Women's Health

The psychedelic psilocybin may have a role in the treatment of anorexia nervosa (AN), an eating disorder that is notoriously difficult and costly to treat.

In a very small phase 1 trial of 10 women with AN, a single 25-mg dose of psilocybin, coupled with psychological support, was safe and well-tolerated and decreased eating-disorder behaviors in some of the participants.

University of California San Diego

Stephanie Knatz Peck, PhD, and colleagues with the eating disorders treatment & research center, University of California San Diego, write that the “robust response” in a subset of women after a single dose of psilocybin is “notable,” given that currently available treatments for adult anorexia result in only modest improvements in symptoms and often focus on weight and nutritional rehabilitation without adequately addressing underlying psychopathology.

However, given this was a small, phase 1, open-label feasibility study, these effects are “preliminary and inconclusive,” they caution.

The study was published online in Nature Medicine.
 

Meaningful experience

The 10 women in the study met DSM-5 criteria for AN or partial remission of AN. They were between age 18 and 40 years with a mean body mass index (BMI) of 19.7 kg/m².

Following the single 25-mg dose of psilocybin, no clinically significant changes were observed in ECG, vital signs, laboratory values, or suicidality.

All adverse events were mild and mirrored typical psilocybin-associated symptoms such as transient headache, nausea, and fatigue.

Psilocybin was associated with reduced levels of anxiety and preoccupations surrounding food, eating, and body shape at the 1-month follow-up.

Weight concerns decreased significantly at the 1-month (P = .036, Cohen’s d = .78) and 3-month (P = .04, d = .78) follow-up, with a medium to large effect.

Shape concerns significantly decreased at 1-month follow-up (P = .036, d = .78) but were no longer significant at 3-month follow-up (P = .081, d = .62).

Four of the 10 women (40%) had clinically significant reductions in eating disorder scores at 3 months, which qualified for remission from eating-disorder psychopathology.

However, the researchers caution that the effects on eating disorder psychopathology were “highly variable.”

On average, changes in BMI were not significant during the 3 months following psilocybin treatment. However, five women had an increase in BMI at 3 months, ranging from 0.4 to 1.2 kg/m².

Overall, the psilocybin experience was regarded as meaningful by participants; 80% endorsed the experience as one of the top five most meaningful of life; 90% endorsed feeling more positive about life endeavors; and 70% reported experiencing a shift in personal identity and overall quality of life.

The vast majority of women (90%) felt that one dosing session was not enough.

The fact that the treatment was regarded as beneficial by most women and that there were no dropouts are “promising signs of engagement,” given that dropout rates for currently available AN treatments tend to be high, the researchers note.

They urge caution in interpreting the results considering they were based on a small sample size and did not include a placebo group. They note that larger, adequately powered, randomized controlled trials are needed to draw any conclusions about the role of psilocybin for anorexia nervosa.
 

Encouraging data

The coauthors of a Nature Medicine News & Views commentary say this “encouraging” phase 1 trial “underscores the necessity for more research into classic psychedelics to address the urgent need for effective treatments” for AN.

Outside experts also weighed in on the study in a statement from the U.K.-based nonprofit Science Media Centre.

Alexandra Pike, DPhil, MSc, with University of York, England, noted that this study is “a first step in showing that psilocybin may be a safe treatment for those with anorexia nervosa, but we cannot conclude from this work that it will be effective in this chronic, complex illness.”

Trevor Steward, MD, with University of Melbourne, noted that psilocybin therapy has provided “glimmers of hope in other mental health disorders, notably by providing evidence that it can improve anxiety, cognitive flexibility, and self-acceptance for some people. These are all features of anorexia nervosa and the rationale for exploring psilocybin therapy as an option in the case of anorexia is strong.”

Dr. Steward also noted that the field is only beginning to “scratch the surface in terms of understanding how psilocybin impacts the brain. Dedicated funding to exploring how it specifically acts to target anorexia nervosa symptoms is crucial to advancing this important avenue of research.

“As there are no approved medications available specifically for anorexia nervosa treatment, psilocybin therapy may prove to be a promising option, though additional research is needed to test this,” Dr. Steward said.

The study used an investigational synthetic formulation of psilocybin (COMP360 psilocybin) developed by COMPASS Pathways, which funded the study. Two coauthors have financial and scientific relationships with COMPASS Pathways. The commentary authors and Dr. Steward report no relevant financial relationships.

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

The psychedelic psilocybin may have a role in the treatment of anorexia nervosa (AN), an eating disorder that is notoriously difficult and costly to treat.

In a very small phase 1 trial of 10 women with AN, a single 25-mg dose of psilocybin, coupled with psychological support, was safe and well-tolerated and decreased eating-disorder behaviors in some of the participants.

University of California San Diego

Stephanie Knatz Peck, PhD, and colleagues with the eating disorders treatment & research center, University of California San Diego, write that the “robust response” in a subset of women after a single dose of psilocybin is “notable,” given that currently available treatments for adult anorexia result in only modest improvements in symptoms and often focus on weight and nutritional rehabilitation without adequately addressing underlying psychopathology.

However, given this was a small, phase 1, open-label feasibility study, these effects are “preliminary and inconclusive,” they caution.

The study was published online in Nature Medicine.
 

Meaningful experience

The 10 women in the study met DSM-5 criteria for AN or partial remission of AN. They were between age 18 and 40 years with a mean body mass index (BMI) of 19.7 kg/m².

Following the single 25-mg dose of psilocybin, no clinically significant changes were observed in ECG, vital signs, laboratory values, or suicidality.

All adverse events were mild and mirrored typical psilocybin-associated symptoms such as transient headache, nausea, and fatigue.

Psilocybin was associated with reduced levels of anxiety and preoccupations surrounding food, eating, and body shape at the 1-month follow-up.

Weight concerns decreased significantly at the 1-month (P = .036, Cohen’s d = .78) and 3-month (P = .04, d = .78) follow-up, with a medium to large effect.

Shape concerns significantly decreased at 1-month follow-up (P = .036, d = .78) but were no longer significant at 3-month follow-up (P = .081, d = .62).

Four of the 10 women (40%) had clinically significant reductions in eating disorder scores at 3 months, which qualified for remission from eating-disorder psychopathology.

However, the researchers caution that the effects on eating disorder psychopathology were “highly variable.”

On average, changes in BMI were not significant during the 3 months following psilocybin treatment. However, five women had an increase in BMI at 3 months, ranging from 0.4 to 1.2 kg/m².

Overall, the psilocybin experience was regarded as meaningful by participants; 80% endorsed the experience as one of the top five most meaningful of life; 90% endorsed feeling more positive about life endeavors; and 70% reported experiencing a shift in personal identity and overall quality of life.

The vast majority of women (90%) felt that one dosing session was not enough.

The fact that the treatment was regarded as beneficial by most women and that there were no dropouts are “promising signs of engagement,” given that dropout rates for currently available AN treatments tend to be high, the researchers note.

They urge caution in interpreting the results considering they were based on a small sample size and did not include a placebo group. They note that larger, adequately powered, randomized controlled trials are needed to draw any conclusions about the role of psilocybin for anorexia nervosa.
 

Encouraging data

The coauthors of a Nature Medicine News & Views commentary say this “encouraging” phase 1 trial “underscores the necessity for more research into classic psychedelics to address the urgent need for effective treatments” for AN.

Outside experts also weighed in on the study in a statement from the U.K.-based nonprofit Science Media Centre.

Alexandra Pike, DPhil, MSc, with University of York, England, noted that this study is “a first step in showing that psilocybin may be a safe treatment for those with anorexia nervosa, but we cannot conclude from this work that it will be effective in this chronic, complex illness.”

Trevor Steward, MD, with University of Melbourne, noted that psilocybin therapy has provided “glimmers of hope in other mental health disorders, notably by providing evidence that it can improve anxiety, cognitive flexibility, and self-acceptance for some people. These are all features of anorexia nervosa and the rationale for exploring psilocybin therapy as an option in the case of anorexia is strong.”

