Men's Health

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

BOSTON — An investigational male contraceptive gel suppresses sperm more rapidly than previous products in development, new data suggested.

The product, 8 mg segesterone acetate (Nestorone) combined with 74 mg testosterone (“NesT”) is a gel that a man applies daily to both shoulders. The progesterone blocks spermatogenesis, and the testosterone restores blood levels to maintain sexual function. It is under development by the National Institute of Child Health and Human Development (NICHD) in collaboration with the Population Council, the Los Angeles Biomedical Research Institute, and the University of Washington School of Medicine.

Currently, the only available male contraceptives are vasectomy, which isn’t easily reversible, and condoms, which have a high failure rate. Previous attempts to develop a “male pill” have been unsuccessful for a variety of reasons, but so far, this product appears effective and safe, Diana Blithe, PhD, chief of the Contraceptive Development Program at NICHD, said at a press briefing held on June 2, 2024, during the annual meeting of the Endocrine Society.

“It’s been a long time coming. … Men need and want more contraceptive options such as an effective reversible method,” she told this news organization.

New phase 2b data show that among 222 couples in which the man initially had normal (> 15 million/mL) sperm counts, the median time to suppression (< 1 million/mL) was less than 8 weeks with NesT compared with 9-15 weeks seen in previous trials of injected male hormonal contraceptives. Nearly all (86%) had achieved suppression by 15 weeks.

After two consecutive counts of < 1 million/mL, the couples entered the trial’s ongoing 2-year efficacy phase. There have been no major safety concerns thus far, but “we need more data,” Dr. Blithe noted.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “certainly, I think it’s a big advance on what we have so far. … I think it’s showing great promise.”

Dr. Hayes did caution, though, that “with real-world use, daily application of a gel might be a bit more challenging than taking an injection…an injection is more consistent. With a gel, patients might forget or shower it off. But I don’t think 1 day of interruption would be a significant thing.”

Transference of the topical to a partner or a child is another potential concern, Dr. Hayes noted, although this is true of current testosterone gel products as well. During the briefing, Dr. Blithe said that this issue is why the product is recommended to be placed on the upper arms rather than the abdomen or another spot more likely to come into contact with another person. Also, in the trial, men were instructed to wear shirts during intercourse.

Regarding the rapidity of sperm suppression, Dr. Hayes said, “It’s surprising. It looks great as a reversible contraceptive. … Normally, you think of the life cycle of the sperm being about 72 days. So to see 50% suppression by 8 weeks, and then 85%-90% by 15 weeks, that’s very rapid. It may be that the progesterone that they’re using is very potent. Progestins can have some negative effects on lipids and mood. We didn’t really see the safety data in this presentation. So that will be interesting to see.”

During the briefing, Dr. Blithe said that the phase 2b trial is expected to finish by the end of this year, and in the meantime, the researchers are communicating with the US Food and Drug Administration about the design of a phase 3 trial because this is an unprecedented area. “They don’t have guidelines yet. They’ll need to develop them first.”

Dr. Blithe has been the NICHD principal investigator on cooperative research and development agreements with HRA Pharma and Daré Bioscience. Dr. Hayes had no disclosures.

A version of this article appeared on Medscape.com .

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A relatively high percentage of men in their 70s and 80s, as well those determined to have a limited life expectancy, report receiving prostate cancer screening, despite recommendations against screening for men in those age groups.

In its most recent guidance, the US Preventive Services Task Force (USPSTF) revised a previous 2012 recommendation against routine screening for prostate cancer to instead endorse individual decision-making for men aged 55 to 69 years (grade C).

In the update guidance, which was published in 2018, the task force still recommended against PSA-based screening for prostate cancer in men 70 years and older (grade D) due to a range of potential risks and harms. Guidelines from the American Urological Association and American Cancer Society have echoed that recommendation, in general agreement that men over the age of 70 or with limited life expectancy show little benefit from the screening.

To take a closer look at how commonly men are being screened for prostate cancer, based not only on their age but their estimated life expectancy, Kevin H. Kensler, ScD, of Weill Cornell Medicine, and colleagues conducted a cross-sectional study using data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS).

“Our findings indicate that many males aged 70 years and older or those with a high risk of death within 10 years undergo prostate cancer screening despite the recommendation against screening in these populations by current guidelines,” the authors wrote in their paper, published in JAMA Network Open. The results underscore that “enhancements to the shared decision-making process are needed to ensure that older males who undergo screening are those who may potentially benefit,” they noted.

