. If a researcher identifies a factor that is more common in women with endometriosis – a particular bacterium or environmental exposure – proving causality is difficult. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.

Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.

Could stool samples be the answer?

The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.

“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said. 

Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.

“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.

Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).

Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.

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

In 1927, American gynecologist John Sampson published his theory of the etiology of endometriosis, postulating that retrograde flow of endometrial debris flows backward through the fallopian tubes during menses into the peritoneal cavity. Dr. Sampson’s notion remains the main paradigm today, mentioned still in recent articles on the topic, but it has a flaw: Although the theory may account for how endometrial tissue escapes the uterus, a 1984 study revealed that this phenomenon occurs in 90% of women. Why, then, do only 10% of women suffer from endometriosis?

Endometriosis describes a condition in which endometrial tissue lining the uterus is found outside the uterus. The disease can be painful, even crippling. As many as 30% of women in their reproductive years who have endometriosis are infertile as a consequence. The hallmarks of the condition are superficial peritoneal lesions of varying color, cysts in the ovaries, deeper nodules accompanied by scarring and adhesion, primarily in the pelvis but sometimes appearing outside the pelvis. The syndrome can be challenging to identify, requiring laparoscopy for definitive diagnosis.

John Sampson aside, scientists have struggled for the past century to identify the cause, or causes, of endometriosis. Hormones clearly play a role in its development, and women with endometriosis have an elevated risk of clear-cell and endometrioid ovarian cancer and autoimmune diseases. Immunodeficiency also could be to blame, if a faulty immune system fails to find and remove endometrial tissue outside of the uterus. A class of chemicals known as endocrine disruptors have been linked to endometriosis, but not definitively. Twin studies have demonstrated that as many as 50% of cases have a genetic basis, while mice with surgically induced endometriosis have been found to have a higher ratio of harmful to beneficial bacteria in their gut.

Several studies published this year point to new insights into the old mystery – with possible implications for ways to treat the disorder.

Perhaps the most surprising came out earlier this year in Science Translational Medicine, as a team of researchers in Japan reported that invasive infection by bacteria of the genus Fusobacterium may cause at least some cases of endometriosis.

Is Fusobacterium the new Helicobacter pylori?

The researchers, from Nagoya University, are the first to suggest that not only might a single bacterial genus cause endometriosis, but that antibiotic treatment could prevent progression of the disease. Using endometrial tissue obtained from 79 women undergoing hysterectomy for endometriosis and 76 women undergoing hysterectomy for other reasons (such as cervical cancer), the team started with gene expression profiling to explore differences between the two sets of samples. 

They uncovered an interesting chain of cellular events:  macrophages found in endometriotic lesions were secreting transforming growth factor-beta (TGF-beta). TGF-beta in turn stimulated high levels of expression of a gene called TAGLN in fibroblast cells from women with endometriosis but not in fibroblasts from women without endometriosis. 

Turning on TAGLN transformed these previously inactive cells into active myofibroblasts, leading to increased proliferation, mobility, and attachment to mesothelial cells, the layer of cells that line body cavities and internal organs. In short, they identified some key players in an environment that seemed very favorable to the development of endometriosis.

“So, the question is: Why are macrophages activated?” said Yutaka Kondo, MD, PhD, the senior author of the study and a professor in the division of cancer biology at the Nagoya (Japan) University Graduate School of Medicine. “We think that there are always bacteria in the endometrium.”

After reviewing data from a previously published study, they used quantitative polymerase chain reaction to rule out one candidate, Erysipelothrix, but scored on their next attempt, identifying Fusobacterium species in endometrial tissue from 64% of the women with endometriosis, compared with fewer than 10% of the controls.

To confirm that the bacteria could cause disease and were not simply bystanders, Dr. Kondo’s team turned to a mouse model for endometriosis, in which endometrial cells are surgically removed from the uteri of mice and injected into the peritoneum of recipient mice, leading to the formation of endometriotic lesions. When mice received further injections of uterine tissue from mice that were infected with F. nucleatum, their lesions were more numerous when compared with mice that received injections of uninfected uterine tissue. Furthermore, antibiotic treatment with metronidazole or chloramphenicol immediately after surgery largely prevented progression to endometriosis, Dr. Kondo and his colleagues reported.