Dr. Steward also noted that the field is only beginning to “scratch the surface in terms of understanding how psilocybin impacts the brain. Dedicated funding to exploring how it specifically acts to target anorexia nervosa symptoms is crucial to advancing this important avenue of research.

“As there are no approved medications available specifically for anorexia nervosa treatment, psilocybin therapy may prove to be a promising option, though additional research is needed to test this,” Dr. Steward said.

The study used an investigational synthetic formulation of psilocybin (COMP360 psilocybin) developed by COMPASS Pathways, which funded the study. Two coauthors have financial and scientific relationships with COMPASS Pathways. The commentary authors and Dr. Steward report no relevant financial relationships.

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

The psychedelic psilocybin may have a role in the treatment of anorexia nervosa (AN), an eating disorder that is notoriously difficult and costly to treat.

In a very small phase 1 trial of 10 women with AN, a single 25-mg dose of psilocybin, coupled with psychological support, was safe and well-tolerated and decreased eating-disorder behaviors in some of the participants.

University of California San Diego

Stephanie Knatz Peck, PhD, and colleagues with the eating disorders treatment & research center, University of California San Diego, write that the “robust response” in a subset of women after a single dose of psilocybin is “notable,” given that currently available treatments for adult anorexia result in only modest improvements in symptoms and often focus on weight and nutritional rehabilitation without adequately addressing underlying psychopathology.

However, given this was a small, phase 1, open-label feasibility study, these effects are “preliminary and inconclusive,” they caution.

The study was published online in Nature Medicine.
 

Meaningful experience

The 10 women in the study met DSM-5 criteria for AN or partial remission of AN. They were between age 18 and 40 years with a mean body mass index (BMI) of 19.7 kg/m².

Following the single 25-mg dose of psilocybin, no clinically significant changes were observed in ECG, vital signs, laboratory values, or suicidality.

All adverse events were mild and mirrored typical psilocybin-associated symptoms such as transient headache, nausea, and fatigue.

Psilocybin was associated with reduced levels of anxiety and preoccupations surrounding food, eating, and body shape at the 1-month follow-up.

Weight concerns decreased significantly at the 1-month (P = .036, Cohen’s d = .78) and 3-month (P = .04, d = .78) follow-up, with a medium to large effect.

Shape concerns significantly decreased at 1-month follow-up (P = .036, d = .78) but were no longer significant at 3-month follow-up (P = .081, d = .62).

Four of the 10 women (40%) had clinically significant reductions in eating disorder scores at 3 months, which qualified for remission from eating-disorder psychopathology.

However, the researchers caution that the effects on eating disorder psychopathology were “highly variable.”

On average, changes in BMI were not significant during the 3 months following psilocybin treatment. However, five women had an increase in BMI at 3 months, ranging from 0.4 to 1.2 kg/m².

Overall, the psilocybin experience was regarded as meaningful by participants; 80% endorsed the experience as one of the top five most meaningful of life; 90% endorsed feeling more positive about life endeavors; and 70% reported experiencing a shift in personal identity and overall quality of life.

The vast majority of women (90%) felt that one dosing session was not enough.

The fact that the treatment was regarded as beneficial by most women and that there were no dropouts are “promising signs of engagement,” given that dropout rates for currently available AN treatments tend to be high, the researchers note.

They urge caution in interpreting the results considering they were based on a small sample size and did not include a placebo group. They note that larger, adequately powered, randomized controlled trials are needed to draw any conclusions about the role of psilocybin for anorexia nervosa.
 

Encouraging data

The coauthors of a Nature Medicine News & Views commentary say this “encouraging” phase 1 trial “underscores the necessity for more research into classic psychedelics to address the urgent need for effective treatments” for AN.

Outside experts also weighed in on the study in a statement from the U.K.-based nonprofit Science Media Centre.

Alexandra Pike, DPhil, MSc, with University of York, England, noted that this study is “a first step in showing that psilocybin may be a safe treatment for those with anorexia nervosa, but we cannot conclude from this work that it will be effective in this chronic, complex illness.”

Trevor Steward, MD, with University of Melbourne, noted that psilocybin therapy has provided “glimmers of hope in other mental health disorders, notably by providing evidence that it can improve anxiety, cognitive flexibility, and self-acceptance for some people. These are all features of anorexia nervosa and the rationale for exploring psilocybin therapy as an option in the case of anorexia is strong.”

Dr. Steward also noted that the field is only beginning to “scratch the surface in terms of understanding how psilocybin impacts the brain. Dedicated funding to exploring how it specifically acts to target anorexia nervosa symptoms is crucial to advancing this important avenue of research.

“As there are no approved medications available specifically for anorexia nervosa treatment, psilocybin therapy may prove to be a promising option, though additional research is needed to test this,” Dr. Steward said.

The study used an investigational synthetic formulation of psilocybin (COMP360 psilocybin) developed by COMPASS Pathways, which funded the study. Two coauthors have financial and scientific relationships with COMPASS Pathways. The commentary authors and Dr. Steward report no relevant financial relationships.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

The Food and Drug Administration is considering approving a postpartum depression medication that can start working rapidly – in as little as 3 days. Promising results for the drug, zuranolone, were published recently in The American Journal of Psychiatry.

Approximately 17% of women are affected by postpartum depression (PPD) during pregnancy or after birth, study authors noted. The condition often results in reduced breastfeeding, poor maternal-infant bonding, and hindering behavioral, emotional and brain development of the baby. Severe PPD can lead to suicide of the mother, which accounts for 20% of all postpartum deaths, they wrote.

The study included 196 people who had given birth in the past year, and were between the ages of 18 and 45 years old. Participants had major depression that began in the 3rd trimester of pregnancy or during the first 4 weeks of the postpartum period. Among participants, 22% were Black and 38% were Hispanic.

Of those who took zuranolone, 57% had significantly improved depression symptoms after taking the drug for 14 days, and 27% were in remission at the conclusion of the 14-day treatment. The average time it took for symptoms to significantly decline was 9 days. Most people who saw improvements had them continue for the entire 45-day follow-up period. The most common side effects were drowsiness, dizziness, and sleepiness.

Currently, PPD treatment includes taking antidepressants, which can take up to 12 weeks to work. 

Researchers noted that the limitations of the study were that it only included women with severe PPD, and that women with a history of bipolar or psychotic disorders were excluded. Women in the study were not allowed to breastfeed, so the effect of zuranolone on lactation is unknown, they wrote.

A February news release from drugmaker Biogen indicated the FDA may decide whether to approve the medicine by Aug. 5.

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

Women in the United States are dying of alcohol-related causes at a much faster rate than are U.S. men, according to a new study that tracked these deaths for 20 years. The most dramatic rise occurred in the last 3 years covered by the study, published in JAMA Network Open.

“From 2018 to 2020, there was an increase of 14.7% per year” in alcohol-related deaths in women, said study researcher Ibraheem M. Karaye, MD, DrPH, assistant professor of population health, and director of the health science program at Hofstra University in Hempstead, N.Y. While alcohol-related deaths in men also rose greatly during that same 3-year period, the increase was less than in women, at 12.5% per year.

Researchers have known for several years that the sex gap related to alcohol use and complications is narrowing. Women are drinking more, engaging in more high-risk drinking, and increasingly developing alcohol use disorder, Dr. Karaye said. “However, we know very little about the trends in alcohol-related deaths.”

Using a Centers for Disease Control and Prevention database that spanned the years 1999 to 2020, Dr. Karaye and his coresearchers analyzed files that identified underlying causes of death. During those years, more than 605,000 alcohol-attributed deaths were identified. Overall, men were still nearly three times more likely to die from alcohol-related issues than were women. However, the rate of alcohol-related deaths in women increased steadily and, in the latest years studied, more greatly than in men. 

“We found there were three different segments of trends in women,” Dr. Karaye said. The rates increased slowly, then steadily picked up speed. For instance:

• 1999-2007: “We found that mortality rates from alcohol were increasing by 1% per year” in women, he said.
• 2007-2018: “The rate increased 4.3% per year. That was a big one, but not as phenomenal as the most recent, the most concerning,” he said. 
• 2018 to 2020: The rate increased 14.7% per year in women, compared with 12.5% per year for men.