For the study, the authors identified 57,397 men aged 60 and older without a history of prostate cancer who reported undergoing a screening PSA test in the prior 2 years.

Using a risk factor system, mortality risk was estimated based on the scales ranging from 5.5 or less to 10.0 or greater, corresponding to the estimated 10-year mortality of less than 30% to 71% or more, respectively.

Of the men, 19.2% were aged 70 to 74 years, 13.0% were aged 75 to 79 years, and 12.3% were aged 80 years or older. The rest were 69 years or younger.

While the estimated 2-year prostate cancer screening rates were 36.3% among those aged 60 to 64 years and 42.8% for those 65 to 69 years, the rates were even higher, at 47.1%, among those aged 70 to 74 years, and similar, at 42.7%, in the 75 to 79 years of age range. Among those aged 80 years and older, 30.4% had been screened.

While the screening frequency was 43.4% among males with the greatest estimated life expectancy, a fair percentage of men, 30.4%, with the lowest life expectancy, indicative of a 71% or greater risk of death within 10 years, received prostate cancer screening.

In fact, among those with lowest life expectancy, the screening rates were greater than 20% in all age groups.
 

Screening in Older Age: Benefit in Reducing Mortality Low

Autopsy research indicates that, in fact, as many as 50% of men do have prostate cancer at age 80; however, many of those tumors are low-risk and unlikely to affect the health of the men.

If detected early, as is the intention of screening, prostate cancer can take years to advance and the likelihood of receiving any mortality benefit from continued screening in older age is low.

Furthermore, screening in older age can have implications, including a higher risk of complications following a false positive prostate biopsy that may not have been necessary in the first place, the authors explained.

“Given the long natural history of prostate cancer and lead time associated with PSA-based screening, these males [aged 70 and older or with a high risk of death within 10 years] have a low likelihood of receiving any mortality benefit from continued screening,” the authors reported.

“Yet they face the potential harms of overdiagnosis, such as complications after prostate biopsy for a false-positive screening and psychological stress associated with a cancer diagnosis.”
 

Guideline Confusion, Habit, Among Reasons for Continued Screening

Among key reasons for the continued screening of men well into old age is the fluctuating history of the guidelines, Dr. Kensler said in an interview.

“There has been considerable variation in prostate cancer screening guidelines over time and across organizations that make screening recommendations, and this has inevitably led to some confusion among clinicians,” he explained.

However, the evidence of a lack of benefit over the age of 70 is strong enough that not performing PSA-based screening among men ages 70 or older is a Healthcare Effectiveness Data and Information Set (HEDIS) measure for quality of care, he noted.

Nevertheless, “I think the trends we found in our analysis reflect that it is difficult for patients and providers to stop providing screening once they have already started it,” Dr. Kensler said.

Another motivator may be an inclination by clinicians to err on the side of caution, he added.

“For clinicians, although they may be aware of the guidelines, they may perhaps fear that they will not have offered screening to one of the older individuals who would have benefited from it even though they recognize that most would not,” Dr. Kensler noted.

Too often, however, such screenings “can lead to a cascade of other events that end up harming the patient without extending their lifespan,” he said.
 

Difficult Discussions

Complicating matters is the task of informing patients that due to their life expectancy, screening is considered to not likely be worthwhile — which may not be an easy discussion.

“For patients, hearing that they are at a stage of life where they may not benefit from screening is an unpleasant message to receive,” Dr. Kensler said.

“Having an in-depth conversation on this topic is also difficult given the many other health topics that clinicians and patients must cover during a visit.”

Ultimately, “these and other factors lead to inertia, where it is easier to stick to the status quo of continuing screening.”

The challenges underscore the need for improvements to the shared decision-making process to make sure that older men who do undergo prostrate screening will benefit, Dr. Kensler argued.

“If the guidelines are going to recommend shared decision-making, we need to provide tools to help patients and clinicians navigate these potentially difficult conversations.
 

Life Expectancy Uncertainties

Commenting on the research in an interview, Kyle Richards, MD, associate professor with the Department of Urology at the University of Wisconsin School of Medicine and Public Health, in Madison, noted that, “while most urology experts agree that we should not screen for prostate cancer in men with less than 5-10 years life expectancy, the challenge is deciding which patients have a more limited life expectancy.” 

