Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Even though men in midlife have more cardiovascular (CV) conditions and risk factors than women of the same age, women are more affected by these conditions in terms of cognitive decline, new research suggests.

Analyses of almost 1,400 participants in the population-based Mayo Clinic Study of Aging showed that diabetes, dyslipidemia, and coronary heart disease (CHD) all had stronger associations with global cognitive decline in women than in men.

“All men and women should be treated for cardiovascular risk factors and conditions, but this study really highlights the importance of very early and perhaps more aggressive treatment in women with these conditions,” co-investigator Michelle M. Mielke, PhD, professor of epidemiology and neurology, Mayo Clinic, Rochester, Minn., told this news organization.

The findings were published online Jan. 5 in Neurology.
 

Assessing sex differences

Most previous studies in this area have focused on CV risk factors in midlife in relation to late-life dementia (after age 75) or on late-life vascular risk factors and late-life dementia, Dr. Mielke noted.

However, a few recent studies have suggested vascular risk factors can affect cognition even in midlife. The current investigators sought to determine whether there are sex differences in these associations.

They assessed 1,857 nondemented participants aged 50 to 69 years from the Mayo Clinic Study on Aging. The mean education level was 14.9 years, and the mean body mass index (BMI) was 29.7.

Among the participants, 78.9% had at least one CV condition or risk factor, and the proportion was higher in men than women (83.4% vs. 74.5%; P < .0001).

Frequency of each individual CV condition or risk factor was also higher in men than women, and they had more years of education and higher BMI but took fewer medications.

Every 15 months, participants had an in-person interview and physical examination that included a neurologic assessment and short test of memory.

The neuropsychological battery included nine tests across four domains: memory, language, executive function, and visuospatial skills. Researchers calculated z-scores for these domains and for global cognition.
 

Multiple cognitive domains

Whereas this study evaluated multiple cognitive domains, most previous research has focused on global cognitive decline and/or decline in only one or two cognitive domains, the investigators note.

They collected information from medical records on CV conditions such as CHD, arrhythmias, congestive heart failure, peripheral vascular disease (PVD), and stroke; and CV risk factors such as hypertension, diabetes, dyslipidemia, smoking status, and BMI.

Because of the small number of patients with stroke and PVD, these were classified as “other cardiovascular conditions” in the statistical analysis.

Researchers adjusted for sex, age, years of education, depressive symptoms, comorbidities, medications, and apolipoprotein E (APOE) genotyping. The mean follow-up was 3 years and did not differ by sex.

As some participants didn’t have a follow-up visit, the current analysis included 1,394 individuals. Those without follow-up visits were younger, had less education and more comorbidities, and took more medications compared with those with a follow-up.

Results showed most CV conditions were more strongly associated with cognitive function among women than men. For example, CHD was associated with global decline only in women (P < .05).

CHD, diabetes, and dyslipidemia were associated with language decline in women only (all, P < .05), but congestive heart failure was significantly associated with language decline in men only.

Dr. Mielke cautioned about reading too much into the language results for women.

“It’s an intriguing finding and definitely we need to follow up on it,” she said. However, “more studies are needed to examine sex differences before we start saying it only has an effect on language.”
 

‘Treat aggressively and right away’

The researchers were somewhat surprised by the study findings. Because there is a higher prevalence of CV conditions and risk factors in men, they presumed men would be more affected by these conditions, said Dr. Mielke.

“But that’s not what we saw; we saw the reverse. It was actually the women who were affected more by these cardiovascular risk factors and conditions,” she said.

As midlife is when women enter menopause, fluctuating estrogen levels may help explain the differential impact on cognition among women. But Dr. Mielke said she wants to “move beyond” just looking at hormones.

She pointed out there are a variety of psychosocial factors that may also contribute to an imbalance in the cognitive impact of CV conditions on women.

“Midlife is when many women are still taking care of their children at home, are also taking care of their adult parents, and may be undergoing more stress while continuing to do a job,” Dr. Miekle said.

Structural brain development and genetics may also contribute to the greater effect on cognition in women, the investigators note.

Dr. Mielke stressed that the current study only identifies associations. “The next steps are to understand what some of the underlying mechanisms for this are,” she said.

In the meantime, these new results suggest middle-aged women with high blood pressure, cholesterol, or glucose measures “should be treated aggressively and right away” said Dr. Mielke.

“For example, for women who are just starting to become hypertensive, clinicians should treat them right away and not watch and wait.”

Study limitations cited include that its sample was limited to Olmsted County, Minnesota – so results may not be generalized to other populations. Also, as researchers combined PVD and stroke into one group, larger sample sizes are needed, especially for stroke. Another limitation was the study did not have information on duration of all CV conditions or risk factors.
 

Helpful for tailoring interventions?

Commenting on the study, Glen R. Finney, MD, director, Memory and Cognition Program, Geisinger Health Clinic, Wilkes-Barre, Pennsylvania, said the results are important.

“The more we understand about risk factors for the development of Alzheimer’s disease and related dementias, the better we understand how we can reduce the risks,” said Dr. Finney, who was not involved with the research.

Awareness that CV conditions are major risk factors in midlife has been “definitely rising,” said Dr. Finney. “Many studies originally were looking at late life and are now looking more at earlier in the disease process, and I think that’s important.”

Understanding how sex, ethnicity, and other demographic variables affect risks can help to “tailor interventions” for individual patients, he said.

The study was supported by the National Institutes of Health, the GHR Foundation, and the Rochester Epidemiology Project. Dr. Mielke is a consultant for Biogen and Brain Protection Company and is on the editorial boards of Neurology and Alzheimer’s and Dementia. Dr. Finney has reported no relevant financial relationships.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors show “remarkable consistency of class benefit” for improving cardiovascular outcomes in high-risk people across age, sex, and race/ethnicity categories.

The findings, from a meta-analysis of 10 major randomized clinical trials, were published online Jan. 5, 2021, in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at Southern Illinois University, Springfield, and colleagues.

“Our meta-analysis evaluated a wide spectrum of efficacy outcomes, further characterizing the primary outcome in different subgroups from several well-designed large clinical trials. It supports that SGLT2 inhibitors have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality, including the prevention of [hospitalization for heart failure] and reducing all-cause mortality in selected patients,” Dr. Bhattarai and colleagues wrote.

The cardiovascular outcomes of SGLT2 inhibitor therapy, they noted, “can be compared across all trials, and it demonstrates remarkable consistency of class benefit, despite the variations in populations enrolled.”

However, they also noted that SGLT inhibitors did not reduce the risk of acute MIn overall, and that most of the trials were short term, with a mean follow-up of just 2.3 years.
 

Ten trials, consistent cardiovascular benefits

Dr. Bhattarai and colleagues searched the literature through Jan. 10, 2021, as well as meeting presentations and other sources. They identified 10 placebo-controlled, randomized clinical trials in which participants had atherosclerotic cardiovascular disease or ASCVD risk factors, diabetes, or heart failure. Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo.

The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors, compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 (P < .001). Both individual outcomes were lower in the SGLT2-inhibitor group, with a number needed to treat of 5.7 (P < .001).

Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal MI, or nonfatal stroke. Those events occurred in 9.82% versus 10.22%(OR, 0.90; P = .03).

Hospitalizations and ED visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs. 6.81%; OR, 0.67; P < .001), as was cardiovascular death (4.65% vs. 5.14%; OR, 0.87; P = .009). The reduction in heart failure is likely caused by a combination of a natriuretic effect and reduced interstitial fluid, along with inhibition of cardiac fibrosis, the authors said.

On the other hand, no reductions were seen in acute MI, evaluated in five of the studies. That event occurred in 4.66% taking SGLT2 inhibitors, compared with 4.70% of the placebo group, a nonsignificant difference with an OR of 0.95 (P = 0.22). This is likely because of the fact that SGLT2 inhibitors don’t have known antianginal properties or vasodilatory effects, they don’t reduce myocardial oxygen consumption, and they don’t prevent cardiac muscle remodeling, they noted.

All-cause mortality was significantly lower with SGLT2 inhibitors, though, at 7.09% versus 7.86% (odds ratio, 0.87; P = .004).
 

Benefits seen across age, sex, and race/ethnicity subgroups

While no differences in benefit were found between men and women when compared with placebo groups, the rates of cardiovascular death or heart failure hospitalizations were slightly higher in men than in women (9.01% [OR, 0.75; P < .001] vs. 5.34% [OR, 0.78; P = .002]).

By age, SGLT2 inhibitors benefited people both those younger than 65 years and those aged 65 years and older, although the primary outcome was slightly lower in the younger group (6.94% [OR, 0.79; P < 0.001] vs. 10.47% [OR, 0.78; P < .001]).

And by race, similar benefits from SGLT2 inhibitors were seen among individuals who were White, compared with those who were Asian, Black, or of other race/ethnicity, with event rates of 8.77% (OR, 0.82; P < .001) and 8.75% (OR, 0.66; P = .06), respectively.

“Owing to the short-term trial durations, future long-term prospective studies and postmarketing surveillance studies are warranted to discover the rate of cardiovascular outcomes,” Dr. Bhattarai and colleagues concluded.

The authors have no disclosures.

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

FROM FRONTIERS IN PHYSIOLOGY

Researchers have identified a potential cause of molar hypomineralization (MH), or “chalky teeth,” an underrecognized condition affecting one in five children worldwide. The discovery could lead to preventive medical therapies to reduce dental caries and extractions, they said.