The findings stayed strong, Dr. Karaye said, even when the researchers excluded data from the year 2020, the first pandemic year. 
 

Explaining the increase

“Our study is descriptive; it tells us the ‘what’ but not the ‘why,’” Dr. Karaye said. “However, we can speculate based on what’s known and previous research.” Women are drinking at higher rates than before and tend to develop more alcohol-related complications than men do.

Women have lower concentrations of the enzyme called alcohol dehydrogenase, which helps breaks down and metabolize alcohol. “We know that in women the concentration of fat to water is higher, so that also leads to a possibly higher concentration of alcohol,” Dr. Karaye said.

The study findings point to the need for more research to focus on causes for the rise in women, Dr. Karaye said. Studies on the use of medication for alcohol use disorder need to represent women more equitably, he said.
 

Other findings on women, alcohol

Other recent research has found that the proportion of suicides that involved alcohol has also increased for women of all age groups, but not men. In research published in 2022, researchers analyzed more than 115,000 deaths by suicide from 2003 to 2018 and found the proportion of those deaths involving alcohol at a level above the legal limit increased annually for women in all age groups, but not for men. 

A review by Mayo Clinic researchers found that women are increasingly affected by liver disease linked to alcohol and develop more severe disease at lower levels of drinking than do men. Among other factors, the researchers said that an increase in obesity, which can worsen the liver-damaging effects of alcohol, is a contributor.  
 

Expert perspectives

Overall, recent research is showing that, “not only are women drinking more but potentially are developing more problems later on as a result of the alcohol,” said Mark S. Kaplan, DrPH, professor emeritus of social welfare at the University of California, Los Angeles. He conducted the study finding growing alcohol use involvement in women’s death by suicide.

“I think this new study is strong,” he said. In future research, “we should focus on some of the issues that may have to do with social circumstances.” 

In particular, he said, research should examine the increase in alcohol-involved death found in the new study among American Indian or Alaska Native women. While the overall annual increase was 14.7% for the years 2018-2020, the rate among American Indian or Alaska Native women was 22.8% annually. 

While the new study and others find the gap between the sexes is narrowing for alcohol-related complications, “unfortunately, alcohol use disorder and alcohol-related deaths are increasing in both men and women,” said Camille A. Kezer, MD, a gastroenterology and hepatology fellow at Mayo Clinic, who led the review on sex differences in alcohol-linked liver disease.  

However, she said, “we know that there are risks of alcohol that are unique to women for a variety of reasons, including differences in metabolism and the impact of hormones, as well as the increasing prevalence of obesity and bariatric surgery in women.” 

Bariatric surgery has been linked with an increase in alcohol consumption and disorder in some studies. 

Dr. Kezer’s advice to women: “Limit alcohol intake to one drink per day or less. If you are concerned about your alcohol intake, you should seek help.”  

Health care providers are committed to helping their patients recognize and treat alcohol-related disorders, she said.

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

Women in the United States are dying of alcohol-related causes at a much faster rate than are U.S. men, according to a new study that tracked these deaths for 20 years. The most dramatic rise occurred in the last 3 years covered by the study, published in JAMA Network Open.

“From 2018 to 2020, there was an increase of 14.7% per year” in alcohol-related deaths in women, said study researcher Ibraheem M. Karaye, MD, DrPH, assistant professor of population health, and director of the health science program at Hofstra University in Hempstead, N.Y. While alcohol-related deaths in men also rose greatly during that same 3-year period, the increase was less than in women, at 12.5% per year.

Researchers have known for several years that the sex gap related to alcohol use and complications is narrowing. Women are drinking more, engaging in more high-risk drinking, and increasingly developing alcohol use disorder, Dr. Karaye said. “However, we know very little about the trends in alcohol-related deaths.”

Using a Centers for Disease Control and Prevention database that spanned the years 1999 to 2020, Dr. Karaye and his coresearchers analyzed files that identified underlying causes of death. During those years, more than 605,000 alcohol-attributed deaths were identified. Overall, men were still nearly three times more likely to die from alcohol-related issues than were women. However, the rate of alcohol-related deaths in women increased steadily and, in the latest years studied, more greatly than in men. 

“We found there were three different segments of trends in women,” Dr. Karaye said. The rates increased slowly, then steadily picked up speed. For instance:

• 1999-2007: “We found that mortality rates from alcohol were increasing by 1% per year” in women, he said.
• 2007-2018: “The rate increased 4.3% per year. That was a big one, but not as phenomenal as the most recent, the most concerning,” he said. 
• 2018 to 2020: The rate increased 14.7% per year in women, compared with 12.5% per year for men.

The findings stayed strong, Dr. Karaye said, even when the researchers excluded data from the year 2020, the first pandemic year. 
 

Explaining the increase

“Our study is descriptive; it tells us the ‘what’ but not the ‘why,’” Dr. Karaye said. “However, we can speculate based on what’s known and previous research.” Women are drinking at higher rates than before and tend to develop more alcohol-related complications than men do.

Women have lower concentrations of the enzyme called alcohol dehydrogenase, which helps breaks down and metabolize alcohol. “We know that in women the concentration of fat to water is higher, so that also leads to a possibly higher concentration of alcohol,” Dr. Karaye said.

The study findings point to the need for more research to focus on causes for the rise in women, Dr. Karaye said. Studies on the use of medication for alcohol use disorder need to represent women more equitably, he said.
 

Other findings on women, alcohol

Other recent research has found that the proportion of suicides that involved alcohol has also increased for women of all age groups, but not men. In research published in 2022, researchers analyzed more than 115,000 deaths by suicide from 2003 to 2018 and found the proportion of those deaths involving alcohol at a level above the legal limit increased annually for women in all age groups, but not for men. 

A review by Mayo Clinic researchers found that women are increasingly affected by liver disease linked to alcohol and develop more severe disease at lower levels of drinking than do men. Among other factors, the researchers said that an increase in obesity, which can worsen the liver-damaging effects of alcohol, is a contributor.  
 

Expert perspectives

Overall, recent research is showing that, “not only are women drinking more but potentially are developing more problems later on as a result of the alcohol,” said Mark S. Kaplan, DrPH, professor emeritus of social welfare at the University of California, Los Angeles. He conducted the study finding growing alcohol use involvement in women’s death by suicide.

“I think this new study is strong,” he said. In future research, “we should focus on some of the issues that may have to do with social circumstances.” 

In particular, he said, research should examine the increase in alcohol-involved death found in the new study among American Indian or Alaska Native women. While the overall annual increase was 14.7% for the years 2018-2020, the rate among American Indian or Alaska Native women was 22.8% annually. 

While the new study and others find the gap between the sexes is narrowing for alcohol-related complications, “unfortunately, alcohol use disorder and alcohol-related deaths are increasing in both men and women,” said Camille A. Kezer, MD, a gastroenterology and hepatology fellow at Mayo Clinic, who led the review on sex differences in alcohol-linked liver disease.  

However, she said, “we know that there are risks of alcohol that are unique to women for a variety of reasons, including differences in metabolism and the impact of hormones, as well as the increasing prevalence of obesity and bariatric surgery in women.” 

Bariatric surgery has been linked with an increase in alcohol consumption and disorder in some studies. 

Dr. Kezer’s advice to women: “Limit alcohol intake to one drink per day or less. If you are concerned about your alcohol intake, you should seek help.”  

Health care providers are committed to helping their patients recognize and treat alcohol-related disorders, she said.

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

Women in the United States are dying of alcohol-related causes at a much faster rate than are U.S. men, according to a new study that tracked these deaths for 20 years. The most dramatic rise occurred in the last 3 years covered by the study, published in JAMA Network Open.

“From 2018 to 2020, there was an increase of 14.7% per year” in alcohol-related deaths in women, said study researcher Ibraheem M. Karaye, MD, DrPH, assistant professor of population health, and director of the health science program at Hofstra University in Hempstead, N.Y. While alcohol-related deaths in men also rose greatly during that same 3-year period, the increase was less than in women, at 12.5% per year.