Tools and calculators are available to try to calculate life expectancy, “but they can be cumbersome and difficult to incorporate into clinical practice,” he added.

Indeed, the difficulty in accurately estimating life expectancy is also a limitation of the study, he noted.

“The challenge with a study like this is it is very difficult to accurately estimate life expectancy,” he said. “It is easy to pick a cut point (i.e. age 70) but it is very difficult to calculate one’s life expectancy from survey data alone.” 

Another limitation is that “screening PSA testing implies that the patient is not having any symptoms, and we do not know from this study if any of these men were getting PSA checks due to some urinary symptoms or other issues,” Dr. Richards added.

“So, while the study does raise some concern about screening PSA in older men, the data source makes it quite difficult to home in on this question.”

When it can be estimated, life expectancy can indeed provide a more useful guide in assessing the options if a patient is found to have prostate cancer, Dr. Richards noted.

“If a patient has a 5- to 10-year life expectancy, and they are diagnosed with a clinically significant prostate cancer, they absolutely may still benefit from treatment,” he said.

“If they have a clinically significant prostate cancer that is unrecognized, it could metastasize and cause symptoms or lead to death, as roughly 30,000 men die from prostate cancer each year in the USA.”

However, “if a patient has a limited life expectancy of less than 5 to 10 years, don’t screen for prostate cancer,” he advised. Proper guidance should furthermore be made loud and clear in guideline recommendations.

“I do think the USPSTF and AUA need to be the primary voices educating primary care and patients regarding prostate cancer screening,” Dr. Richards said.

“We need to be smart about whom to screen, when to screen, and how often to screen. And this message needs to be heard by the primary care providers that perform the screening.”

The study was supported by the Sandra and Edward Meyer Cancer Center and a grant from the National Cancer Institute of the National Institutes of Health.

Dr. Kensler and Dr. Richards had no disclosures to report.

A relatively high percentage of men in their 70s and 80s, as well those determined to have a limited life expectancy, report receiving prostate cancer screening, despite recommendations against screening for men in those age groups.

In its most recent guidance, the US Preventive Services Task Force (USPSTF) revised a previous 2012 recommendation against routine screening for prostate cancer to instead endorse individual decision-making for men aged 55 to 69 years (grade C).

In the update guidance, which was published in 2018, the task force still recommended against PSA-based screening for prostate cancer in men 70 years and older (grade D) due to a range of potential risks and harms. Guidelines from the American Urological Association and American Cancer Society have echoed that recommendation, in general agreement that men over the age of 70 or with limited life expectancy show little benefit from the screening.

To take a closer look at how commonly men are being screened for prostate cancer, based not only on their age but their estimated life expectancy, Kevin H. Kensler, ScD, of Weill Cornell Medicine, and colleagues conducted a cross-sectional study using data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS).

“Our findings indicate that many males aged 70 years and older or those with a high risk of death within 10 years undergo prostate cancer screening despite the recommendation against screening in these populations by current guidelines,” the authors wrote in their paper, published in JAMA Network Open. The results underscore that “enhancements to the shared decision-making process are needed to ensure that older males who undergo screening are those who may potentially benefit,” they noted.

For the study, the authors identified 57,397 men aged 60 and older without a history of prostate cancer who reported undergoing a screening PSA test in the prior 2 years.

Using a risk factor system, mortality risk was estimated based on the scales ranging from 5.5 or less to 10.0 or greater, corresponding to the estimated 10-year mortality of less than 30% to 71% or more, respectively.

Of the men, 19.2% were aged 70 to 74 years, 13.0% were aged 75 to 79 years, and 12.3% were aged 80 years or older. The rest were 69 years or younger.

While the estimated 2-year prostate cancer screening rates were 36.3% among those aged 60 to 64 years and 42.8% for those 65 to 69 years, the rates were even higher, at 47.1%, among those aged 70 to 74 years, and similar, at 42.7%, in the 75 to 79 years of age range. Among those aged 80 years and older, 30.4% had been screened.

While the screening frequency was 43.4% among males with the greatest estimated life expectancy, a fair percentage of men, 30.4%, with the lowest life expectancy, indicative of a 71% or greater risk of death within 10 years, received prostate cancer screening.