Dr. Kondo likened this relationship between Fusobacterium and endometriosis to that of the link between Helicobacter pylori and peptic ulcers but acknowledged that he doesn’t have all the answers.

“We need more clinical trials, and also we have to know what kind of treatment might be the most effective for the treatment of endometriosis,” Dr. Kondo said, pointing out that other therapies should still be pursued in addition to antibiotics, as not all the samples from women with endometriosis harbored Fusobacterium. “It might be possible that other mechanisms are also involved.”

Don’t write off gut microbiota

Ramakrishna Kommagani, PhD, associate professor of pathology and immunology at Baylor College of Medicine in Houston, agreed. “Endometriosis is a complex disease, which appears to be impacted by many factors, including genetic, epigenetic, and environmental factors,” Dr. Kommagani said.

Dr. Ramakrishna Kommagani, Baylor College of Medicine Photography Services

Clues in genetic variants

Krina Zondervan, DPhil, professor and head of the department of reproductive and genomic epidemiology at the University of Oxford (England), focuses on genomic, molecular, and epidemiologic approaches to understanding endometriosis.

What’s next?

The chief limitation of human studies looking at mechanisms of endometriosis is that they are correlational: Tissue samples are collected from women with and without endometriosis, often through an invasive procedure such as laparoscopy or biopsy, at one point in time. If a researcher identifies a factor that is more common in women with endometriosis – a particular bacterium or environmental exposure – proving causality is difficult. Currently, the best tools for proving causation are animal models of endometriosis, such as the those used by Dr. Kondo’s and Dr. Kommagani’s teams.

Better diagnostic tools would solve that problem. The ultimate goal is a noninvasive test for endometriosis that would allow clinicians to follow women over time and permit the monitoring of disease progression, or regression, without the need for painful procedures. Such a diagnostic tool would facilitate rigorous longitudinal studies evaluating mechanisms of disease, as well as monitoring outcomes of clinical trials of new treatments.

Could stool samples be the answer?

The Japanese team found that women harboring Fusobacterium in endometrial tissue also had Fusobacterium in vaginal samples taken at the time of their hysterectomy – and stool samples can pick up changes in the gut microbiome.

“Vaginal swab or stool tests are probably the best and easiest for noninvasive early detection,” Dr. Kommagani said. 

Spit tests for DNA would be even easier to obtain. Polygenic risk scores could be developed to estimate an individual’s risk of disease based on the number of variants, but Dr. Zondervan cautioned that not all the genes that account for endometriosis are known.

“The things that we found altogether explain about 5% of disease variability, basically – which is still not an awful lot,” she said.

Dr. Kondo’s work was supported by the Grant-in-Aid for Scientific Research, the Japan Society for the Promotion of Science, and the Research Grant of the Princess Takamatsu Cancer Research Fund. A patent method for detecting bacteria of genus Fusobacterium in order to diagnose endometriosis (WO2023/ 042714), was submitted (international publication date, March 23, 2023).

Dr. Kommagani’s work was funded, in part, by National Institutes of Health/National Institute of Child Health and Human Development grants R01HD102680, R01HD065435, and R00HD080742. He has no other conflicts of interest. Dr. Zondervan received funding from the Wellcome Trust (216767; 104036; 084766; 212904; 076113 and 085475) and also reported grants from Bayer AG, AbbVie, Volition Rx, MDNA Life Sciences, and Roche Diagnostics outside the submitted work.

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Ore.

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

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

A smartwatch can tell a lot about a person’s health, but for guarding against big threats like diabetes and heart disease, blood tests remain the gold standard – for now. 

Someday, a wearable patch could give patients and doctors the same information, minus the poke in the arm and the schlep to the medical lab. 

The patch will track markers in interstitial fluid. 

Continuous glucose monitors have already provided this glimpse into the future, by using interstitial fluid to track blood glucose levels in real time. 

Now scientists are asking: What else could this tech help us measure? 

“The vision is eventually to develop a lab under the skin,” said Joseph Wang, PhD, professor of nanoengineering at the University of California San Diego.

The result: All your patients’ lab work – cholesterol, hormones, electrolytes, and more – could become do-it-yourself, easing burdens on the health care system and empowering patients with real-time, clinical-grade information about their health. 
 

How does it work?