According to a team led by biochemist Michael J. Hubbard, BDS, PhD, professor in the department of medicine, dentistry, and health sciences at the University of Melbourne, the “groundbreaking” research found that the failure of enamel to adequately harden is associated with exposure to serum albumin while teeth are developing. The blood protein “poisons” the growth of mineral crystals rather than injure the cells that deposit enamel, they reported.

The investigators, including researchers from Chile, said their findings hold promise for better clinical management of MH and open a new door into research on the broader pathogenesis and causes of the condition.

“We hope this breakthrough will eventually lead to medical prevention of MH, prompting global health benefits including major reductions in childhood tooth decay,” they wrote in an article published online Dec. 21 in Frontiers in Physiology.
 

More than cosmetic

Chalky teeth, characterized by discolored enamel spots, are not merely a cosmetic problem. The condition can lead to severe toothache, painful eating, tooth decay, and even abscesses and extractions. Although its triggers have eluded dental research for a century, Dr. Hubbard’s group said fossilized blood proteins such as albumin in the tooth appear to be at least one cause.

Biochemical evidence indicates that serum albumin surrounding developing teeth is normally excluded from enamel, Dr. Hubbard said in an interview. “Given that albumin binds strongly to hydroxyapatite-based mineral and blocks its growth, we infer that the epithelial barrier – the enamel-forming cells termed ameloblasts and normally responsible for excluding albumin – must break down in places in response to medical triggers.”

This breach enables localized infiltration of albumin, which then blocks further hardening of soft, immature enamel, leading to residual spots or patches of chalky enamel once the tooth eventually erupts into the mouth. “In other words, we infer that chalky enamel spots coincide with localized breaches of an epithelial barrier that are triggered by yet-to-be determined systemic insults,” he said.

Joseph Brofsky, DMD, section head of pediatric dentistry at North Shore LIJ Cohen Children’s Medical Center of New York, in Queens, agreed that that the definitive cause of MH has evaded identification for a hundred years. However, he expressed skepticism about the fossilized blood protein hypothesis.

“That’s a long shot. It’s a possibility, and I’m not ruling it out, but we’re not 100% sure,” said Dr. Brofsky, who was not involved in the research.

In his experience, MH is somewhat less prevalent in the United States, affecting about 1 in 10 children here, which is about half the global rate. “But it’s a problem, and we wish it would go away, but before we know beyond a reasonable doubt what causes this condition, it’s going to be hard to stop it.”

Most cases of MH involve hypomineralization of the 6-year molars, the first adult molars to erupt, but the process starts at birth. “For 6-year molars, normal hardening of dental enamel takes place from the early postnatal period through infancy,” Dr. Hubbard said.

The 2-year and 12-year molars are affected about half as frequently as their 6-year counterparts, “so this extends the medical-risk window out to early school days, and slightly back to the perinatal period for the 12-year and 2-year molars, respectively,” he said.

A critical question is which childhood illnesses are most likely to set the stage for MH, he added. “Forty-plus years of epidemiology have failed to nail a specific cause or causal association. But given the high prevalence of MH – 20% in otherwise healthy kids – naturally we suspect some common illnesses are the culprits,” he said. “But which diseases, which medications, and which combinations?”

Dr. Hubbard’s advice to pediatricians is to be alert to MH: “If you’re inspecting a child’s throat, then why not look at their back teeth, too – particularly when they’re getting their new molars at 2, 6, and 12 years?”

The study was supported by the Melbourne Research Unit for Facial Disorders Department of Pharmacology & Therapeutics, Department of Paediatrics, and Faculty of Medicine, Dentistry, and Health Sciences at the University of Melbourne. The authors and Dr. Brofsky have disclosed no relevant financial relationships.

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

FROM FRONTIERS IN PHYSIOLOGY

Researchers have identified a potential cause of molar hypomineralization (MH), or “chalky teeth,” an underrecognized condition affecting one in five children worldwide. The discovery could lead to preventive medical therapies to reduce dental caries and extractions, they said.

According to a team led by biochemist Michael J. Hubbard, BDS, PhD, professor in the department of medicine, dentistry, and health sciences at the University of Melbourne, the “groundbreaking” research found that the failure of enamel to adequately harden is associated with exposure to serum albumin while teeth are developing. The blood protein “poisons” the growth of mineral crystals rather than injure the cells that deposit enamel, they reported.

The investigators, including researchers from Chile, said their findings hold promise for better clinical management of MH and open a new door into research on the broader pathogenesis and causes of the condition.

“We hope this breakthrough will eventually lead to medical prevention of MH, prompting global health benefits including major reductions in childhood tooth decay,” they wrote in an article published online Dec. 21 in Frontiers in Physiology.
 

More than cosmetic

Chalky teeth, characterized by discolored enamel spots, are not merely a cosmetic problem. The condition can lead to severe toothache, painful eating, tooth decay, and even abscesses and extractions. Although its triggers have eluded dental research for a century, Dr. Hubbard’s group said fossilized blood proteins such as albumin in the tooth appear to be at least one cause.

Biochemical evidence indicates that serum albumin surrounding developing teeth is normally excluded from enamel, Dr. Hubbard said in an interview. “Given that albumin binds strongly to hydroxyapatite-based mineral and blocks its growth, we infer that the epithelial barrier – the enamel-forming cells termed ameloblasts and normally responsible for excluding albumin – must break down in places in response to medical triggers.”

This breach enables localized infiltration of albumin, which then blocks further hardening of soft, immature enamel, leading to residual spots or patches of chalky enamel once the tooth eventually erupts into the mouth. “In other words, we infer that chalky enamel spots coincide with localized breaches of an epithelial barrier that are triggered by yet-to-be determined systemic insults,” he said.

Joseph Brofsky, DMD, section head of pediatric dentistry at North Shore LIJ Cohen Children’s Medical Center of New York, in Queens, agreed that that the definitive cause of MH has evaded identification for a hundred years. However, he expressed skepticism about the fossilized blood protein hypothesis.

“That’s a long shot. It’s a possibility, and I’m not ruling it out, but we’re not 100% sure,” said Dr. Brofsky, who was not involved in the research.

In his experience, MH is somewhat less prevalent in the United States, affecting about 1 in 10 children here, which is about half the global rate. “But it’s a problem, and we wish it would go away, but before we know beyond a reasonable doubt what causes this condition, it’s going to be hard to stop it.”

Most cases of MH involve hypomineralization of the 6-year molars, the first adult molars to erupt, but the process starts at birth. “For 6-year molars, normal hardening of dental enamel takes place from the early postnatal period through infancy,” Dr. Hubbard said.

The 2-year and 12-year molars are affected about half as frequently as their 6-year counterparts, “so this extends the medical-risk window out to early school days, and slightly back to the perinatal period for the 12-year and 2-year molars, respectively,” he said.

A critical question is which childhood illnesses are most likely to set the stage for MH, he added. “Forty-plus years of epidemiology have failed to nail a specific cause or causal association. But given the high prevalence of MH – 20% in otherwise healthy kids – naturally we suspect some common illnesses are the culprits,” he said. “But which diseases, which medications, and which combinations?”

Dr. Hubbard’s advice to pediatricians is to be alert to MH: “If you’re inspecting a child’s throat, then why not look at their back teeth, too – particularly when they’re getting their new molars at 2, 6, and 12 years?”

The study was supported by the Melbourne Research Unit for Facial Disorders Department of Pharmacology & Therapeutics, Department of Paediatrics, and Faculty of Medicine, Dentistry, and Health Sciences at the University of Melbourne. The authors and Dr. Brofsky have disclosed no relevant financial relationships.

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

FROM FRONTIERS IN PHYSIOLOGY

Researchers have identified a potential cause of molar hypomineralization (MH), or “chalky teeth,” an underrecognized condition affecting one in five children worldwide. The discovery could lead to preventive medical therapies to reduce dental caries and extractions, they said.

According to a team led by biochemist Michael J. Hubbard, BDS, PhD, professor in the department of medicine, dentistry, and health sciences at the University of Melbourne, the “groundbreaking” research found that the failure of enamel to adequately harden is associated with exposure to serum albumin while teeth are developing. The blood protein “poisons” the growth of mineral crystals rather than injure the cells that deposit enamel, they reported.

The investigators, including researchers from Chile, said their findings hold promise for better clinical management of MH and open a new door into research on the broader pathogenesis and causes of the condition.

“We hope this breakthrough will eventually lead to medical prevention of MH, prompting global health benefits including major reductions in childhood tooth decay,” they wrote in an article published online Dec. 21 in Frontiers in Physiology.
 

More than cosmetic

Chalky teeth, characterized by discolored enamel spots, are not merely a cosmetic problem. The condition can lead to severe toothache, painful eating, tooth decay, and even abscesses and extractions. Although its triggers have eluded dental research for a century, Dr. Hubbard’s group said fossilized blood proteins such as albumin in the tooth appear to be at least one cause.

Biochemical evidence indicates that serum albumin surrounding developing teeth is normally excluded from enamel, Dr. Hubbard said in an interview. “Given that albumin binds strongly to hydroxyapatite-based mineral and blocks its growth, we infer that the epithelial barrier – the enamel-forming cells termed ameloblasts and normally responsible for excluding albumin – must break down in places in response to medical triggers.”