In fact, among those with lowest life expectancy, the screening rates were greater than 20% in all age groups.
 

Screening in Older Age: Benefit in Reducing Mortality Low

Autopsy research indicates that, in fact, as many as 50% of men do have prostate cancer at age 80; however, many of those tumors are low-risk and unlikely to affect the health of the men.

If detected early, as is the intention of screening, prostate cancer can take years to advance and the likelihood of receiving any mortality benefit from continued screening in older age is low.

Furthermore, screening in older age can have implications, including a higher risk of complications following a false positive prostate biopsy that may not have been necessary in the first place, the authors explained.

“Given the long natural history of prostate cancer and lead time associated with PSA-based screening, these males [aged 70 and older or with a high risk of death within 10 years] have a low likelihood of receiving any mortality benefit from continued screening,” the authors reported.

“Yet they face the potential harms of overdiagnosis, such as complications after prostate biopsy for a false-positive screening and psychological stress associated with a cancer diagnosis.”
 

Guideline Confusion, Habit, Among Reasons for Continued Screening

Among key reasons for the continued screening of men well into old age is the fluctuating history of the guidelines, Dr. Kensler said in an interview.

“There has been considerable variation in prostate cancer screening guidelines over time and across organizations that make screening recommendations, and this has inevitably led to some confusion among clinicians,” he explained.

However, the evidence of a lack of benefit over the age of 70 is strong enough that not performing PSA-based screening among men ages 70 or older is a Healthcare Effectiveness Data and Information Set (HEDIS) measure for quality of care, he noted.

Nevertheless, “I think the trends we found in our analysis reflect that it is difficult for patients and providers to stop providing screening once they have already started it,” Dr. Kensler said.

Another motivator may be an inclination by clinicians to err on the side of caution, he added.

“For clinicians, although they may be aware of the guidelines, they may perhaps fear that they will not have offered screening to one of the older individuals who would have benefited from it even though they recognize that most would not,” Dr. Kensler noted.

Too often, however, such screenings “can lead to a cascade of other events that end up harming the patient without extending their lifespan,” he said.
 

Difficult Discussions

Complicating matters is the task of informing patients that due to their life expectancy, screening is considered to not likely be worthwhile — which may not be an easy discussion.

“For patients, hearing that they are at a stage of life where they may not benefit from screening is an unpleasant message to receive,” Dr. Kensler said.

“Having an in-depth conversation on this topic is also difficult given the many other health topics that clinicians and patients must cover during a visit.”

Ultimately, “these and other factors lead to inertia, where it is easier to stick to the status quo of continuing screening.”

The challenges underscore the need for improvements to the shared decision-making process to make sure that older men who do undergo prostrate screening will benefit, Dr. Kensler argued.

“If the guidelines are going to recommend shared decision-making, we need to provide tools to help patients and clinicians navigate these potentially difficult conversations.
 

Life Expectancy Uncertainties

Commenting on the research in an interview, Kyle Richards, MD, associate professor with the Department of Urology at the University of Wisconsin School of Medicine and Public Health, in Madison, noted that, “while most urology experts agree that we should not screen for prostate cancer in men with less than 5-10 years life expectancy, the challenge is deciding which patients have a more limited life expectancy.” 

Tools and calculators are available to try to calculate life expectancy, “but they can be cumbersome and difficult to incorporate into clinical practice,” he added.

Indeed, the difficulty in accurately estimating life expectancy is also a limitation of the study, he noted.

“The challenge with a study like this is it is very difficult to accurately estimate life expectancy,” he said. “It is easy to pick a cut point (i.e. age 70) but it is very difficult to calculate one’s life expectancy from survey data alone.” 

Another limitation is that “screening PSA testing implies that the patient is not having any symptoms, and we do not know from this study if any of these men were getting PSA checks due to some urinary symptoms or other issues,” Dr. Richards added.

“So, while the study does raise some concern about screening PSA in older men, the data source makes it quite difficult to home in on this question.”

When it can be estimated, life expectancy can indeed provide a more useful guide in assessing the options if a patient is found to have prostate cancer, Dr. Richards noted.

“If a patient has a 5- to 10-year life expectancy, and they are diagnosed with a clinically significant prostate cancer, they absolutely may still benefit from treatment,” he said.