Researchers have known for several years that the sex gap related to alcohol use and complications is narrowing. Women are drinking more, engaging in more high-risk drinking, and increasingly developing alcohol use disorder, Dr. Karaye said. “However, we know very little about the trends in alcohol-related deaths.”

Using a Centers for Disease Control and Prevention database that spanned the years 1999 to 2020, Dr. Karaye and his coresearchers analyzed files that identified underlying causes of death. During those years, more than 605,000 alcohol-attributed deaths were identified. Overall, men were still nearly three times more likely to die from alcohol-related issues than were women. However, the rate of alcohol-related deaths in women increased steadily and, in the latest years studied, more greatly than in men. 

“We found there were three different segments of trends in women,” Dr. Karaye said. The rates increased slowly, then steadily picked up speed. For instance:

• 1999-2007: “We found that mortality rates from alcohol were increasing by 1% per year” in women, he said.
• 2007-2018: “The rate increased 4.3% per year. That was a big one, but not as phenomenal as the most recent, the most concerning,” he said. 
• 2018 to 2020: The rate increased 14.7% per year in women, compared with 12.5% per year for men.

The findings stayed strong, Dr. Karaye said, even when the researchers excluded data from the year 2020, the first pandemic year. 
 

Explaining the increase

“Our study is descriptive; it tells us the ‘what’ but not the ‘why,’” Dr. Karaye said. “However, we can speculate based on what’s known and previous research.” Women are drinking at higher rates than before and tend to develop more alcohol-related complications than men do.

Women have lower concentrations of the enzyme called alcohol dehydrogenase, which helps breaks down and metabolize alcohol. “We know that in women the concentration of fat to water is higher, so that also leads to a possibly higher concentration of alcohol,” Dr. Karaye said.

The study findings point to the need for more research to focus on causes for the rise in women, Dr. Karaye said. Studies on the use of medication for alcohol use disorder need to represent women more equitably, he said.
 

Other findings on women, alcohol

Other recent research has found that the proportion of suicides that involved alcohol has also increased for women of all age groups, but not men. In research published in 2022, researchers analyzed more than 115,000 deaths by suicide from 2003 to 2018 and found the proportion of those deaths involving alcohol at a level above the legal limit increased annually for women in all age groups, but not for men. 

A review by Mayo Clinic researchers found that women are increasingly affected by liver disease linked to alcohol and develop more severe disease at lower levels of drinking than do men. Among other factors, the researchers said that an increase in obesity, which can worsen the liver-damaging effects of alcohol, is a contributor.  
 

Expert perspectives

Overall, recent research is showing that, “not only are women drinking more but potentially are developing more problems later on as a result of the alcohol,” said Mark S. Kaplan, DrPH, professor emeritus of social welfare at the University of California, Los Angeles. He conducted the study finding growing alcohol use involvement in women’s death by suicide.

“I think this new study is strong,” he said. In future research, “we should focus on some of the issues that may have to do with social circumstances.” 

In particular, he said, research should examine the increase in alcohol-involved death found in the new study among American Indian or Alaska Native women. While the overall annual increase was 14.7% for the years 2018-2020, the rate among American Indian or Alaska Native women was 22.8% annually. 

While the new study and others find the gap between the sexes is narrowing for alcohol-related complications, “unfortunately, alcohol use disorder and alcohol-related deaths are increasing in both men and women,” said Camille A. Kezer, MD, a gastroenterology and hepatology fellow at Mayo Clinic, who led the review on sex differences in alcohol-linked liver disease.  

However, she said, “we know that there are risks of alcohol that are unique to women for a variety of reasons, including differences in metabolism and the impact of hormones, as well as the increasing prevalence of obesity and bariatric surgery in women.” 

Bariatric surgery has been linked with an increase in alcohol consumption and disorder in some studies. 

Dr. Kezer’s advice to women: “Limit alcohol intake to one drink per day or less. If you are concerned about your alcohol intake, you should seek help.”  

Health care providers are committed to helping their patients recognize and treat alcohol-related disorders, she said.

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

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

Fifth pregnancy, first baby.

After four pregnancies resulted in losses – and doing things as natural as possible and leaving it up to the birds, bees, and fate – my husband and I decided to explore in vitro fertilization (IVF).

Drugs to direct my follicles to produce more eggs, an egg retrieval procedure, genetic testing of our embryos, a quick procedure to remove a residual uterine septum from my uterus, drugs to thicken my endometrial lining to prepare my body to receive an embryo, an embryo transfer, steroids to suppress my immune system so my body would accept the pregnancy, blood thinner shots to promote blood flow to the baby, and 10 weeks of progesterone in oil shots later and we’re days away from welcoming our first baby into our lives.

In short, there’s more than one way to define “miracle baby.”

Global estimates say 48 million couples and 186 million individuals struggle with infertility. On average, 2 million infants born in the United States each year are conceived through assisted reproductive technology and the demand for treatments like IVF have doubled in the last decade.

Now the need for treatments outweighs clinician availability. “We have about 1,250 practicing fertility physicians in the U.S. to serve the whole country, which is highly inadequate,” said Eduardo Hariton, MD, a reproductive endocrinology physician in San Francisco and managing director of the U.S. Fertility Innovation Fund. “We have people that want to get care waiting 1 to 3 months to be seen.”

Dr. Hariton explains that U.S. IVF clinics are performing around 250,000 to 300,000 IVF cycles per year and need to be doing a million-plus to meet demand. This, plus the cost of fertility treatments – an average IVF cycle runs $23,500 and the majority of patients need multiple cycles to conceive – keeps the barrier to entry high.

Enter technology: New advances are on the way to help the assisted fertility process to run smoother and be less costly. “The field is really coming into an age of great progress and innovation,” added S. Zev Williams, MD, PhD, chief of the division of reproductive endocrinology and Infertility at Columbia University Irving Medical Center, New York City.

I’m personally grateful that such technology exists. Here is a look at some recent game changers in reproductive tech and what the future may hold.
 

AI will help, of course

Fertility treatments involve endless analysis, diagnosis, and recommendations – dozens if not hundreds of decisions from each physician for each patient. Human action and reaction can affect this process, Dr. Hariton explained.

For example, if he hyperstimulated a woman during the follicle growing stage of her egg retrieval and ended up with eggs too large to retrieve, Dr. Hariton said he may subconsciously be more inclined to be extra cautious with his patients the week after, and vice versa.

This is where AI can help. “Rather than me making decisions from a couple of thousands of cycles of experience, I get to leverage hundreds of thousands of cycles from different providers over different people,” said Dr. Hariton. “I get to use all the data from that patient today – her age, her weight, what happened last cycle, how she’s doing – and make a very objective decision about the optimal time to give that woman or that couple the best outcome possible.”

AI can also assist with tasks like embryo grading. “Once our embryos are made in the lab, we usually have an embryologist looking at those embryos, grading them on a three-variable scale, and then picking the nicest one for transfer,” said Dr. Hariton. Machine learning computer vision software can help doctors select the best embryo.

Many of these AI products are in trials in the United States and some AI-based technology is already being used in fertility labs, especially in other countries. “ALife recently launched a suite of products to help with their decisions during stimulation that can help with the quality KPIs [key performance indicators] in the lab,” said Dr. Hariton. “There’s also a company that does AI-based predictions of success to give patients a better estimate called Univfy.” More AI products are still in development or awaiting Food and Drug Administration clearance.
 

Robots lend a hand

Like artificial intelligence, robots can be a big help in the IVF lab. Columbia University Fertility Center recently became the first to use an articulated (ART) robot to handle precise and highly repetitive work.

“IVF, from the initial point, involves creating these special plates where embryos can grow, and you do that by making little droplets,” said Dr. Williams. “It’s very time-consuming to create tons of these little droplets for the embryos to grow.” Thus, the lab created a robot to help squirt drops of the media substance required to sustain embryos in a way that is 10 times more precise than that of a trained embryologist.

“It’s a win-win because you allow the robots to do things better than a human can and this allows the humans to do things that a robot just can’t do,” explained Dr. Williams. He and his team began using this technology in the beginning of November 2022.

Dr. Williams sees ART robots being used in many more parts of the fertility treatment journey along the way, like preparing eggs after they are retrieved and performing intracytoplasmic sperm injection (ICSI), with the robot injecting the sperm into the egg.