Sweat and saliva may be easier to get to, but interstitial fluid is a better mirror for blood. It leaks from tiny blood vessels (capillaries), and it carries nutrients to and removes waste from your skin.

To capture this fluid, each monitor has either a tiny wire or an array of less-than-a-millimeter-long microneedles that penetrate the skin for days, weeks, or however long you wear it. “You don’t feel it,” Dr. Wang said. “Once you place it on the skin, you forget about it.”

The microneedles or wires are made from a polymer that sucks up the fluid, which flows to a biochemical sensor targeting the marker you want to measure.

The earliest patents for this technology date back to the 1990s (the first wearable glucose monitors for home use rolled out in the 2000s), but sensors have come a long way since then, becoming smaller, more accurate, and more sophisticated.

Glucose sensors use an enzyme that reacts to glucose to reveal its concentration in the blood. Researcher Jason Heikenfeld, PhD, and his team at the University of Cincinnati focus on “aptamers,” short single strands of DNA that bind to target molecules. “You can leverage the body’s own ability to generate stuff to grab a needle in a haystack,” he said.   
 

The bigger picture

As our population ages and health care costs spiral, and our medical infrastructure and labor force are stretched thin, we’re seeing a push for decentralized medicine, Dr. Heikenfeld said. Like other at-home monitoring technologies, interstitial fluid sensing promises convenience and better access to care. 

“There’s a lot you can do over telemedicine, over the phone,” said Justin T. Baca, MD, PhD, associate professor at the University of New Mexico, Albuquerque. “But we still haven’t figured out how to collect reliable biosamples and analyze them remotely.”

Unlike a traditional blood test, which gives a health snapshot for a single point in time, these devices track data continuously, revealing trends and helping you spot oncoming threats earlier. 

Take ketones, for example. Dr. Baca and others are using interstitial fluid to continuously detect ketone levels in the blood, potentially enabling us to catch diabetic ketoacidosis sooner. 

“It’s potentially like an early warning sign that somebody needs to get either checked out or get rehydrated or get some insulin; kind of an early diagnostic to avoid hospital visits later on,” Dr. Baca said. 

Here’s what else this tech could help us do:

Chronic disease management

Seeing the health impact of medication and diet in real time could motivate patients to stick to their treatment plans, Dr. Heikenfeld said. Researchers in Taiwan are developing a test that could help people with chronic kidney disease track levels of cystatin C, a protein that goes up as kidney function declines. Heart disease patients could watch their cholesterol levels drop over time, and of course, diabetes patients can already track glucose. 

Prescription drug monitoring

Providers could monitor drug levels in a patient’s body – like antibiotics for an infection – to see how it’s being metabolized, and adjust the dose as needed, Dr. Heikenfeld said. 

Stress and hormone therapy

Interstitial fluid could help us measure hormone levels, such as the stress hormone cortisol. 

Scientists in the United Kingdom and Norway developed a waist-worn device that collects interstitial fluid samples continuously for up to 3 days. In their study, samples were sent out for analysis, but someday the device could be equipped with a sensor to monitor a single hormone in real time, said study author Thomas Upton, PhD, a clinical research fellow at the University of Bristol in England. “There is a lot of interest in real-time cortisol monitoring,” he said. 

Among those who could benefit: patients with hormone deficiencies, night shift workers with disturbed circadian rhythms, or anyone who wants to keep tabs on their stress response. 

Human performance and wellness

Athletes could use glucose and lactate monitors to optimize training, recovery time, and diet. For those on the keto diet, a monitor could help them adjust their carb intake based on their ketone levels. Abbott’s Analyte Ventures group is working on blood alcohol sensors, helpful to anyone who wants to avoid overindulging.  
 

When will this be ready for clinical use?

Early research has been promising, but much more is needed before interstitial fluid sensors can be verified and approved. 

Manufacturing will be a challenge. Producing these sensors at scale, without sacrificing consistency or quality, won’t be cheap, said Dr. Heikenfeld. Today’s continuous glucose monitors took decades and hundreds of millions of dollars to develop. 

Still, the groundwork has been laid. 

“As we all pivot more towards interstitial fluid, there’s a proven roadmap of success that the big diagnostic companies over decades have cut their teeth on,” said Dr. Heikenfeld. 