“If they have a clinically significant prostate cancer that is unrecognized, it could metastasize and cause symptoms or lead to death, as roughly 30,000 men die from prostate cancer each year in the USA.”

However, “if a patient has a limited life expectancy of less than 5 to 10 years, don’t screen for prostate cancer,” he advised. Proper guidance should furthermore be made loud and clear in guideline recommendations.

“I do think the USPSTF and AUA need to be the primary voices educating primary care and patients regarding prostate cancer screening,” Dr. Richards said.

“We need to be smart about whom to screen, when to screen, and how often to screen. And this message needs to be heard by the primary care providers that perform the screening.”

The study was supported by the Sandra and Edward Meyer Cancer Center and a grant from the National Cancer Institute of the National Institutes of Health.

Dr. Kensler and Dr. Richards had no disclosures to report.

A relatively high percentage of men in their 70s and 80s, as well those determined to have a limited life expectancy, report receiving prostate cancer screening, despite recommendations against screening for men in those age groups.

In its most recent guidance, the US Preventive Services Task Force (USPSTF) revised a previous 2012 recommendation against routine screening for prostate cancer to instead endorse individual decision-making for men aged 55 to 69 years (grade C).

In the update guidance, which was published in 2018, the task force still recommended against PSA-based screening for prostate cancer in men 70 years and older (grade D) due to a range of potential risks and harms. Guidelines from the American Urological Association and American Cancer Society have echoed that recommendation, in general agreement that men over the age of 70 or with limited life expectancy show little benefit from the screening.

To take a closer look at how commonly men are being screened for prostate cancer, based not only on their age but their estimated life expectancy, Kevin H. Kensler, ScD, of Weill Cornell Medicine, and colleagues conducted a cross-sectional study using data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS).

“Our findings indicate that many males aged 70 years and older or those with a high risk of death within 10 years undergo prostate cancer screening despite the recommendation against screening in these populations by current guidelines,” the authors wrote in their paper, published in JAMA Network Open. The results underscore that “enhancements to the shared decision-making process are needed to ensure that older males who undergo screening are those who may potentially benefit,” they noted.

For the study, the authors identified 57,397 men aged 60 and older without a history of prostate cancer who reported undergoing a screening PSA test in the prior 2 years.

Using a risk factor system, mortality risk was estimated based on the scales ranging from 5.5 or less to 10.0 or greater, corresponding to the estimated 10-year mortality of less than 30% to 71% or more, respectively.

Of the men, 19.2% were aged 70 to 74 years, 13.0% were aged 75 to 79 years, and 12.3% were aged 80 years or older. The rest were 69 years or younger.

While the estimated 2-year prostate cancer screening rates were 36.3% among those aged 60 to 64 years and 42.8% for those 65 to 69 years, the rates were even higher, at 47.1%, among those aged 70 to 74 years, and similar, at 42.7%, in the 75 to 79 years of age range. Among those aged 80 years and older, 30.4% had been screened.

While the screening frequency was 43.4% among males with the greatest estimated life expectancy, a fair percentage of men, 30.4%, with the lowest life expectancy, indicative of a 71% or greater risk of death within 10 years, received prostate cancer screening.

In fact, among those with lowest life expectancy, the screening rates were greater than 20% in all age groups.
 

Screening in Older Age: Benefit in Reducing Mortality Low

Autopsy research indicates that, in fact, as many as 50% of men do have prostate cancer at age 80; however, many of those tumors are low-risk and unlikely to affect the health of the men.

If detected early, as is the intention of screening, prostate cancer can take years to advance and the likelihood of receiving any mortality benefit from continued screening in older age is low.

Furthermore, screening in older age can have implications, including a higher risk of complications following a false positive prostate biopsy that may not have been necessary in the first place, the authors explained.

“Given the long natural history of prostate cancer and lead time associated with PSA-based screening, these males [aged 70 and older or with a high risk of death within 10 years] have a low likelihood of receiving any mortality benefit from continued screening,” the authors reported.

“Yet they face the potential harms of overdiagnosis, such as complications after prostate biopsy for a false-positive screening and psychological stress associated with a cancer diagnosis.”
 

Guideline Confusion, Habit, Among Reasons for Continued Screening

Among key reasons for the continued screening of men well into old age is the fluctuating history of the guidelines, Dr. Kensler said in an interview.