This breach enables localized infiltration of albumin, which then blocks further hardening of soft, immature enamel, leading to residual spots or patches of chalky enamel once the tooth eventually erupts into the mouth. “In other words, we infer that chalky enamel spots coincide with localized breaches of an epithelial barrier that are triggered by yet-to-be determined systemic insults,” he said.

Joseph Brofsky, DMD, section head of pediatric dentistry at North Shore LIJ Cohen Children’s Medical Center of New York, in Queens, agreed that that the definitive cause of MH has evaded identification for a hundred years. However, he expressed skepticism about the fossilized blood protein hypothesis.

“That’s a long shot. It’s a possibility, and I’m not ruling it out, but we’re not 100% sure,” said Dr. Brofsky, who was not involved in the research.

In his experience, MH is somewhat less prevalent in the United States, affecting about 1 in 10 children here, which is about half the global rate. “But it’s a problem, and we wish it would go away, but before we know beyond a reasonable doubt what causes this condition, it’s going to be hard to stop it.”

Most cases of MH involve hypomineralization of the 6-year molars, the first adult molars to erupt, but the process starts at birth. “For 6-year molars, normal hardening of dental enamel takes place from the early postnatal period through infancy,” Dr. Hubbard said.

The 2-year and 12-year molars are affected about half as frequently as their 6-year counterparts, “so this extends the medical-risk window out to early school days, and slightly back to the perinatal period for the 12-year and 2-year molars, respectively,” he said.

A critical question is which childhood illnesses are most likely to set the stage for MH, he added. “Forty-plus years of epidemiology have failed to nail a specific cause or causal association. But given the high prevalence of MH – 20% in otherwise healthy kids – naturally we suspect some common illnesses are the culprits,” he said. “But which diseases, which medications, and which combinations?”

Dr. Hubbard’s advice to pediatricians is to be alert to MH: “If you’re inspecting a child’s throat, then why not look at their back teeth, too – particularly when they’re getting their new molars at 2, 6, and 12 years?”

The study was supported by the Melbourne Research Unit for Facial Disorders Department of Pharmacology & Therapeutics, Department of Paediatrics, and Faculty of Medicine, Dentistry, and Health Sciences at the University of Melbourne. The authors and Dr. Brofsky have disclosed no relevant financial relationships.

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

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.

Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.

The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.

The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.

In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.

In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.

“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.

In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.

Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.

“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”

Feinstein Institutes for Medical Research

According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”

In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.

Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.

“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”

These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.

More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
 

The Centers for Medicare & Medicaid Services has finalized a rule to expand Medicare coverage to include continuous glucose monitoring (CGM) devices that are not approved for making treatment decisions.

Proposed in November 2020, the final CMS rule applies primarily to CGMs that integrate with Medtronic insulin pumps. Those CGMs have not been approved by the Food and Drug Administration to replace the need for fingerstick blood glucose measurements in determining insulin or other glucose-lowering medication dosing.

Other CGM systems, Dexcom G6 and Abbott Libre, have “therapeutic” indications and were already covered under Medicare, as was the combined insulin pump–CGM Tandem Diabetes Care Control-IQ technology system.

The expanded coverage means that people using the Medtronic 770G or 630G hybrid closed-loop insulin delivery systems will receive coverage for all the systems’ components, and that people aging into Medicare won’t lose any coverage for those devices.

Medtronic will continue to offer its CGM Access Discount to all Medicare customers until the ruling takes effect. The proposed rule was finalized on Dec. 21, 2021, and will be effective starting 60 days after official publication.

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

The Centers for Medicare & Medicaid Services has finalized a rule to expand Medicare coverage to include continuous glucose monitoring (CGM) devices that are not approved for making treatment decisions.

Proposed in November 2020, the final CMS rule applies primarily to CGMs that integrate with Medtronic insulin pumps. Those CGMs have not been approved by the Food and Drug Administration to replace the need for fingerstick blood glucose measurements in determining insulin or other glucose-lowering medication dosing.

Other CGM systems, Dexcom G6 and Abbott Libre, have “therapeutic” indications and were already covered under Medicare, as was the combined insulin pump–CGM Tandem Diabetes Care Control-IQ technology system.

The expanded coverage means that people using the Medtronic 770G or 630G hybrid closed-loop insulin delivery systems will receive coverage for all the systems’ components, and that people aging into Medicare won’t lose any coverage for those devices.

Medtronic will continue to offer its CGM Access Discount to all Medicare customers until the ruling takes effect. The proposed rule was finalized on Dec. 21, 2021, and will be effective starting 60 days after official publication.

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

The Centers for Medicare & Medicaid Services has finalized a rule to expand Medicare coverage to include continuous glucose monitoring (CGM) devices that are not approved for making treatment decisions.

Proposed in November 2020, the final CMS rule applies primarily to CGMs that integrate with Medtronic insulin pumps. Those CGMs have not been approved by the Food and Drug Administration to replace the need for fingerstick blood glucose measurements in determining insulin or other glucose-lowering medication dosing.

Other CGM systems, Dexcom G6 and Abbott Libre, have “therapeutic” indications and were already covered under Medicare, as was the combined insulin pump–CGM Tandem Diabetes Care Control-IQ technology system.

The expanded coverage means that people using the Medtronic 770G or 630G hybrid closed-loop insulin delivery systems will receive coverage for all the systems’ components, and that people aging into Medicare won’t lose any coverage for those devices.

Medtronic will continue to offer its CGM Access Discount to all Medicare customers until the ruling takes effect. The proposed rule was finalized on Dec. 21, 2021, and will be effective starting 60 days after official publication.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

Early interventions that focus on clinical case management and psychiatric care, and not necessarily on individual psychotherapy, are effective for young patients with borderline personality disorder (BPD), new research suggests.

Findings from the Monitoring Outcomes of Borderline Personality Disorder in Youth (MOBY) trial also showed improved psychosocial functioning and reduced suicide ideation with these therapies.

The results suggest that, contrary to common belief, psychotherapy is not the only effective approach for early BPD, lead author Andrew M. Chanen, PhD, director of clinical programs and services and head of personality disorder research at Orygen, Melbourne, told this news organization.

“We can say that early diagnosis and early treatment is effective, and the treatment doesn’t need to involve individual psychotherapy but does need to involve clinical case management and psychiatric care,” said Dr. Chanen, a professorial fellow at the Centre for Youth Mental Health, University of Melbourne.

The findings were published online in JAMA Psychiatry.
 

Extreme sensitivity

Patients with BPD have “extreme sensitivity to interpersonal slights” and often exhibit intense and volatile emotions and impulsive behavior, Dr. Chanen noted. Many will self-harm, abuse drugs, or attempt suicide; the suicide rate among patients with BPD is 8%-10%.

The condition is typically diagnosed in puberty or early adulthood, affecting about 3% of young people and a little more than 1% of adults.

Because of their aggression and interpersonal difficulties, patients with BPD are often discriminated against by health professionals and end up not getting treated, said Dr. Chanen.

Those who are treated often receive individual psychotherapy, such as dialectical behavior therapy (DBT). That type of therapy, which teaches healthy ways to cope with stress and regulate emotions, is very effective, Dr. Chanen said.

The MOBY trial examined three treatment approaches: the Helping Young People Early (HYPE) model, HYPE combined with weekly “befriending,” and a general youth mental health service (YMHS) model combined with befriending.

A key element of HYPE is cognitive analytic therapy, a psychotherapy program focused on understanding problematic self-management and interpersonal relationship patterns. The model includes clinical case management, such as attending to housing, vocational and educational issues, other mental health needs, and physical health needs.

In the second model, the psychotherapy of the HYPE program was replaced with befriending, which involves chatting with a patient about neutral topics such as sports and avoiding emotionally loaded topics such as interpersonal problems.

For YMHS plus befriending, experts trained in treating young people, but not specialized in treating BPD, were involved in managing patients.

‘High satisfaction’

Researchers randomly assigned 139 participants aged 15-25 years (80.6% women; mean age, 19.1 years) with BPD to one of the treatment arms. Of these, 128 (92.1%) were included in the intent-to-treat analysis.

The primary endpoint was psychosocial functioning, as measured by the Inventory of Interpersonal Problems Circumplex Version and the Social Adjustment Scale–Self-Report. Secondary endpoints included suicidal ideation, suicide attempts, nonsuicidal self-injury, depression, substance use, and treatment satisfaction.

The investigators reported group averages, but the study’s noninferiority design did not allow for determining if one treatment had superior efficacy.

All groups improved significantly on the primary endpoint. At 12 months, there was a mean 28.91-point (23.8%) drop in interpersonal problems and a mean 0.55-point (19.3%) drop in social adjustment scores.

For secondary outcomes, mean improvements at 12 months ranged from 40.7% (17.64 points) on the depression scale to 52.7% (6.22 points) for suicide ideation.

“The only area where the treatment didn’t really have an impact was substance use,” said Dr. Chanen. “Satisfaction was high for all three interventions throughout the study, and it’s hard to improve on high satisfaction.”

‘Turns things upside down’

That patients across all groups had marked and sustained improvements “in ways you wouldn’t expect for BPD” supports the conclusion that the interventions had a true effect, Dr. Chanen said.

The results suggest early diagnosis and “a not very complicated treatment [will] drastically improve the lives of these young people,” he added.