For now, scientists are refining sensors and figuring out how to protect them from other body fluids while in use, Dr. Wang said. But if it all comes together, the result could be game-changing.

Dr. Wang’s lab is developing a system that can monitor glucose and lactate or glucose and alcohol – which could become available in as little as 2 years, he said. 

In the next decade, Dr. Wang predicted, we’ll be able to measure a dozen markers with one simple patch.

A version of this article originally appeared on WebMD.com.

Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.

Investigators found that women in their 50s who took hormone therapy (HT) for menopausal symptoms had a 24% increased risk of developing dementia and Alzheimer’s disease (AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.

However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.

“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.

Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.

The findings were published online in BMJ.
 

Conflicting findings

Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.

Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.

To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.

Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.

The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.

Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.

The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
 

Longer use equals greater risk

Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).

The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.

Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.

Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).

Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.

The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
 

No causal relationship

In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.

“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.

Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”

There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.

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

Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.

Investigators found that women in their 50s who took hormone therapy (HT) for menopausal symptoms had a 24% increased risk of developing dementia and Alzheimer’s disease (AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.

However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.

“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.

Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.

The findings were published online in BMJ.
 

Conflicting findings

Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.

Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.

To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.

Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.

The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.

Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.

The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
 

Longer use equals greater risk

Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).

The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.

Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.

Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).

Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.

The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
 

No causal relationship

In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.

“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.

Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”

There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.

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

Short-term and cyclical use of estrogen and progestin therapy for menopausal symptoms is linked to an increased risk of dementia, results of a large observational study show.

Investigators found that women in their 50s who took hormone therapy (HT) for menopausal symptoms had a 24% increased risk of developing dementia and Alzheimer’s disease (AD) 20 years later, compared with those who didn’t use HT. The risk was present even in women who used HT for brief periods at menopause onset.

However, both the investigators and experts not involved in the research caution that further studies are needed to explore whether the increased risk of dementia stems from HT use or whether women in need of HT have other underlying dementia risk factors.

“We cannot guarantee that our findings illustrate a causal relationship or if they represent underlying disposition to dementia in women in need of [HT],” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Research Centre at Copenhagen University Hospital Rigshospitalet, told this news organization.

Still, he added, the findings supported evidence from the Women’s Health Initiative Memory Study (WHIMS), the largest randomized trial on menopausal hormone therapy and dementia.

The findings were published online in BMJ.
 

Conflicting findings

Before WHIMS was published in 2003, HT was widely prescribed to relieve menopausal symptoms. However, WHIMS, which included more than 4,000 women aged 65 years or older, revealed that HT was associated with a twofold increased risk of dementia.

Studies published since then have yielded mixed results, adding to the controversy surrounding the safety of HT.

To discover whether age of initiation or length of duration of HT affects health outcomes, Dr. Pourhadi and his team undertook the observational study.

Between 2000 and 2018, the researchers tracked more than 60,000 Danish women aged 50-60 years using diagnosis and prescription information from Denmark’s National Registry of Patients.

The registry records showed that nearly 5,600 women developed dementia and 56,000 did not develop dementia. Of the 5,600 women with dementia, 1,460 had a diagnosis of AD.

Nearly 18,000 participants in the study sample received HT – 1,790 (29%) in the dementia group and 16,150 (32%) in the control group. Half started treatment before age 53 years and half stopped within 4 years. Roughly 90% used oral medications, which included a combination of estrogen and progestin.

The median age at which participants started HT was 53 years for both cases and controls, and the median duration of use was 4 years.
 

Longer use equals greater risk

Compared with those who did not use HT, those who used estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia (hazard ratio, 1.24; 95% confidence interval, 1.17-1.44).

The increased dementia risk was similar between continuous (estrogen and progestin taken daily) and cyclic (daily estrogen with progestin taken 10-14 days a month) treatment regimens.

Longer durations of HT use were associated with increased risk, ranging from a 21% increased risk (HR, 1.21; 95% CI, 1.09-1.35) for those who used it for 1 year or less to a 74% increased risk (HR, 1.74; 95% CI, 1.45-2.10) for use lasting 12 years or more.

Women who started HT between the age of 45 and 50 had a 26% increased risk of developing all-cause dementia (HR, 1.26; 95% CI, 1.13-1.41) while women who initiated HT between age 51 and 60 had a 21% greater risk (HR, 1.21; 95% CI, 1.12-1.29).