“There has been considerable variation in prostate cancer screening guidelines over time and across organizations that make screening recommendations, and this has inevitably led to some confusion among clinicians,” he explained.

However, the evidence of a lack of benefit over the age of 70 is strong enough that not performing PSA-based screening among men ages 70 or older is a Healthcare Effectiveness Data and Information Set (HEDIS) measure for quality of care, he noted.

Nevertheless, “I think the trends we found in our analysis reflect that it is difficult for patients and providers to stop providing screening once they have already started it,” Dr. Kensler said.

Another motivator may be an inclination by clinicians to err on the side of caution, he added.

“For clinicians, although they may be aware of the guidelines, they may perhaps fear that they will not have offered screening to one of the older individuals who would have benefited from it even though they recognize that most would not,” Dr. Kensler noted.

Too often, however, such screenings “can lead to a cascade of other events that end up harming the patient without extending their lifespan,” he said.
 

Difficult Discussions

Complicating matters is the task of informing patients that due to their life expectancy, screening is considered to not likely be worthwhile — which may not be an easy discussion.

“For patients, hearing that they are at a stage of life where they may not benefit from screening is an unpleasant message to receive,” Dr. Kensler said.

“Having an in-depth conversation on this topic is also difficult given the many other health topics that clinicians and patients must cover during a visit.”

Ultimately, “these and other factors lead to inertia, where it is easier to stick to the status quo of continuing screening.”

The challenges underscore the need for improvements to the shared decision-making process to make sure that older men who do undergo prostrate screening will benefit, Dr. Kensler argued.

“If the guidelines are going to recommend shared decision-making, we need to provide tools to help patients and clinicians navigate these potentially difficult conversations.
 

Life Expectancy Uncertainties

Commenting on the research in an interview, Kyle Richards, MD, associate professor with the Department of Urology at the University of Wisconsin School of Medicine and Public Health, in Madison, noted that, “while most urology experts agree that we should not screen for prostate cancer in men with less than 5-10 years life expectancy, the challenge is deciding which patients have a more limited life expectancy.” 

Tools and calculators are available to try to calculate life expectancy, “but they can be cumbersome and difficult to incorporate into clinical practice,” he added.

Indeed, the difficulty in accurately estimating life expectancy is also a limitation of the study, he noted.

“The challenge with a study like this is it is very difficult to accurately estimate life expectancy,” he said. “It is easy to pick a cut point (i.e. age 70) but it is very difficult to calculate one’s life expectancy from survey data alone.” 

Another limitation is that “screening PSA testing implies that the patient is not having any symptoms, and we do not know from this study if any of these men were getting PSA checks due to some urinary symptoms or other issues,” Dr. Richards added.

“So, while the study does raise some concern about screening PSA in older men, the data source makes it quite difficult to home in on this question.”

When it can be estimated, life expectancy can indeed provide a more useful guide in assessing the options if a patient is found to have prostate cancer, Dr. Richards noted.

“If a patient has a 5- to 10-year life expectancy, and they are diagnosed with a clinically significant prostate cancer, they absolutely may still benefit from treatment,” he said.

“If they have a clinically significant prostate cancer that is unrecognized, it could metastasize and cause symptoms or lead to death, as roughly 30,000 men die from prostate cancer each year in the USA.”

However, “if a patient has a limited life expectancy of less than 5 to 10 years, don’t screen for prostate cancer,” he advised. Proper guidance should furthermore be made loud and clear in guideline recommendations.

“I do think the USPSTF and AUA need to be the primary voices educating primary care and patients regarding prostate cancer screening,” Dr. Richards said.

“We need to be smart about whom to screen, when to screen, and how often to screen. And this message needs to be heard by the primary care providers that perform the screening.”

The study was supported by the Sandra and Edward Meyer Cancer Center and a grant from the National Cancer Institute of the National Institutes of Health.

Dr. Kensler and Dr. Richards had no disclosures to report.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

The medication vibegron led to improvements in symptoms of overactive bladder and overall quality of life in men undergoing treatment for benign prostatic hyperplasia, according to findings from a phase 3 trial presented at the annual meeting of the American Urological Association (AUA) and data published in the Journal of Urology.

“Vibegron was associated with significant reductions in daily micturition and urgency episodes, as well as our secondary endpoints,” David R. Staskin, MD, an associate professor of urology at Tufts University School of Medicine in Boston, told attendees. “Symptoms really did improve compared to placebo as early as week 2.”