They also imply there are effective alternatives to psychotherapy, which many individuals in the field insist is the only way to treat BPD. “This study turns things upside down and says actually it’s not. It’s the basics of treatment that are important,” Dr. Chanen said.

When a patient presents at the emergency department following a severe overdose, “it’s a reflex” for clinicians to refer that person to a psychotherapy program. “The problem is, these programs are not plentiful enough to be able to service the needs of this group,” Dr. Chanen noted.

On the other hand, the skills for clinical case management and psychiatric care “are available throughout the mental health systems,” he added.

The researchers are planning another analysis to determine whether age and sex predict better outcomes in these patients with BPD.
 

Unique contribution

Commenting for this news organization, John M. Oldham, MD, distinguished emeritus professor, Baylor College of Medicine, Houston, said a “unique and important contribution” of the study is the focus on early intervention.

“The general standard approach in psychiatry and the diagnostic world has been to not even consider anything until after somebody is 18 years of age, which is a mistake because these kids can become quite impaired earlier than that,” he said.

Dr. Oldham, who was not involved with the research, chaired the American Psychiatric Association workgroup that developed the 2001 evidence-based practice guideline for treating BPD, which recommended psychotherapy as the primary treatment. The guideline was last updated in 2005 – and another update is currently being developed, he noted.

There is an emerging trend toward “good psychiatric management” that focuses on level of functioning rather than on a specific strategy requiring a certificate of training that “not many people out there have,” said Dr. Oldham.

“You’re not going to make much headway with these kids if you’re going to be searching around for a DBT-certified therapist. What you need is to bring them in, get them to trust you, and in a sense be a kind of overall behavioral medicine navigator for them,” he added.

Dr. Oldham noted that, although the primary study outcome improved between 19% and 24%, “that means three-quarters of the people didn’t improve.”

He also pointed out this was only a 1-year trial. “Sometimes treatment for people with a personality disorder such as borderline takes a lot longer than that,” Dr. Oldham concluded.

The trial was funded by the National Health and Medical Research Council. Dr. Chanen reports receiving grants from the Australian government’s National Health and Medical Research Council during the conduct of the study and other support from the Helping Young People Early (HYPE) translational program outside the submitted work. He and another investigator cofounded and lead the HYPE clinical program, a government-funded program with continuous support, and the HYPE translational program, a not-for-profit training program. Dr. Oldham reported no relevant financial relationships.

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

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Pregnant women who are at risk of preeclampsia can now be identified early before symptoms develop, finds new research from Kings College London and Guy’s and St Thomas’ NHS Foundation Trust, published in Nature.

The study, supported by the National Institute for Health Research and in partnership with the Mirvie RNA platform, analyzed the genetic material from over 2,500 blood samples of pregnant women from eight independent cohorts with multiple demographics, including socioeconomic background, geographic location, ethnicity, and nationality, collected 14.5 weeks before delivery.

“Because the study drew upon samples for a diverse group of women, including participants recruited across King’s Health Partners, the molecular signature is very reliable and has potential to outperform currently available tests,” said Rachel Tribe, PhD, department of women and children’s health, King’s College London.

Researchers used plasma cell-free RNA (cfRNA) transcripts to examine the standard molecular mechanism between the fetus, maternal, and placental tissues in order to determine fetal development and healthy pregnancy progression. Deviation from the standard cfRNA expression was also observed to establish the molecular pathway for those at risk of preeclampsia before clinical presentation.

A cfRNA signal from a single blood sample showed a 32.3% positive-predictive value and 75% sensitivity, which exceeds current positive-predictive values from recent clinical state-of-the-art models.

In addition, 73% of participants with a positive-predictive value were identified “as destined to have a medically indicated preterm birth over 3 months in advance of the preeclampsia symptoms,” said the authors.

With up to 1 in 12 pregnancies affected by preeclampsia, and the diagnosis most often only being made in the third trimester, these results provide a promising outlook for pregnant women “so that they can be more closely monitored and treated by the clinicians involved,” commented Dr. Tribe.

“We are now focused on ongoing clinical research to further validate these results and improve the understanding of other pregnancy complications,” she said. “As a scientist, it was also extremely interesting to see that the molecular signature tells us something about mechanisms associated with health in pregnancy and complications including preeclampsia; such knowledge will aid development of treatment strategies in the future.”

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

Best of 2021
The RA Report

A Supplement to Rhematology News

Contents: 

• Treatment responders show unique differences in gut microbiome
• Gene variant confirmed as strong predictor of interstitial lung disease
• Multiple comorbidities lower odds of disease control
• Blood-based test aims to predict nonresponse to TNF inhibitors
• Evidence grows for food as treatment
• Oral steroids plus proton pump inhibitors raise osteoporotic fracture risk
• Novel study links air pollution to increased risk of flares

Best of 2021
The RA Report

A Supplement to Rhematology News

Contents: 

• Treatment responders show unique differences in gut microbiome
• Gene variant confirmed as strong predictor of interstitial lung disease
• Multiple comorbidities lower odds of disease control
• Blood-based test aims to predict nonresponse to TNF inhibitors
• Evidence grows for food as treatment
• Oral steroids plus proton pump inhibitors raise osteoporotic fracture risk
• Novel study links air pollution to increased risk of flares

Best of 2021
The RA Report

A Supplement to Rhematology News

Contents: 

• Treatment responders show unique differences in gut microbiome
• Gene variant confirmed as strong predictor of interstitial lung disease
• Multiple comorbidities lower odds of disease control
• Blood-based test aims to predict nonresponse to TNF inhibitors
• Evidence grows for food as treatment
• Oral steroids plus proton pump inhibitors raise osteoporotic fracture risk
• Novel study links air pollution to increased risk of flares

With a majority-minority population expected in the United States by 2044, improving diversity and cultural competency in the dermatology workforce is now more important than ever. A more diverse workforce increases the cultural competence of all providers, provides greater opportunities for mentorship and sponsorship of underrepresented minority (URM) trainees, establishes a more inclusive environment for learners, and enhances the knowledge and productivity of the workforce.^1-3 Additionally, it is imperative to address clinical care disparities seen in minority patients in dermatology, including treatment of skin cancer, psoriasis, acne, atopic dermatitis, and other diseases.^4-7

Despite the attention that has been devoted to improving diversity in medicine,^8-10 dermatology remains one of the least diverse specialties, prompting additional calls to action within the field.¹¹ Why does the lack of diversity still exist in dermatology, and what is the path to correcting this problem? In this article, we review the evidence of diversity barriers at different stages of medical education training that may impede academic advancement for minority learners pursuing careers in dermatology.

Undergraduate Medical Education

The term leaky pipeline refers to the progressive decline in the number of URMs along a given career path, including in dermatology. The Association of American Medical Colleges defines URMs as racial/ethnic populations that are “underrepresented in the medical profession relative to their numbers in the general population.”⁹ The first leak in the pipeline is that URMs are not applying to medical school. From 2002 and 2017, rates of both application and matriculation to medical school were lower by 30% to 70% in URM groups compared to White students, including Hispanic, Black, and American Indian/Alaska Native students.^12,13 The decision not to apply to medical school was greater in URM undergraduate students irrespective of scholastic ability as measured by SAT scores.¹⁴

A striking statistic is that the number of Black men matriculating into medical school in 2014 was less than it was in 1978 despite the increase in the number of US medical schools and efforts to recruit more diverse student populations. The Association of American Medical Colleges identified potential reasons for this decline, including poor early education, lack of mentorship, negative perceptions of Black men due to racial stereotypes, and lack of financial and academic resources to support the application process.^8,13,15-17 Implicit racial bias by admission committees also may play a role.

Medical School Matriculation and Applying to Dermatology Residency

There is greater representation of URM students in medical school than in dermatology residency, which means URM students are either not applying to dermatology programs or they are not matching into the specialty. In the Electronic Residency Application Service’s 2016-2017 application cycle (N=776), there were 76 (9.8%) URM dermatology residency applicants.¹⁸ In 2018, there was a notable decline in representation of Black students among residency applicants (4.9%) to matched residents (3.7%), and there were only 133 (9.3%) URM dermatology residents in total (PGY2-PGY4 classes).¹⁹ The lack of exposure to medical subspecialties and the recommendation by medical schools for URM medical students to pursue careers in primary care have been cited as reasons that these students may not apply to residency programs in specialty care.^20,21 The presence of an Accreditation Council for Graduate Medical Education dermatology residency program, fellowships, and dermatology interest groups at their medical schools correlated with higher proportions of URM students applying to dermatology programs.²⁰

Underrepresented minority students face critical challenges during medical school, including receiving lower grades in both standardized and school-designated assessments and clerkship grades.^21,22 A 2019 National Board of Medical Examiners study found that Hispanic and Black test takers scored 12.1 and 16.6 points lower than White men, respectively, on the US Medical Licensing Examination (USMLE) Step 1.²³ Black and Asian students also were less likely than White students to be selected as members of the Alpha Omega Alpha Honor Medical Society (AΩA), even after accounting for USMLE Step 1 scores, research productivity, community service, leadership, and Gold Humanism Honor Society membership.²⁴ Taken together, the emphasis on clinical grades, USMLE scores, and AΩA status as recruitment and selection criteria likely deters URM students from applying to and may preclude them from successfully matching into highly selective specialties such as dermatology.²⁵