Launching with the plate making, said Dr. Williams, is a low stakes entry point for robotic technology in the lab. “It allows us to introduce robotics to automate and optimize each step along the way, but to do so in the safest possible way.”

Dr. Williams estimates that robots will have their hands on actual eggs and sperm in 5 years.
 

Updates in genetic testing

Currently, if a couple wants to have their embryos genetically tested, also known as preimplantation genetic testing, each embryo must be frozen, then a biopsy of that embryo is performed and sent to the lab.

“It takes time to get the results,” said Dr. Williams. “The whole time you’re waiting, you don’t know if you’re going to have any embryos that are transferable or if next month you’re going to have to do another IVF cycle.”

Columbia researchers recently developed a new in-house test that can determine if a fetus or embryo has the right number of chromosomes. This STORK (Short-read Transpore Rapid Karyotyping) can be performed without freezing embryos and sending them out, which Dr. Williams said can save couples money and time, as they won’t necessarily need to do a separate embryo transfer cycle and can transfer an embryo in the same cycle. “You can test in the morning and transfer in the afternoon,” said Dr. Williams.

The test is currently awaiting approval and will first be used to test miscarriage samples to see if embryos were genetically normal or not, which he said should cost around $200 vs. the $2,000 to $4,000 it can cost to have fetal tissue sent to the lab – and insurance doesn’t cover the procedure until after a second or third miscarriage.

This, said Dr. Williams, should be in the field in less than a year, and he estimates that the test will be used for fresh embryos in about a year and a half.
 

Sperm collection made simpler

Typically, a man delivers a sperm sample in a room at an IVF clinic or by collecting a sample at home and rushing it to the clinic before it degrades, which Dr. Williams said can happen in as little as 15 minutes.

In 2020, Dr. Williams and his team began using a custom at-home sperm collection box that houses sperm in a recyclable foam container that holds a sample cup, which is filled with special sperm-supporting media, at an angle that prevents evaporation and maintains temperature and pH. This allows patients to collect samples in the comfort of their homes and increases the clock to 3 hours.

“It’s great for the patients because it’s much more comfortable,” said Dr. Williams, who notes that having to “perform” on site can be stressful for men. Studies the team has conducted have shown sperm collected in this manner have a better success rate than those collected in the lab, and 90% of Columbia’s Fertility Center patients are now providing sperm samples this way.

Similar innovations to deliver sperm, like Protex, are now on the market, while companies like myLabBox and Legacy are offering at-home sperm testing kits to mail in for a full semen analysis.
 

At-home monitoring: More and better

Wearable reproductive health devices are also helping more women get pregnant. “I am very excited about biometric data harnessed in wearables to predict periods, ovulation, and fertility,” said Amander Clark, PhD, director of the UCLA Center for Reproductive Science, Health, and Education, Los Angeles.

The Tempdrop Fertility and Ovulation Tracker, for instance, is a wearable sensor with an accompanying charting app that helps a woman identify her most fertile days to conceive. The Bellabeat Ivy is a women’s health smart bracelet with a strong focus on tracking a woman’s cycle and fertility, pregnancy, and postnatal symptoms. And Mirvie, which is currently in development, is a blood test that will be able to predict pregnancy complications earlier.

Physicians are also looking to move as much of the lab experience as they can into a patient’s home, which streamlines processes while offering privacy and comfort. For example, Dr. Hariton, who runs a strategic venture capital fund for physicians, said his team is currently working with a company that does remote ultrasounds.

And Mira, an at-home hormone monitor, uses patented AI algorithms to accurately measure the levels of major reproductive health hormones (E3G, LH, PdG, FSH) in urine, said Meir Olcha, MD, chief medical officer at Sama Fertility. The product recently completed a clinical trial, which showed it was a viable alternative to blood serum for patients undergoing IVF.
 

Stem cells could make eggs ageless

Research shows that a woman’s egg quality decreases gradually but significantly starting at age 32 and more rapidly after 37. Sperm quality may also decrease with age. A possible workaround: Scientists are actively researching how to create eggs and sperm from stem cells.

“I think getting eggs from stem cells will happen in the future,” said Dr. Hariton, who notes that this type of technology would be a game changer in his clinic. “It will make some of the hardest diagnoses that I have – which is on a daily basis, ‘I’m so sorry, you’re in premature menopause’ or ‘I don’t think we’re going to be successful getting you pregnant with your own eggs; here are some other options like donor eggs’ – much better,” he added. And stem cells are currently being used to research causes of infertility.

Clinics like UCLA have already been making strides. “We are using stem cells to identify new genes required for reproduction and to define the role of these genes in human fertility and infertility,” said Dr. Clark, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, who recently led a study in this arena. “In vitro gametogenesis (IVG), another stem cell technology, is currently used in the research lab to understand causes of infertility.”

These stem cell-based embryo models, she said, can help researchers understand the first few days of embryo development after an embryo implants and be used to provide critical information on causes of early pregnancy loss or birth defects.

A version of this article appeared on Medscape.com.

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with cancer are at a high risk of venous thromboembolism (VTE)—in fact, it’s one of the leading causes of death in patients who receive systemic therapy for cancer. But as cancer treatment has evolved, have the incidence and risk of VTE changed too?

Researchers from Veterans Affairs Boston Healthcare System in Massachusetts conducted a study with 434,203 veterans to evaluate the pattern of VTE incidence over 16 years, focusing on the types of cancer, treatment, race and ethnicity, and other factors related to cancer-associated thrombosis (CAT).

In contrast with other large population studies, this study found the overall incidence of CAT remained largely stable over time. At 12 months, the incidence was 4.5%, with yearly trends ranging between 4.2% and 4.7%. “As expected,” the researchers say, the subset of patients receiving systemic therapy had a higher incidence of VTE at 12 months (7.7%) than did the overall cohort. The pattern was “particularly pronounced” in gynecologic, testicular, and kidney cancers, where the incidence of VTE was 2 to 3 times higher in the treated cohort compared with the overall cohort. 

Cancer type and diagnosis were the most statistically and clinically significant associations with CAT, with up to a 6-fold difference between cancer subtypes. The patients at the highest risk of VTE were those with pancreatic cancer and acute lymphoblastic leukemia.

Most studies have focused only on patients with solid tumors, but these researchers observed novel patterns among patients with hematologic neoplasms. Specifically, a higher incidence of VTE among patients with aggressive vs indolent leukemias and lymphomas. This trend, the researchers say, may be associated in part with catheter-related events.

Furthermore, the type of system treatment was associated with the risk of VTE, the researchers say, although to a lesser extent. Chemotherapy- and immunotherapy-based regimens had the highest risk of VTE, relative to no treatment. Targeted and endocrine therapy also carried a higher risk compared with no treatment but to a lesser degree.

The researchers found significant heterogeneity by race and ethnicity across cancer types. Non-Hispanic Black patients had about 20% higher risk of VTE compared with non-Hispanic White patients. Asian and Pacific Islander patients had about 20% lower risk compared with non-Hispanic White patients.

Male sex was also associated with VTE. However, “interestingly,” the researchers note, neighborhood-level socioeconomic factors and patients’ comorbidities were not associated with CAT but were associated with mortality.

Their results suggest that patient- and treatment-specific factors play a critical role in assessing the risk of CAT, and “ongoing efforts to identify these patterns are of utmost importance for risk stratification and prognostic assessment.”

Patients with cancer are at a high risk of venous thromboembolism (VTE)—in fact, it’s one of the leading causes of death in patients who receive systemic therapy for cancer. But as cancer treatment has evolved, have the incidence and risk of VTE changed too?

Researchers from Veterans Affairs Boston Healthcare System in Massachusetts conducted a study with 434,203 veterans to evaluate the pattern of VTE incidence over 16 years, focusing on the types of cancer, treatment, race and ethnicity, and other factors related to cancer-associated thrombosis (CAT).