Vibegron is a selective beta-3 adrenergic receptor agonist approved in 2020 by the US Food and Drug Administration for the treatment of overactive bladder.

However, treating overactive bladder symptoms in patients undergoing benign prostatic hyperplasia treatment is more complex because benign prostatic hyperplasia itself can contribute to overactive bladder symptoms, said Kara Watts, MD, an associate professor of urology at Montefiore Einstein in New York City, who was not involved in the new research.

“Management of overactive bladder in this setting may require treatment of benign prostatic hyperplasia as well, but a discussion of the relationship between benign prostatic hyperplasia and overactive bladder symptoms is important,” Dr. Watts told this news organization. “Beyond consideration of treatment for benign prostatic hyperplasia — which can be in the form of medications or surgeries to reduce the size of the prostate — treatment of overactive bladder can include behavioral modification,” such as avoiding bladder irritants, timed voiding, managing constipation, and nighttime liquid restriction,” as well as “medications, percutaneous tibial nerve stimulation, and occasionally more invasive options.”

Vibegron “represents a very attractive and effective pharmaceutical management option for overactive bladder,” both in patients with and without benign prostatic hyperplasia, Dr. Watts said. “It has a favorable side-effect profile compared to other oral agents that can be prescribed for overactive bladder, such as anticholinergics, and also has the added benefit of a much lower risk of urinary retention in comparison to most other oral agents.”

Among 1104 men at least 45 years old who were undergoing treatment for benign prostatic hyperplasia and had symptoms of overactive bladder, 538 received 75 mg of vibegron and 542 received a placebo. The men in the vibegron group showed 2.04 fewer mean daily urinations at 12 weeks and 2.2 fewer at 24 weeks compared to 1.3 fewer at both 12 and 24 weeks for men in the placebo group (P < .0001), according to the researchers.

The drug also reduced urgency of urination. Mean daily episodes of urgency were 2.88 fewer at 12 weeks and 3.07 fewer at 24 weeks in the vibegron group compared to 1.93 and 2.17 fewer, respectively, in the placebo group (P < .0001).

In secondary endpoints, those taking vibegron experienced 0.22 fewer episodes of nocturia (P = .002), 0.8 fewer episodes of urgency incontinence (P = .003), a 0.9-point difference in improvement in the International Prostate Symptom Score (P < .0001), and about 15 mL more volume voided (P < .0001) compared to those receiving placebo, the researchers reported.

“The clinical significance of these findings is that vibegron represents an effective pharmacologic option for managing overactive bladder in the context of concomitant benign prostatic hyperplasia, which is a broader context than its original approval for overactive bladder alone,” Dr. Watts said.

Data from 969 patients on the overactive bladder quality-of-life questionnaire found that the symptom bother score was 6.2 points better for men in the vibegron group than those who took a placebo (P < .0001) at 12 weeks. Similarly, the total health-related quality-of-life score was 4.3 points better in the vibegron group (P < .0001). Measures of concern, coping, and sleep also improved significantly in the men taking vibegron and remained significant at 24 weeks (P < .0001).

Rates of adverse events were similar in the vibegron (45%) and placebo (39%) groups. The most common adverse event was hypertension, which occurred in 9% of the vibegron group and 8.3% of men in the placebo group.

The research was funded by Sumitomo Pharma America, Inc., which makes vibegron. Dr. Staskin is a consultant for Astellas, AzuraBio, Sumitomo Pharma America, Inc., and UroCure; is a lecturer for Astellas and Sumitomo; and holds other interests in UroCure, AzuraBio, and Quillitin Pharma. Three co-authors are Sumitomo employees; one is an investigator for Sumitomo, and another has consulted for Hologic, received research funding from Allergan/AbbVie and Uromedica, and been involved in clinical trials on behalf of Sumitomo. Dr. Watts reported no relevant financial conflicts of interest.

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

The medication vibegron led to improvements in symptoms of overactive bladder and overall quality of life in men undergoing treatment for benign prostatic hyperplasia, according to findings from a phase 3 trial presented at the annual meeting of the American Urological Association (AUA) and data published in the Journal of Urology.

“Vibegron was associated with significant reductions in daily micturition and urgency episodes, as well as our secondary endpoints,” David R. Staskin, MD, an associate professor of urology at Tufts University School of Medicine in Boston, told attendees. “Symptoms really did improve compared to placebo as early as week 2.”