A recent cross-sectional study showed that lack of equitable resources, lack of support, financial constrictions, and lack of group identity were 4 barriers to URM students matching into dermatology.²⁶ Dermatology is a competitive specialty with the highest median Electronic Residency Application Service applications submitted per US applicant (n=90)²⁷ and an approximate total cost per US applicant of $10,781.^28,29 Disadvantaged URM applicants noted relying on loans while non-URM applicants cited family financial support as being beneficial.²⁶ In addition, an increasing number of applicants take gap years for research, which pose additional costs for finances and resources. In contrast, mentorship and participation in pipeline/enrichment programs were factors associated with URM students matching into dermatology.²⁶

Similar to the transition from medical school into dermatology residency, URM dermatology residents are either not applying to fellowships or are not getting in. In the 2018-2019 academic year, there were no Black, Hispanic, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native Mohs micrographic surgery and dermatologic oncology fellows.¹⁹ Similarly, there were no Black, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native dermatopathology fellows. There were 4 (6%) Hispanic dermatopathology fellows.¹⁹

There also is marked underrepresentation of minority groups—and minimal growth over time—in the dermatology procedural subspecialty. Whereas the percentage of female Mohs surgeons increased considerably from 1985 to 2005 (12.7% to 40.9%, respectively), the percentage of URM Mohs surgeons remained steady from 4.2% to 4.6%, respectively, and remained at 4.5% in 2014.³⁰

There are no available data on the race/ethnicity of fellowship applicants, as these demographic data for the application process have not been consistently or traditionally collected. The reasons why there are so few URM dermatology fellows is not known; whether this is due to a lack of mentorship or whether other factors lead to residents not applying for advanced training needs further study. Financial factors related to prolonged training, which include lower salaries and delayed loan repayment, may present barriers to applying to fellowships.

Lack of URM Academic Faculty in Dermatology

At the academic faculty level, URM representation continues to worsen. Lett et al³¹ found that there is declining racial and ethnic representation in clinical academic medicine relative to US census data for 16 US medical specialties, including dermatology, with growing underrepresentation of Black and Hispanic faculty at the associate professor and full professor levels and underrepresentation in all faculty ranks. From 1970 to 2018, URM faculty in dermatology only increased from 4.8% to 7.4%, respectively. Non-URM female and male faculty members increased by 13.8 and 10.8 faculty members per year, respectively, while URM female and male faculty members increased by 1.2 and 0.8 faculty members per year, respectively.³²

Underrepresentation of minorities seen in dermatology faculty may result from clinical demands, minority taxation (defined as the extensive service requirements uniquely experienced by URM faculty to disproportionately serve as representatives on academic committees and to mentor URM students), and barriers to academic promotion, which are challenges uniquely encountered by URMs in academic dermatology.³³ Increased clinical demand may result from the fact that URM physicians are more likely to care for underserved populations, those of lower socioeconomic status, non-English–speaking patients, those on Medicaid, and those who are uninsured, which may impact renumeration. Minority tax experienced by URM faculty includes mentoring URM medical students, providing cultural expertise to departments and institutions, and participating in community service projects and outreach programs. Specifically, many institutional committees require the participation of a URM member, resulting in URM faculty members experiencing higher committee service burden. Many, if not all, of these responsibilities often are not compensated through salary or academic promotion.

A Call to Action

There are several steps that can be taken to create a pathway to dermatology that is inclusive, flexible, and supportive of URMs.

• Increase early exposure to dermatology in medical school. Early exposure and mentorship opportunities are associated with higher rates of students pursuing specialty field careers.³⁴ Increased early opportunities allow for URM students to consider and explore a career in dermatology; receive mentorship; and ensure that dermatology, including topics related to skin of color (SOC), is incorporated into their learning. The American Academy of Dermatology has contributed to these efforts by its presence at every national meeting of the Student National Medical Association and Latino Medical Student Association, as well as its involvement with Nth Dimensions, which offers various educational opportunities for URM medical students.

• Implement equitable grading and holistic review processes in medical school. Racial/ethnic differences in clinical grading and standardized test scores in medical school demonstrate why holistic review of dermatology residency applicants is needed and why other metrics such as USMLE scores and AΩA status should be de-emphasized or eliminated when evaluating candidates. To support equity, many medical schools have eliminated honors grading, and some schools have eliminated AΩA distinction.

• Increase diversity of dermatology residents and residency programs. Implicit bias training for a medical school admissions committee has been shown to increase diversity in medical school enrollment.³⁵ Whether implicit bias training and other diversity training may benefit dermatology residency selection must be examined, including study of unintended consequences, such as reduced diversity, increased microaggressions toward minority colleagues, and the illusion of fairness.^36-39 Increasing representation is not sufficient—creating inclusive residency training environments is a critical parallel aim. Prioritizing diversity in dermatology residency recruitment is imperative. Creating dermatology residency positions specifically for URM residents may be an important option, as done at the University of Pennsylvania (Philadelphia, Pennsylvania) and Duke University (Durham, North Carolina).

• Create effective programs for URM mentorship. Due to the competitive nature of dermatology residency, the need for mentors in dermatology is critically vital for URM medical students, especially those without a home dermatology program at their medical school. Further development of formal mentorship and pipeline programs is essential at both the local and national levels. Some national examples of these initiatives include diversity mentorship programs offered by the American Academy of Dermatology, Skin of Color Society, Women’s Dermatologic Society, and Student National Medical Association. Many institutional programs also offer invaluable opportunities, such as the summer research fellowship at the University of California, San Francisco (UCSF); visiting clerkship grants for URMs at the University of Pennsylvania (Philadelphia, Pennsylvania) and Johns Hopkins University (Baltimore, Maryland); and integrated programs, such as the Visiting Elective Scholarship Program at UCSF, which provides funding and faculty mentorship for URM students completing an away rotation at UCSF.

• Establish longitudinal skin-of-color curricula and increased opportunities for research. More robust SOC training may lead to an increasingly diverse workforce. It is important that medical student and dermatology resident and fellow education include training on SOC to ensure high-quality care to diverse patient populations, which also may enhance the knowledge of trainees, encourage clinical and research interest in this field, and reduce health care disparities. Increasing research opportunities and offering formalized longitudinal training in SOC as well as incorporating more diverse images in medical school education may foster greater interest in this field at a time when trainees are establishing their career interests. At present, there is considerable room for improvement. Nijhawan et al⁴⁰ surveyed 63 dermatology chief residents and 41 program directors and found only 14.3% and 14.6%, respectively, reported having an expert who conducts clinic specializing in SOC. Only 52.4% and 65.9% reported having didactic sessions or lectures focused on SOC diseases, and 30.2% and 12.2% reported having a dedicated rotation for residents to gain experience in SOC.⁴⁰ A more recent study showed that when faculty were asked to incorporate more SOC content into lectures, the most commonly identified barrier to implementation was a lack of SOC images.⁴¹ Additionally, there remains a paucity of published research on this topic, with SOC articles representing only 2.7% of the literature.⁴² These numbers demonstrate the continued need for a more inclusive and comprehensive curriculum in dermatology residency programs and more robust funding for SOC research.

• Recruit and support URM faculty. Increasing diversity in dermatology residency programs likely will increase the number of potential URMs pursuing additional fellowship training and academic dermatology with active career mentorship and support. In addition, promoting faculty retention by combatting the progressive loss of URMs at all faculty levels is paramount. Mentorship for URM physicians has been shown to play a key role in the decision to pursue academic medicine as well as academic productivity and job satisfaction.^43,44 The visibility, cultural competency, clinical work, academic productivity, and mentorship efforts that URM faculty provide are essential to enhancing patient care, teaching diverse groups of learners, and recruiting more diverse trainees. Protected time to participate in professional development opportunities has been shown to improve recruitment and retention of URM faculty and offer additional opportunities for junior faculty to find mentors.^35,36 Incentivizing clinical care of underserved populations also may augment financial stability for URM physicians who choose to care for these patients. Finally, diversity work and community service should be legitimized and count toward faculty promotion.

Conclusion

There are numerous factors that contribute to the leaky pipeline in dermatology (eFigure). Many challenges that are unique to the URM population disadvantage these students from entering medical school, applying to dermatology residency, matching into dermatology fellowships, pursuing and staying in faculty positions, and achieving faculty advancement into leadership positions. With each progressive step along this trajectory, there is less minority representation. All dermatologists, regardless of race/ethnicity, need to play an active role and must prioritize diversity, equity, and inclusion efforts at all levels of education and training for the betterment of the specialty.

With a majority-minority population expected in the United States by 2044, improving diversity and cultural competency in the dermatology workforce is now more important than ever. A more diverse workforce increases the cultural competence of all providers, provides greater opportunities for mentorship and sponsorship of underrepresented minority (URM) trainees, establishes a more inclusive environment for learners, and enhances the knowledge and productivity of the workforce.^1-3 Additionally, it is imperative to address clinical care disparities seen in minority patients in dermatology, including treatment of skin cancer, psoriasis, acne, atopic dermatitis, and other diseases.^4-7

Despite the attention that has been devoted to improving diversity in medicine,^8-10 dermatology remains one of the least diverse specialties, prompting additional calls to action within the field.¹¹ Why does the lack of diversity still exist in dermatology, and what is the path to correcting this problem? In this article, we review the evidence of diversity barriers at different stages of medical education training that may impede academic advancement for minority learners pursuing careers in dermatology.