In contrast with other large population studies, this study found the overall incidence of CAT remained largely stable over time. At 12 months, the incidence was 4.5%, with yearly trends ranging between 4.2% and 4.7%. “As expected,” the researchers say, the subset of patients receiving systemic therapy had a higher incidence of VTE at 12 months (7.7%) than did the overall cohort. The pattern was “particularly pronounced” in gynecologic, testicular, and kidney cancers, where the incidence of VTE was 2 to 3 times higher in the treated cohort compared with the overall cohort. 

Cancer type and diagnosis were the most statistically and clinically significant associations with CAT, with up to a 6-fold difference between cancer subtypes. The patients at the highest risk of VTE were those with pancreatic cancer and acute lymphoblastic leukemia.

Most studies have focused only on patients with solid tumors, but these researchers observed novel patterns among patients with hematologic neoplasms. Specifically, a higher incidence of VTE among patients with aggressive vs indolent leukemias and lymphomas. This trend, the researchers say, may be associated in part with catheter-related events.

Furthermore, the type of system treatment was associated with the risk of VTE, the researchers say, although to a lesser extent. Chemotherapy- and immunotherapy-based regimens had the highest risk of VTE, relative to no treatment. Targeted and endocrine therapy also carried a higher risk compared with no treatment but to a lesser degree.

The researchers found significant heterogeneity by race and ethnicity across cancer types. Non-Hispanic Black patients had about 20% higher risk of VTE compared with non-Hispanic White patients. Asian and Pacific Islander patients had about 20% lower risk compared with non-Hispanic White patients.

Male sex was also associated with VTE. However, “interestingly,” the researchers note, neighborhood-level socioeconomic factors and patients’ comorbidities were not associated with CAT but were associated with mortality.

Their results suggest that patient- and treatment-specific factors play a critical role in assessing the risk of CAT, and “ongoing efforts to identify these patterns are of utmost importance for risk stratification and prognostic assessment.”

Patients with cancer are at a high risk of venous thromboembolism (VTE)—in fact, it’s one of the leading causes of death in patients who receive systemic therapy for cancer. But as cancer treatment has evolved, have the incidence and risk of VTE changed too?

Researchers from Veterans Affairs Boston Healthcare System in Massachusetts conducted a study with 434,203 veterans to evaluate the pattern of VTE incidence over 16 years, focusing on the types of cancer, treatment, race and ethnicity, and other factors related to cancer-associated thrombosis (CAT).

In contrast with other large population studies, this study found the overall incidence of CAT remained largely stable over time. At 12 months, the incidence was 4.5%, with yearly trends ranging between 4.2% and 4.7%. “As expected,” the researchers say, the subset of patients receiving systemic therapy had a higher incidence of VTE at 12 months (7.7%) than did the overall cohort. The pattern was “particularly pronounced” in gynecologic, testicular, and kidney cancers, where the incidence of VTE was 2 to 3 times higher in the treated cohort compared with the overall cohort. 

Cancer type and diagnosis were the most statistically and clinically significant associations with CAT, with up to a 6-fold difference between cancer subtypes. The patients at the highest risk of VTE were those with pancreatic cancer and acute lymphoblastic leukemia.

Most studies have focused only on patients with solid tumors, but these researchers observed novel patterns among patients with hematologic neoplasms. Specifically, a higher incidence of VTE among patients with aggressive vs indolent leukemias and lymphomas. This trend, the researchers say, may be associated in part with catheter-related events.

Furthermore, the type of system treatment was associated with the risk of VTE, the researchers say, although to a lesser extent. Chemotherapy- and immunotherapy-based regimens had the highest risk of VTE, relative to no treatment. Targeted and endocrine therapy also carried a higher risk compared with no treatment but to a lesser degree.

The researchers found significant heterogeneity by race and ethnicity across cancer types. Non-Hispanic Black patients had about 20% higher risk of VTE compared with non-Hispanic White patients. Asian and Pacific Islander patients had about 20% lower risk compared with non-Hispanic White patients.

Male sex was also associated with VTE. However, “interestingly,” the researchers note, neighborhood-level socioeconomic factors and patients’ comorbidities were not associated with CAT but were associated with mortality.

Their results suggest that patient- and treatment-specific factors play a critical role in assessing the risk of CAT, and “ongoing efforts to identify these patterns are of utmost importance for risk stratification and prognostic assessment.”

As the number of female veterans continues to grow, the US Department of Veterans Affairs (VA) is adjusting by focusing more on breast/gynecological cancer and referring fewer cases to outside clinicians.

The VA’s effort reflects the reality that female veterans from the wars in Afghanistan and Iraq are approaching the ages—50s, 60s, and 70s—when cancer diagnoses become more common, said Sarah Colonna, MD, national medical director of breast oncology for VA's Breast and Gynecologic Oncology System of Excellence and an oncologist at the Huntsman Cancer Institute and Wahlen VA Medical Center in Salt Lake City, Utah. “This is preparation for the change that we know is coming.”

In response, the Association of VA Hematology/Oncology (AVAHO) is devoting a regional meeting in Tampa, Florida (July 29, 2023) to improving survivorship for patients with women’s cancers. “This meeting is designed to educate both cancer experts and primary care providers on the care of women who have already gone through breast and gynecological cancer treatment,” Colonna explained.

Adherence Challenges

Colonna will speak in a session about the importance of adherence to endocrine therapy. “When we prescribe endocrine therapy for breast cancer, we usually ask women to stay on it for 5 to 10 years, and sometimes that’s hard for them,” she said. “I’ll talk about tips and tricks to help women stay on endocrine therapy for the long haul because we know that is linked to better survival.”

Between two-thirds and three-quarters of women with breast cancer are advised to stay on endocrine drugs, she said, but the medications can be difficult to tolerate due to adverse effects such as hot flashes and sleep disturbances.

In addition, patients are often anxious about the medications. “Women are very leery of anything that changes or makes their hormones different,” Colonna noted. “They feel like it’s messing with something that is natural for them.”

Colonna urges colleagues to focus on their “soft skills,” the ability to absorb and validate the worries of patients. Instead of dismissing them, she said, focus on messages that acknowledge concerns but are also firm: “That’s real, that sucks. But we’ve got to do it.”

It’s also helpful to guide patients away from thinking that taking a pill every day means they’re sick. “I try to flip that paradigm: ‘You’re taking this pill every day because you have power over this thing that happened to you.’”

Education is also key, she said, so that patients “understand very clearly why this medication is important for them: It increases the chance of surviving breast cancer or it increases the chances that the cancer will never come back in your arm or in your breast. Then, whether they make a decision to take it or not, at least they’re making the choice with knowledge.”

As for adverse effects, Colonna said medications such as antidepressants and painkillers can relieve hot flashes, which can disturb sleep.

Identifying the best strategy to address adverse effects “requires keeping in frequent contact with the patient during the first 6 months of endocrine therapy, which are really critical,” she said. “Once they’ve been on it for a year, they can see the light at the end of the tunnel and hang in there even if they have adverse effects.”

Some guidelines suggest that no doctor visits are needed until the 6-month mark, but Colonna prefers to check in at the 4- to 6-week mark, even if it’s just via a phone call. Otherwise, “often they’ll stop taking the pill, and then you won’t know about it until you see them at 6 six months.” At that point, she said, a critical period for treatment has passed.

The Role of Nurse Navigators

In another session at the Tampa regional meeting, AVAHO president-elect Cindy Bowman, MSN, RN, OCN, will moderate a session about the role of nurse navigators in VA cancer care. She is the coordinator of the Cancer Care Navigation Program at the C. W. Bill Young VA Medical Center in Bay Pines, Florida.

“Veterans become survivors the day they’re diagnosed with cancer,” she said. Within the VA, cancer-care navigator teams developed over the past decade aim to help patients find their way forward through survivorship, she said, and nurses are crucial to the effort.

As Sharp and Scheid reported in a 2018 Journal Oncology Navigation Survivorship article, “research demonstrates that navigation can improve access to the cancer care system by addressing barriers, as well as facilitating quality care. The benefits of patient navigation for improving cancer patient outcomes is considerable.” McKenney and colleagues found that “patient navigation has been demonstrated to increase access to screening, shorten time to diagnostic resolution, and improve cancer outcomes, particularly in health disparity populations, such as women of color, rural populations, and poor women.” 