Progestin-only or vaginal-estrogen-only therapy was not associated with the development of dementia.

The investigators noted that because this is an observational study, “further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect.”
 

No causal relationship

In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology at the Mayo Clinic, Rochester, Minn., noted that three clinical trials, including the WHIMS of Younger Women (WHIMS-Y) in 2013, did not show a link between cognitive function and HT.

“Although [Dr.] Pourhadi and colleagues’ study was done carefully using national registries, the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk. These findings cannot inform shared decision-making about use of hormone therapy for menopausal symptoms,” she states in the editorial.

Also commenting on the findings, Amanda Heslegrave, PhD, a senior research fellow at the U.K. Dementia Research Institute, London, said in a release from the U.K.’s Science Media Centre that while the study “may cause alarm for women taking [HT], it highlights just how much we still don’t know about the effects of hormones on women’s brain health, and with promising treatments on the horizon, it should be a call to action to make this a priority area of research.”

There was no specific funding for the study. Dr. Kantarci reported working on an unpaid educational activity on Alzheimer’s disease for Biogen and is the PI on a study of a PET imaging ligand for Alzheimer’s disease, to which Eli Lilly and Avid Radiopharmaceuticals donated supplies.

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

The U.S. Supreme Court ruled on June 29 that using race as a factor in college admissions is unconstitutional, rolling back more than 40 years of affirmative action standards and changing how medical schools evaluate applicants to attract students from diverse backgrounds.  

Jesse M. Ehrenfeld, MD, MPH, president of the American Medical Association, said in a prepared statement that the Supreme Court ruling will result in a less diverse physician workforce, which is “bad for health care, bad for medicine, and undermines the health of our nation.” He cited the AMA’s recent adoption of a policy advising medical schools to increase enrollment of people from racial and ethnic groups traditionally underrepresented in medicine – even if that means considering race as a factor in admissions criteria.

“Supporting racial and ethnic diversity in the health professions – spanning classrooms, labs, and clinical settings – enriches the educational experiences of all medical and health professions students and the teaching experiences of faculty, and it is essential to improving the overall health of our nation,” the Association of American Medical Colleges (AAMC) said in a prepared statement. The AAMC said it was “deeply disappointed” in the court’s decision and will continue to pursue efforts to improve diversity among medical students and physicians.

The American Medical Student Association also denounced the Supreme Court decision. “As future physicians committed to justice and equality, we are profoundly outraged ... We strongly support increased representation of minority students in all levels of education, including colleges and medical schools. By fostering diversity and inclusion, institutions have the power to create more empathetic and inclusive learning environments,” the organization said in a press release.

“Diversity in the health care workforce not only benefits underserved patients but improves care for all patients” by increasing understanding and empathy for people of various cultures, Omar T. Atiq, MD, president of the American College of Physicians, said in a press release.

The Supreme Court ruling stems from a lawsuit by the Students for Fair Admissions against Harvard University and the University of North Carolina. The lawsuit alleges that considering race in the college admission process constitutes discrimination and violates the Equal Protection Clause.

Chief Justice John Roberts, who delivered the court’s decision, stated that an applicant’s personal experiences should carry the most weight in admission decisions and that historically, universities have “wrongly concluded that the touchstone of an individual’s identity is not challenges bested, skills built, or lessons learned, but the color of their skin. Our constitutional history does not tolerate that choice.”

Still, Justice Roberts said the opinion does not prohibit universities from considering how race has affected an applicant’s life, “be it through discrimination, inspiration, or otherwise.”

Diversity in medical schools increased last year, with more Black, Hispanic, and female students applying and enrolling. But continued diversity efforts were expected to prove challenging with affirmative action off the table, according to an amicus brief filed last year by the AMA, the AAMC, and dozens of other professional health care organizations.

The brief supported continued use of race in college admissions, stating that eliminating that factor could slow efforts to achieve greater health equity because fewer doctors would be training and working with colleagues from diverse backgrounds.

Several universities with medical programs, such as Yale and Johns Hopkins universities, filed a separate brief citing similar concerns. After the June 29 decision, Harvard and the University of North Carolina released statements stating they would comply with the ruling.

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