Undergraduate Medical Education

The term leaky pipeline refers to the progressive decline in the number of URMs along a given career path, including in dermatology. The Association of American Medical Colleges defines URMs as racial/ethnic populations that are “underrepresented in the medical profession relative to their numbers in the general population.”⁹ The first leak in the pipeline is that URMs are not applying to medical school. From 2002 and 2017, rates of both application and matriculation to medical school were lower by 30% to 70% in URM groups compared to White students, including Hispanic, Black, and American Indian/Alaska Native students.^12,13 The decision not to apply to medical school was greater in URM undergraduate students irrespective of scholastic ability as measured by SAT scores.¹⁴

A striking statistic is that the number of Black men matriculating into medical school in 2014 was less than it was in 1978 despite the increase in the number of US medical schools and efforts to recruit more diverse student populations. The Association of American Medical Colleges identified potential reasons for this decline, including poor early education, lack of mentorship, negative perceptions of Black men due to racial stereotypes, and lack of financial and academic resources to support the application process.^8,13,15-17 Implicit racial bias by admission committees also may play a role.

Medical School Matriculation and Applying to Dermatology Residency

There is greater representation of URM students in medical school than in dermatology residency, which means URM students are either not applying to dermatology programs or they are not matching into the specialty. In the Electronic Residency Application Service’s 2016-2017 application cycle (N=776), there were 76 (9.8%) URM dermatology residency applicants.¹⁸ In 2018, there was a notable decline in representation of Black students among residency applicants (4.9%) to matched residents (3.7%), and there were only 133 (9.3%) URM dermatology residents in total (PGY2-PGY4 classes).¹⁹ The lack of exposure to medical subspecialties and the recommendation by medical schools for URM medical students to pursue careers in primary care have been cited as reasons that these students may not apply to residency programs in specialty care.^20,21 The presence of an Accreditation Council for Graduate Medical Education dermatology residency program, fellowships, and dermatology interest groups at their medical schools correlated with higher proportions of URM students applying to dermatology programs.²⁰

Underrepresented minority students face critical challenges during medical school, including receiving lower grades in both standardized and school-designated assessments and clerkship grades.^21,22 A 2019 National Board of Medical Examiners study found that Hispanic and Black test takers scored 12.1 and 16.6 points lower than White men, respectively, on the US Medical Licensing Examination (USMLE) Step 1.²³ Black and Asian students also were less likely than White students to be selected as members of the Alpha Omega Alpha Honor Medical Society (AΩA), even after accounting for USMLE Step 1 scores, research productivity, community service, leadership, and Gold Humanism Honor Society membership.²⁴ Taken together, the emphasis on clinical grades, USMLE scores, and AΩA status as recruitment and selection criteria likely deters URM students from applying to and may preclude them from successfully matching into highly selective specialties such as dermatology.²⁵

A recent cross-sectional study showed that lack of equitable resources, lack of support, financial constrictions, and lack of group identity were 4 barriers to URM students matching into dermatology.²⁶ Dermatology is a competitive specialty with the highest median Electronic Residency Application Service applications submitted per US applicant (n=90)²⁷ and an approximate total cost per US applicant of $10,781.^28,29 Disadvantaged URM applicants noted relying on loans while non-URM applicants cited family financial support as being beneficial.²⁶ In addition, an increasing number of applicants take gap years for research, which pose additional costs for finances and resources. In contrast, mentorship and participation in pipeline/enrichment programs were factors associated with URM students matching into dermatology.²⁶

Similar to the transition from medical school into dermatology residency, URM dermatology residents are either not applying to fellowships or are not getting in. In the 2018-2019 academic year, there were no Black, Hispanic, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native Mohs micrographic surgery and dermatologic oncology fellows.¹⁹ Similarly, there were no Black, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native dermatopathology fellows. There were 4 (6%) Hispanic dermatopathology fellows.¹⁹

There also is marked underrepresentation of minority groups—and minimal growth over time—in the dermatology procedural subspecialty. Whereas the percentage of female Mohs surgeons increased considerably from 1985 to 2005 (12.7% to 40.9%, respectively), the percentage of URM Mohs surgeons remained steady from 4.2% to 4.6%, respectively, and remained at 4.5% in 2014.³⁰

There are no available data on the race/ethnicity of fellowship applicants, as these demographic data for the application process have not been consistently or traditionally collected. The reasons why there are so few URM dermatology fellows is not known; whether this is due to a lack of mentorship or whether other factors lead to residents not applying for advanced training needs further study. Financial factors related to prolonged training, which include lower salaries and delayed loan repayment, may present barriers to applying to fellowships.

Lack of URM Academic Faculty in Dermatology

At the academic faculty level, URM representation continues to worsen. Lett et al³¹ found that there is declining racial and ethnic representation in clinical academic medicine relative to US census data for 16 US medical specialties, including dermatology, with growing underrepresentation of Black and Hispanic faculty at the associate professor and full professor levels and underrepresentation in all faculty ranks. From 1970 to 2018, URM faculty in dermatology only increased from 4.8% to 7.4%, respectively. Non-URM female and male faculty members increased by 13.8 and 10.8 faculty members per year, respectively, while URM female and male faculty members increased by 1.2 and 0.8 faculty members per year, respectively.³²

Underrepresentation of minorities seen in dermatology faculty may result from clinical demands, minority taxation (defined as the extensive service requirements uniquely experienced by URM faculty to disproportionately serve as representatives on academic committees and to mentor URM students), and barriers to academic promotion, which are challenges uniquely encountered by URMs in academic dermatology.³³ Increased clinical demand may result from the fact that URM physicians are more likely to care for underserved populations, those of lower socioeconomic status, non-English–speaking patients, those on Medicaid, and those who are uninsured, which may impact renumeration. Minority tax experienced by URM faculty includes mentoring URM medical students, providing cultural expertise to departments and institutions, and participating in community service projects and outreach programs. Specifically, many institutional committees require the participation of a URM member, resulting in URM faculty members experiencing higher committee service burden. Many, if not all, of these responsibilities often are not compensated through salary or academic promotion.

A Call to Action

There are several steps that can be taken to create a pathway to dermatology that is inclusive, flexible, and supportive of URMs.

• Increase early exposure to dermatology in medical school. Early exposure and mentorship opportunities are associated with higher rates of students pursuing specialty field careers.³⁴ Increased early opportunities allow for URM students to consider and explore a career in dermatology; receive mentorship; and ensure that dermatology, including topics related to skin of color (SOC), is incorporated into their learning. The American Academy of Dermatology has contributed to these efforts by its presence at every national meeting of the Student National Medical Association and Latino Medical Student Association, as well as its involvement with Nth Dimensions, which offers various educational opportunities for URM medical students.

• Implement equitable grading and holistic review processes in medical school. Racial/ethnic differences in clinical grading and standardized test scores in medical school demonstrate why holistic review of dermatology residency applicants is needed and why other metrics such as USMLE scores and AΩA status should be de-emphasized or eliminated when evaluating candidates. To support equity, many medical schools have eliminated honors grading, and some schools have eliminated AΩA distinction.

• Increase diversity of dermatology residents and residency programs. Implicit bias training for a medical school admissions committee has been shown to increase diversity in medical school enrollment.³⁵ Whether implicit bias training and other diversity training may benefit dermatology residency selection must be examined, including study of unintended consequences, such as reduced diversity, increased microaggressions toward minority colleagues, and the illusion of fairness.^36-39 Increasing representation is not sufficient—creating inclusive residency training environments is a critical parallel aim. Prioritizing diversity in dermatology residency recruitment is imperative. Creating dermatology residency positions specifically for URM residents may be an important option, as done at the University of Pennsylvania (Philadelphia, Pennsylvania) and Duke University (Durham, North Carolina).

• Create effective programs for URM mentorship. Due to the competitive nature of dermatology residency, the need for mentors in dermatology is critically vital for URM medical students, especially those without a home dermatology program at their medical school. Further development of formal mentorship and pipeline programs is essential at both the local and national levels. Some national examples of these initiatives include diversity mentorship programs offered by the American Academy of Dermatology, Skin of Color Society, Women’s Dermatologic Society, and Student National Medical Association. Many institutional programs also offer invaluable opportunities, such as the summer research fellowship at the University of California, San Francisco (UCSF); visiting clerkship grants for URMs at the University of Pennsylvania (Philadelphia, Pennsylvania) and Johns Hopkins University (Baltimore, Maryland); and integrated programs, such as the Visiting Elective Scholarship Program at UCSF, which provides funding and faculty mentorship for URM students completing an away rotation at UCSF.

• Establish longitudinal skin-of-color curricula and increased opportunities for research. More robust SOC training may lead to an increasingly diverse workforce. It is important that medical student and dermatology resident and fellow education include training on SOC to ensure high-quality care to diverse patient populations, which also may enhance the knowledge of trainees, encourage clinical and research interest in this field, and reduce health care disparities. Increasing research opportunities and offering formalized longitudinal training in SOC as well as incorporating more diverse images in medical school education may foster greater interest in this field at a time when trainees are establishing their career interests. At present, there is considerable room for improvement. Nijhawan et al⁴⁰ surveyed 63 dermatology chief residents and 41 program directors and found only 14.3% and 14.6%, respectively, reported having an expert who conducts clinic specializing in SOC. Only 52.4% and 65.9% reported having didactic sessions or lectures focused on SOC diseases, and 30.2% and 12.2% reported having a dedicated rotation for residents to gain experience in SOC.⁴⁰ A more recent study showed that when faculty were asked to incorporate more SOC content into lectures, the most commonly identified barrier to implementation was a lack of SOC images.⁴¹ Additionally, there remains a paucity of published research on this topic, with SOC articles representing only 2.7% of the literature.⁴² These numbers demonstrate the continued need for a more inclusive and comprehensive curriculum in dermatology residency programs and more robust funding for SOC research.