According to Bowman, “it has become standard practice to have nurse navigators be there each step of the way from a high suspicion of cancer to diagnosis and through the clinical workup into active treatment and survivorship.” Within the VA, she said, “the focus right now is to look at standardizing care that all VAs will be able to offer holistic, comprehensive cancer-care navigation teams.”

At the regional meeting, Bowman’s session will include updates from nurse navigators about helping patients through breast/gynecological cancer, abnormal mammograms, and survivorship.

Nurse navigators are typically the second medical professionals who talk to cancer patients after their physicians, Bowman said. The unique knowledge of oncology nurse navigators gives them invaluable insight into treatment plans and cancer drug regimens, she said.

“They’re able to sit down and discuss the actual cancer drug regimen with patients—what each of those drugs do, how they’re administered, the short-term and long-term side effects,” she said. “They have the knowledge about all aspects of cancer care that can really only come from somebody who’s specialty trained.”

Other sessions at the AVAHO regional meeting will highlight breast cancer and lymphedema, breast cancer and bone health; diet, exercise and cancer; sexual health for breast/gynecological cancer survivors; and imaging surveillance after diagnosis.

As the number of female veterans continues to grow, the US Department of Veterans Affairs (VA) is adjusting by focusing more on breast/gynecological cancer and referring fewer cases to outside clinicians.

The VA’s effort reflects the reality that female veterans from the wars in Afghanistan and Iraq are approaching the ages—50s, 60s, and 70s—when cancer diagnoses become more common, said Sarah Colonna, MD, national medical director of breast oncology for VA's Breast and Gynecologic Oncology System of Excellence and an oncologist at the Huntsman Cancer Institute and Wahlen VA Medical Center in Salt Lake City, Utah. “This is preparation for the change that we know is coming.”

In response, the Association of VA Hematology/Oncology (AVAHO) is devoting a regional meeting in Tampa, Florida (July 29, 2023) to improving survivorship for patients with women’s cancers. “This meeting is designed to educate both cancer experts and primary care providers on the care of women who have already gone through breast and gynecological cancer treatment,” Colonna explained.

Adherence Challenges

Colonna will speak in a session about the importance of adherence to endocrine therapy. “When we prescribe endocrine therapy for breast cancer, we usually ask women to stay on it for 5 to 10 years, and sometimes that’s hard for them,” she said. “I’ll talk about tips and tricks to help women stay on endocrine therapy for the long haul because we know that is linked to better survival.”

Between two-thirds and three-quarters of women with breast cancer are advised to stay on endocrine drugs, she said, but the medications can be difficult to tolerate due to adverse effects such as hot flashes and sleep disturbances.

In addition, patients are often anxious about the medications. “Women are very leery of anything that changes or makes their hormones different,” Colonna noted. “They feel like it’s messing with something that is natural for them.”

Colonna urges colleagues to focus on their “soft skills,” the ability to absorb and validate the worries of patients. Instead of dismissing them, she said, focus on messages that acknowledge concerns but are also firm: “That’s real, that sucks. But we’ve got to do it.”

It’s also helpful to guide patients away from thinking that taking a pill every day means they’re sick. “I try to flip that paradigm: ‘You’re taking this pill every day because you have power over this thing that happened to you.’”

Education is also key, she said, so that patients “understand very clearly why this medication is important for them: It increases the chance of surviving breast cancer or it increases the chances that the cancer will never come back in your arm or in your breast. Then, whether they make a decision to take it or not, at least they’re making the choice with knowledge.”

As for adverse effects, Colonna said medications such as antidepressants and painkillers can relieve hot flashes, which can disturb sleep.

Identifying the best strategy to address adverse effects “requires keeping in frequent contact with the patient during the first 6 months of endocrine therapy, which are really critical,” she said. “Once they’ve been on it for a year, they can see the light at the end of the tunnel and hang in there even if they have adverse effects.”

Some guidelines suggest that no doctor visits are needed until the 6-month mark, but Colonna prefers to check in at the 4- to 6-week mark, even if it’s just via a phone call. Otherwise, “often they’ll stop taking the pill, and then you won’t know about it until you see them at 6 six months.” At that point, she said, a critical period for treatment has passed.

The Role of Nurse Navigators

In another session at the Tampa regional meeting, AVAHO president-elect Cindy Bowman, MSN, RN, OCN, will moderate a session about the role of nurse navigators in VA cancer care. She is the coordinator of the Cancer Care Navigation Program at the C. W. Bill Young VA Medical Center in Bay Pines, Florida.

“Veterans become survivors the day they’re diagnosed with cancer,” she said. Within the VA, cancer-care navigator teams developed over the past decade aim to help patients find their way forward through survivorship, she said, and nurses are crucial to the effort.

As Sharp and Scheid reported in a 2018 Journal Oncology Navigation Survivorship article, “research demonstrates that navigation can improve access to the cancer care system by addressing barriers, as well as facilitating quality care. The benefits of patient navigation for improving cancer patient outcomes is considerable.” McKenney and colleagues found that “patient navigation has been demonstrated to increase access to screening, shorten time to diagnostic resolution, and improve cancer outcomes, particularly in health disparity populations, such as women of color, rural populations, and poor women.” 

According to Bowman, “it has become standard practice to have nurse navigators be there each step of the way from a high suspicion of cancer to diagnosis and through the clinical workup into active treatment and survivorship.” Within the VA, she said, “the focus right now is to look at standardizing care that all VAs will be able to offer holistic, comprehensive cancer-care navigation teams.”

At the regional meeting, Bowman’s session will include updates from nurse navigators about helping patients through breast/gynecological cancer, abnormal mammograms, and survivorship.

Nurse navigators are typically the second medical professionals who talk to cancer patients after their physicians, Bowman said. The unique knowledge of oncology nurse navigators gives them invaluable insight into treatment plans and cancer drug regimens, she said.

“They’re able to sit down and discuss the actual cancer drug regimen with patients—what each of those drugs do, how they’re administered, the short-term and long-term side effects,” she said. “They have the knowledge about all aspects of cancer care that can really only come from somebody who’s specialty trained.”

Other sessions at the AVAHO regional meeting will highlight breast cancer and lymphedema, breast cancer and bone health; diet, exercise and cancer; sexual health for breast/gynecological cancer survivors; and imaging surveillance after diagnosis.

As the number of female veterans continues to grow, the US Department of Veterans Affairs (VA) is adjusting by focusing more on breast/gynecological cancer and referring fewer cases to outside clinicians.

The VA’s effort reflects the reality that female veterans from the wars in Afghanistan and Iraq are approaching the ages—50s, 60s, and 70s—when cancer diagnoses become more common, said Sarah Colonna, MD, national medical director of breast oncology for VA's Breast and Gynecologic Oncology System of Excellence and an oncologist at the Huntsman Cancer Institute and Wahlen VA Medical Center in Salt Lake City, Utah. “This is preparation for the change that we know is coming.”

In response, the Association of VA Hematology/Oncology (AVAHO) is devoting a regional meeting in Tampa, Florida (July 29, 2023) to improving survivorship for patients with women’s cancers. “This meeting is designed to educate both cancer experts and primary care providers on the care of women who have already gone through breast and gynecological cancer treatment,” Colonna explained.

Adherence Challenges

Colonna will speak in a session about the importance of adherence to endocrine therapy. “When we prescribe endocrine therapy for breast cancer, we usually ask women to stay on it for 5 to 10 years, and sometimes that’s hard for them,” she said. “I’ll talk about tips and tricks to help women stay on endocrine therapy for the long haul because we know that is linked to better survival.”

Between two-thirds and three-quarters of women with breast cancer are advised to stay on endocrine drugs, she said, but the medications can be difficult to tolerate due to adverse effects such as hot flashes and sleep disturbances.

In addition, patients are often anxious about the medications. “Women are very leery of anything that changes or makes their hormones different,” Colonna noted. “They feel like it’s messing with something that is natural for them.”

Colonna urges colleagues to focus on their “soft skills,” the ability to absorb and validate the worries of patients. Instead of dismissing them, she said, focus on messages that acknowledge concerns but are also firm: “That’s real, that sucks. But we’ve got to do it.”

It’s also helpful to guide patients away from thinking that taking a pill every day means they’re sick. “I try to flip that paradigm: ‘You’re taking this pill every day because you have power over this thing that happened to you.’”

Education is also key, she said, so that patients “understand very clearly why this medication is important for them: It increases the chance of surviving breast cancer or it increases the chances that the cancer will never come back in your arm or in your breast. Then, whether they make a decision to take it or not, at least they’re making the choice with knowledge.”

As for adverse effects, Colonna said medications such as antidepressants and painkillers can relieve hot flashes, which can disturb sleep.

Identifying the best strategy to address adverse effects “requires keeping in frequent contact with the patient during the first 6 months of endocrine therapy, which are really critical,” she said. “Once they’ve been on it for a year, they can see the light at the end of the tunnel and hang in there even if they have adverse effects.”

Some guidelines suggest that no doctor visits are needed until the 6-month mark, but Colonna prefers to check in at the 4- to 6-week mark, even if it’s just via a phone call. Otherwise, “often they’ll stop taking the pill, and then you won’t know about it until you see them at 6 six months.” At that point, she said, a critical period for treatment has passed.

The Role of Nurse Navigators

In another session at the Tampa regional meeting, AVAHO president-elect Cindy Bowman, MSN, RN, OCN, will moderate a session about the role of nurse navigators in VA cancer care. She is the coordinator of the Cancer Care Navigation Program at the C. W. Bill Young VA Medical Center in Bay Pines, Florida.

“Veterans become survivors the day they’re diagnosed with cancer,” she said. Within the VA, cancer-care navigator teams developed over the past decade aim to help patients find their way forward through survivorship, she said, and nurses are crucial to the effort.

As Sharp and Scheid reported in a 2018 Journal Oncology Navigation Survivorship article, “research demonstrates that navigation can improve access to the cancer care system by addressing barriers, as well as facilitating quality care. The benefits of patient navigation for improving cancer patient outcomes is considerable.” McKenney and colleagues found that “patient navigation has been demonstrated to increase access to screening, shorten time to diagnostic resolution, and improve cancer outcomes, particularly in health disparity populations, such as women of color, rural populations, and poor women.” 

According to Bowman, “it has become standard practice to have nurse navigators be there each step of the way from a high suspicion of cancer to diagnosis and through the clinical workup into active treatment and survivorship.” Within the VA, she said, “the focus right now is to look at standardizing care that all VAs will be able to offer holistic, comprehensive cancer-care navigation teams.”

At the regional meeting, Bowman’s session will include updates from nurse navigators about helping patients through breast/gynecological cancer, abnormal mammograms, and survivorship.

Nurse navigators are typically the second medical professionals who talk to cancer patients after their physicians, Bowman said. The unique knowledge of oncology nurse navigators gives them invaluable insight into treatment plans and cancer drug regimens, she said.

“They’re able to sit down and discuss the actual cancer drug regimen with patients—what each of those drugs do, how they’re administered, the short-term and long-term side effects,” she said. “They have the knowledge about all aspects of cancer care that can really only come from somebody who’s specialty trained.”

Other sessions at the AVAHO regional meeting will highlight breast cancer and lymphedema, breast cancer and bone health; diet, exercise and cancer; sexual health for breast/gynecological cancer survivors; and imaging surveillance after diagnosis.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Higher rates of cervical cancer screening are associated with an increased risk of preterm delivery (PTD) in young nulliparous women aged 18-24 years, a large population-based study found.

For each additional recommended screening before childbirth, there was a direct increase in absolute PTD risk of 0.073 (95% confidence interval, 0.026-0.120), according to a study led by Rebecca A. Bromley-Dulfano, MS, an MD candidate at Stanford (Calif.) University and a PhD candidate in health policy at Harvard University, Cambridge, Mass.

courtesy Ms. Bromley-Dulfano

There was no significant change in very preterm delivery (VPTD) risk, but mothers with hypertension or diabetes were at higher PTD risk.

Women in this younger age group are more prone to PTD. According to the study’s estimate, an additional 73 PTDs per 100,000 women could be expected for every 1 additional recommended screening before childbirth. For the year 2018, that translated to an estimated 1,348 PTDs that could have been averted, with reduced screening requirements (3% relative reduction).

“If you screen someone for cervical cancer and find a cervical lesion, the possible next steps can include a biopsy and an excisional procedure to remove the lesion,” Ms. Bromley-Dulfano explained, “and these procedures which remove a small (mostly diseased) part of the cervix have been shown to slightly increase the risk of PTD. Particularly in young individuals with a cervix who are known to have high rates of lesion regression and who have more potential childbearing years ahead of them, it is important to weigh the oncological benefits with the adverse birth outcome risks.” 

Young women are more likely to have false-positive results on Papanicolaou tests and lesion regression within 2 years but may undergo unnecessary treatment, the authors noted.

Cervical excision procedures have previously been associated in clinical trials with an increase in PTB risk.

In their 2017 decision model in a fictive cohort, for example, Kamphuis and colleagues found the most intensive screening program was associated with an increase in maternal life years of 9%, a decrease in cervical cancer incidence of 67%, and a decrease in cervical cancer deaths of 75%. But those gains came at the cost of 250% more preterm births, compared with the least intensive program.

“These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies,” the researchers wrote.

While the optimal screening strategy must trade off the oncologic benefits of cancer detection against the neonatal harms of overtreatment, the ideal age of cervical cancer screening onset and frequency remain uncertain, the authors noted. Recent American Cancer Society guidelines recommending less frequent screening for some diverge from those of other societies.

“The first and foremost priority is for gynecologists to continue to have individualized conversations with patients about all of the benefits and risks of procedures that patients undergo and to understand the benefits and risks influencing screening guidelines,” Ms. Bromley-Dulfano said.
 

Cross-sectional study

The study used data from the Centers for Disease Control and Prevention’s National Center for Health Statistics to analyze associations between cervical cancer screening guidelines and birth outcomes women who had a singleton nulliparous birth from 19916 to 2018. Gestational age and maternal characteristics were drawn from birth certificates.

The mean age of the 11,333,151 multiracial cohort of women was 20.9 years, and 6.8% had hypertension or diabetes. The mean number of guideline-recommended screenings by time of childbirth was 2.4. Overall, PTD and very PTD occurred in 1,140,490 individuals (10.1%) and 333,040 (2.9%) of births, respectively.

Those with hypertension or diabetes had a somewhat higher PTD risk: 0.26% (95% CI, 0.11-0.4) versus 0.06% (95% CI, 0.01-0.10; Wald test, P < .001).

courtesy Northwell Health

Offering an outsider’s perspective on the analysis, ob.gyn. Fidel A. Valea, MD, director of gynecologic oncology at the Northwell Health Cancer Institute in New Hyde Park, N.Y., urged caution in drawing conclusions from large population analyses such as this.

“This study had over 11 million data points. Often these large numbers will show statistical differences that are not clinically significant,” he said in an interview. He noted that while small studies have shown a possible impact of frequent Pap tests on cervical function, “this is not 100% proven. Research from Texas showed that screening made a difference only in cases of dysplasia.”

Dr. Valea also noted that screening guidelines have already changed over the lengthy time span of the study and do reflect the concerns of the study authors.

“We know that the HPV virus is cleared more readily by young women than older women and so we have made adjustments and test them less frequently and we test them less early.” He added that conservative options are recommended even in the case of dysplasia.

In defense of the Pap smear test, he added: “It has virtually wiped out cervical cancer in the U.S., bringing it from No. 1 to No. 13.” While broadening HPV vaccination programs may impact guidelines in the future, “vaccination is still in its infancy. We have to wait until women have lived long to enough to see an impact.”

As to why this age group is more vulnerable to PTD, Dr. Valea said, “It’s likely multifactorial, with lifestyle and other factors involved.” Although based on U.S. data, the authors said their results may be useful for other public health entities, particularly in countries where cervical cancer is considerably more prevalent.

This work received no specific funding. The authors and Dr. Valea disclosed no competing interests.

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]