• Recruit and support URM faculty. Increasing diversity in dermatology residency programs likely will increase the number of potential URMs pursuing additional fellowship training and academic dermatology with active career mentorship and support. In addition, promoting faculty retention by combatting the progressive loss of URMs at all faculty levels is paramount. Mentorship for URM physicians has been shown to play a key role in the decision to pursue academic medicine as well as academic productivity and job satisfaction.^43,44 The visibility, cultural competency, clinical work, academic productivity, and mentorship efforts that URM faculty provide are essential to enhancing patient care, teaching diverse groups of learners, and recruiting more diverse trainees. Protected time to participate in professional development opportunities has been shown to improve recruitment and retention of URM faculty and offer additional opportunities for junior faculty to find mentors.^35,36 Incentivizing clinical care of underserved populations also may augment financial stability for URM physicians who choose to care for these patients. Finally, diversity work and community service should be legitimized and count toward faculty promotion.

Conclusion

There are numerous factors that contribute to the leaky pipeline in dermatology (eFigure). Many challenges that are unique to the URM population disadvantage these students from entering medical school, applying to dermatology residency, matching into dermatology fellowships, pursuing and staying in faculty positions, and achieving faculty advancement into leadership positions. With each progressive step along this trajectory, there is less minority representation. All dermatologists, regardless of race/ethnicity, need to play an active role and must prioritize diversity, equity, and inclusion efforts at all levels of education and training for the betterment of the specialty.

With a majority-minority population expected in the United States by 2044, improving diversity and cultural competency in the dermatology workforce is now more important than ever. A more diverse workforce increases the cultural competence of all providers, provides greater opportunities for mentorship and sponsorship of underrepresented minority (URM) trainees, establishes a more inclusive environment for learners, and enhances the knowledge and productivity of the workforce.^1-3 Additionally, it is imperative to address clinical care disparities seen in minority patients in dermatology, including treatment of skin cancer, psoriasis, acne, atopic dermatitis, and other diseases.^4-7

Despite the attention that has been devoted to improving diversity in medicine,^8-10 dermatology remains one of the least diverse specialties, prompting additional calls to action within the field.¹¹ Why does the lack of diversity still exist in dermatology, and what is the path to correcting this problem? In this article, we review the evidence of diversity barriers at different stages of medical education training that may impede academic advancement for minority learners pursuing careers in dermatology.

Undergraduate Medical Education

The term leaky pipeline refers to the progressive decline in the number of URMs along a given career path, including in dermatology. The Association of American Medical Colleges defines URMs as racial/ethnic populations that are “underrepresented in the medical profession relative to their numbers in the general population.”⁹ The first leak in the pipeline is that URMs are not applying to medical school. From 2002 and 2017, rates of both application and matriculation to medical school were lower by 30% to 70% in URM groups compared to White students, including Hispanic, Black, and American Indian/Alaska Native students.^12,13 The decision not to apply to medical school was greater in URM undergraduate students irrespective of scholastic ability as measured by SAT scores.¹⁴

A striking statistic is that the number of Black men matriculating into medical school in 2014 was less than it was in 1978 despite the increase in the number of US medical schools and efforts to recruit more diverse student populations. The Association of American Medical Colleges identified potential reasons for this decline, including poor early education, lack of mentorship, negative perceptions of Black men due to racial stereotypes, and lack of financial and academic resources to support the application process.^8,13,15-17 Implicit racial bias by admission committees also may play a role.

Medical School Matriculation and Applying to Dermatology Residency

There is greater representation of URM students in medical school than in dermatology residency, which means URM students are either not applying to dermatology programs or they are not matching into the specialty. In the Electronic Residency Application Service’s 2016-2017 application cycle (N=776), there were 76 (9.8%) URM dermatology residency applicants.¹⁸ In 2018, there was a notable decline in representation of Black students among residency applicants (4.9%) to matched residents (3.7%), and there were only 133 (9.3%) URM dermatology residents in total (PGY2-PGY4 classes).¹⁹ The lack of exposure to medical subspecialties and the recommendation by medical schools for URM medical students to pursue careers in primary care have been cited as reasons that these students may not apply to residency programs in specialty care.^20,21 The presence of an Accreditation Council for Graduate Medical Education dermatology residency program, fellowships, and dermatology interest groups at their medical schools correlated with higher proportions of URM students applying to dermatology programs.²⁰

Underrepresented minority students face critical challenges during medical school, including receiving lower grades in both standardized and school-designated assessments and clerkship grades.^21,22 A 2019 National Board of Medical Examiners study found that Hispanic and Black test takers scored 12.1 and 16.6 points lower than White men, respectively, on the US Medical Licensing Examination (USMLE) Step 1.²³ Black and Asian students also were less likely than White students to be selected as members of the Alpha Omega Alpha Honor Medical Society (AΩA), even after accounting for USMLE Step 1 scores, research productivity, community service, leadership, and Gold Humanism Honor Society membership.²⁴ Taken together, the emphasis on clinical grades, USMLE scores, and AΩA status as recruitment and selection criteria likely deters URM students from applying to and may preclude them from successfully matching into highly selective specialties such as dermatology.²⁵

A recent cross-sectional study showed that lack of equitable resources, lack of support, financial constrictions, and lack of group identity were 4 barriers to URM students matching into dermatology.²⁶ Dermatology is a competitive specialty with the highest median Electronic Residency Application Service applications submitted per US applicant (n=90)²⁷ and an approximate total cost per US applicant of $10,781.^28,29 Disadvantaged URM applicants noted relying on loans while non-URM applicants cited family financial support as being beneficial.²⁶ In addition, an increasing number of applicants take gap years for research, which pose additional costs for finances and resources. In contrast, mentorship and participation in pipeline/enrichment programs were factors associated with URM students matching into dermatology.²⁶

Similar to the transition from medical school into dermatology residency, URM dermatology residents are either not applying to fellowships or are not getting in. In the 2018-2019 academic year, there were no Black, Hispanic, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native Mohs micrographic surgery and dermatologic oncology fellows.¹⁹ Similarly, there were no Black, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native dermatopathology fellows. There were 4 (6%) Hispanic dermatopathology fellows.¹⁹

There also is marked underrepresentation of minority groups—and minimal growth over time—in the dermatology procedural subspecialty. Whereas the percentage of female Mohs surgeons increased considerably from 1985 to 2005 (12.7% to 40.9%, respectively), the percentage of URM Mohs surgeons remained steady from 4.2% to 4.6%, respectively, and remained at 4.5% in 2014.³⁰

There are no available data on the race/ethnicity of fellowship applicants, as these demographic data for the application process have not been consistently or traditionally collected. The reasons why there are so few URM dermatology fellows is not known; whether this is due to a lack of mentorship or whether other factors lead to residents not applying for advanced training needs further study. Financial factors related to prolonged training, which include lower salaries and delayed loan repayment, may present barriers to applying to fellowships.

Lack of URM Academic Faculty in Dermatology

At the academic faculty level, URM representation continues to worsen. Lett et al³¹ found that there is declining racial and ethnic representation in clinical academic medicine relative to US census data for 16 US medical specialties, including dermatology, with growing underrepresentation of Black and Hispanic faculty at the associate professor and full professor levels and underrepresentation in all faculty ranks. From 1970 to 2018, URM faculty in dermatology only increased from 4.8% to 7.4%, respectively. Non-URM female and male faculty members increased by 13.8 and 10.8 faculty members per year, respectively, while URM female and male faculty members increased by 1.2 and 0.8 faculty members per year, respectively.³²

Underrepresentation of minorities seen in dermatology faculty may result from clinical demands, minority taxation (defined as the extensive service requirements uniquely experienced by URM faculty to disproportionately serve as representatives on academic committees and to mentor URM students), and barriers to academic promotion, which are challenges uniquely encountered by URMs in academic dermatology.³³ Increased clinical demand may result from the fact that URM physicians are more likely to care for underserved populations, those of lower socioeconomic status, non-English–speaking patients, those on Medicaid, and those who are uninsured, which may impact renumeration. Minority tax experienced by URM faculty includes mentoring URM medical students, providing cultural expertise to departments and institutions, and participating in community service projects and outreach programs. Specifically, many institutional committees require the participation of a URM member, resulting in URM faculty members experiencing higher committee service burden. Many, if not all, of these responsibilities often are not compensated through salary or academic promotion.

A Call to Action

There are several steps that can be taken to create a pathway to dermatology that is inclusive, flexible, and supportive of URMs.

• Increase early exposure to dermatology in medical school. Early exposure and mentorship opportunities are associated with higher rates of students pursuing specialty field careers.³⁴ Increased early opportunities allow for URM students to consider and explore a career in dermatology; receive mentorship; and ensure that dermatology, including topics related to skin of color (SOC), is incorporated into their learning. The American Academy of Dermatology has contributed to these efforts by its presence at every national meeting of the Student National Medical Association and Latino Medical Student Association, as well as its involvement with Nth Dimensions, which offers various educational opportunities for URM medical students.

• Implement equitable grading and holistic review processes in medical school. Racial/ethnic differences in clinical grading and standardized test scores in medical school demonstrate why holistic review of dermatology residency applicants is needed and why other metrics such as USMLE scores and AΩA status should be de-emphasized or eliminated when evaluating candidates. To support equity, many medical schools have eliminated honors grading, and some schools have eliminated AΩA distinction.

• Increase diversity of dermatology residents and residency programs. Implicit bias training for a medical school admissions committee has been shown to increase diversity in medical school enrollment.³⁵ Whether implicit bias training and other diversity training may benefit dermatology residency selection must be examined, including study of unintended consequences, such as reduced diversity, increased microaggressions toward minority colleagues, and the illusion of fairness.^36-39 Increasing representation is not sufficient—creating inclusive residency training environments is a critical parallel aim. Prioritizing diversity in dermatology residency recruitment is imperative. Creating dermatology residency positions specifically for URM residents may be an important option, as done at the University of Pennsylvania (Philadelphia, Pennsylvania) and Duke University (Durham, North Carolina).

• Create effective programs for URM mentorship. Due to the competitive nature of dermatology residency, the need for mentors in dermatology is critically vital for URM medical students, especially those without a home dermatology program at their medical school. Further development of formal mentorship and pipeline programs is essential at both the local and national levels. Some national examples of these initiatives include diversity mentorship programs offered by the American Academy of Dermatology, Skin of Color Society, Women’s Dermatologic Society, and Student National Medical Association. Many institutional programs also offer invaluable opportunities, such as the summer research fellowship at the University of California, San Francisco (UCSF); visiting clerkship grants for URMs at the University of Pennsylvania (Philadelphia, Pennsylvania) and Johns Hopkins University (Baltimore, Maryland); and integrated programs, such as the Visiting Elective Scholarship Program at UCSF, which provides funding and faculty mentorship for URM students completing an away rotation at UCSF.

• Establish longitudinal skin-of-color curricula and increased opportunities for research. More robust SOC training may lead to an increasingly diverse workforce. It is important that medical student and dermatology resident and fellow education include training on SOC to ensure high-quality care to diverse patient populations, which also may enhance the knowledge of trainees, encourage clinical and research interest in this field, and reduce health care disparities. Increasing research opportunities and offering formalized longitudinal training in SOC as well as incorporating more diverse images in medical school education may foster greater interest in this field at a time when trainees are establishing their career interests. At present, there is considerable room for improvement. Nijhawan et al⁴⁰ surveyed 63 dermatology chief residents and 41 program directors and found only 14.3% and 14.6%, respectively, reported having an expert who conducts clinic specializing in SOC. Only 52.4% and 65.9% reported having didactic sessions or lectures focused on SOC diseases, and 30.2% and 12.2% reported having a dedicated rotation for residents to gain experience in SOC.⁴⁰ A more recent study showed that when faculty were asked to incorporate more SOC content into lectures, the most commonly identified barrier to implementation was a lack of SOC images.⁴¹ Additionally, there remains a paucity of published research on this topic, with SOC articles representing only 2.7% of the literature.⁴² These numbers demonstrate the continued need for a more inclusive and comprehensive curriculum in dermatology residency programs and more robust funding for SOC research.

• Recruit and support URM faculty. Increasing diversity in dermatology residency programs likely will increase the number of potential URMs pursuing additional fellowship training and academic dermatology with active career mentorship and support. In addition, promoting faculty retention by combatting the progressive loss of URMs at all faculty levels is paramount. Mentorship for URM physicians has been shown to play a key role in the decision to pursue academic medicine as well as academic productivity and job satisfaction.^43,44 The visibility, cultural competency, clinical work, academic productivity, and mentorship efforts that URM faculty provide are essential to enhancing patient care, teaching diverse groups of learners, and recruiting more diverse trainees. Protected time to participate in professional development opportunities has been shown to improve recruitment and retention of URM faculty and offer additional opportunities for junior faculty to find mentors.^35,36 Incentivizing clinical care of underserved populations also may augment financial stability for URM physicians who choose to care for these patients. Finally, diversity work and community service should be legitimized and count toward faculty promotion.

Conclusion

There are numerous factors that contribute to the leaky pipeline in dermatology (eFigure). Many challenges that are unique to the URM population disadvantage these students from entering medical school, applying to dermatology residency, matching into dermatology fellowships, pursuing and staying in faculty positions, and achieving faculty advancement into leadership positions. With each progressive step along this trajectory, there is less minority representation. All dermatologists, regardless of race/ethnicity, need to play an active role and must prioritize diversity, equity, and inclusion efforts at all levels of education and training for the betterment of the specialty.

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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

The antidepressant bupropion failed to improve sexual dysfunction in female cancer survivors, according to new findings published online in the Journal of Clinical Oncology.

Using the Female Sexual Function Index (FSFI) as a measurement tool, investigators found that desire scores were not significantly different for participants who received bupropion versus a placebo over the 9-week study period.

“Sexual health is a complex phenomenon and [our results suggest that] no one intervention is going to solve the broader issue,” lead author Debra Barton, RN, PhD, FAAN, professor in the School of Nursing at the University of Michigan, Ann Arbor, told this news organization.

Sexual dysfunction is common among cancer survivors and experienced across multiple cancer types and stages of disease. Research shows that as many as 70% of female cancer survivors report loss of desire, compared with up to one-third of the general population.

Common sexual concerns among female cancer survivors include low desire, arousal issues, lack of appropriate lubrication, difficulty in achieving orgasm, and pain with penetrative sexual activity. Additionally, these women may experience significant overlap of symptoms, and often encounter multiple sexual issues that are exacerbated by a range of cancer treatments.

“It’s a huge problem,” Maryam B. Lustberg, MD, MPH, from Yale Cancer Center, New Haven, Conn., and colleagues wrote in an accompanying editorial.

Despite the prevalence of sexual dysfunction among cancer survivors, effective treatments remain elusive. Preliminary evidence suggests that bupropion, already approved for seasonal affective disorder, major depressive disorder, and smoking cessation, may also enhance libido.

Dr. Barton and colleagues conducted this phase 2 trial to determine whether bupropion can improve sexual desire in female cancer survivors without undesirable side effects.

In the study, Dr. Barton and colleagues compared two dose levels of extended-release bupropion in a cohort of 230 postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (<3.3), who had completed definitive cancer therapy.

Participants were randomized to receive either 150 mg (79 patients) or 300 mg (74 patients) once daily of extended-release bupropion, or placebo (77 patients).

Barton and colleagues then evaluated whether sexual desire significantly improved over the 9-week study period comparing the bupropion arms and the placebo group.

Overall, the authors found no significant differences (mean between-arm change for 150 mg once daily and placebo of 0.02; P = .93; mean between-arm change for 300 mg once daily and placebo of –0.02; P = .92). Mean scores at 9 weeks on the desire subscale were 2.17, 2.27, and 2.30 for 150 mg, 300 mg, and the placebo group, respectively.

In addition, none of the subscales – which included arousal, lubrication, and orgasm – or the total score showed a significant difference between arms at either 5 or 9 weeks.

Bupropion did, however, appear to be well tolerated. No grade 4-5 treatment-related adverse events occurred. In the 150-mg bupropion arm, two patients (2.6%) experienced a grade 3 event (insomnia and headache) and one patient in the 300-mg bupropion arm (1.4%) and placebo arm (1.3%) experienced a grade 3 event related to treatment (hypertension and headache, respectively).

In the accompanying editorial, Dr. Lustberg and colleagues “applaud the authors for conducting a study in this population of cancer survivors,” noting that “evidenced-based approaches have not been extensively studied.”

Dr. Lustberg and colleagues also commented that other randomized controlled clinical trials evaluating sexual desire disorder assessed outcomes using additional metrics, such as the Female Sexual Distress Scale–Revised questionnaire, which measures distress related to sexual dysfunction and low desire, in particular.

“The use of specific validated instruments for libido in place of the FSFI might have helped determine the effect of the study intervention in this reported trial,” they wrote.

Overall, according to Dr. Lustberg and colleagues, the negative results of this study indicate that a multidisciplinary clinical approach may be needed.

“As much as we would like to have one intervention that addresses this prominent issue, the evidence strongly suggests that cancer-related sexual problems may need an integrative biopsychosocial model that intervenes on biologic, psychologic, interpersonal, and social-cultural factors, not just on one factor, such as libido,” they wrote. “Such work may require access to multidisciplinary care with specialists in women’s health, pelvic floor rehabilitation, and psychosocial oncology.”

Dr. Barton said she has been developing a multicomponent approach to addressing sexual health in female cancer survivors.

However, she noted, “there is still much we do not fully understand about the broader impact of the degree of hormone deprivation in the population of female cancer survivors. A better understanding would provide clearer targets for interventions.” 

The study was supported by the National Cancer Institute and Breast Cancer Research Foundation. Dr. Barton has disclosed research funding from Merck. Dr. Lustberg reported receiving honoraria from Novartis and Biotheranostics; consulting or advising with PledPharma, Disarm Therapeutics, Pfizer; and other relationships with Cynosure/Hologic.

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