Vibegron is a selective beta-3 adrenergic receptor agonist approved in 2020 by the US Food and Drug Administration for the treatment of overactive bladder.

However, treating overactive bladder symptoms in patients undergoing benign prostatic hyperplasia treatment is more complex because benign prostatic hyperplasia itself can contribute to overactive bladder symptoms, said Kara Watts, MD, an associate professor of urology at Montefiore Einstein in New York City, who was not involved in the new research.

“Management of overactive bladder in this setting may require treatment of benign prostatic hyperplasia as well, but a discussion of the relationship between benign prostatic hyperplasia and overactive bladder symptoms is important,” Dr. Watts told this news organization. “Beyond consideration of treatment for benign prostatic hyperplasia — which can be in the form of medications or surgeries to reduce the size of the prostate — treatment of overactive bladder can include behavioral modification,” such as avoiding bladder irritants, timed voiding, managing constipation, and nighttime liquid restriction,” as well as “medications, percutaneous tibial nerve stimulation, and occasionally more invasive options.”

Vibegron “represents a very attractive and effective pharmaceutical management option for overactive bladder,” both in patients with and without benign prostatic hyperplasia, Dr. Watts said. “It has a favorable side-effect profile compared to other oral agents that can be prescribed for overactive bladder, such as anticholinergics, and also has the added benefit of a much lower risk of urinary retention in comparison to most other oral agents.”

Among 1104 men at least 45 years old who were undergoing treatment for benign prostatic hyperplasia and had symptoms of overactive bladder, 538 received 75 mg of vibegron and 542 received a placebo. The men in the vibegron group showed 2.04 fewer mean daily urinations at 12 weeks and 2.2 fewer at 24 weeks compared to 1.3 fewer at both 12 and 24 weeks for men in the placebo group (P < .0001), according to the researchers.

The drug also reduced urgency of urination. Mean daily episodes of urgency were 2.88 fewer at 12 weeks and 3.07 fewer at 24 weeks in the vibegron group compared to 1.93 and 2.17 fewer, respectively, in the placebo group (P < .0001).

In secondary endpoints, those taking vibegron experienced 0.22 fewer episodes of nocturia (P = .002), 0.8 fewer episodes of urgency incontinence (P = .003), a 0.9-point difference in improvement in the International Prostate Symptom Score (P < .0001), and about 15 mL more volume voided (P < .0001) compared to those receiving placebo, the researchers reported.

“The clinical significance of these findings is that vibegron represents an effective pharmacologic option for managing overactive bladder in the context of concomitant benign prostatic hyperplasia, which is a broader context than its original approval for overactive bladder alone,” Dr. Watts said.

Data from 969 patients on the overactive bladder quality-of-life questionnaire found that the symptom bother score was 6.2 points better for men in the vibegron group than those who took a placebo (P < .0001) at 12 weeks. Similarly, the total health-related quality-of-life score was 4.3 points better in the vibegron group (P < .0001). Measures of concern, coping, and sleep also improved significantly in the men taking vibegron and remained significant at 24 weeks (P < .0001).

Rates of adverse events were similar in the vibegron (45%) and placebo (39%) groups. The most common adverse event was hypertension, which occurred in 9% of the vibegron group and 8.3% of men in the placebo group.

The research was funded by Sumitomo Pharma America, Inc., which makes vibegron. Dr. Staskin is a consultant for Astellas, AzuraBio, Sumitomo Pharma America, Inc., and UroCure; is a lecturer for Astellas and Sumitomo; and holds other interests in UroCure, AzuraBio, and Quillitin Pharma. Three co-authors are Sumitomo employees; one is an investigator for Sumitomo, and another has consulted for Hologic, received research funding from Allergan/AbbVie and Uromedica, and been involved in clinical trials on behalf of Sumitomo. Dr. Watts reported no relevant financial conflicts of interest.

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

The medication vibegron led to improvements in symptoms of overactive bladder and overall quality of life in men undergoing treatment for benign prostatic hyperplasia, according to findings from a phase 3 trial presented at the annual meeting of the American Urological Association (AUA) and data published in the Journal of Urology.

“Vibegron was associated with significant reductions in daily micturition and urgency episodes, as well as our secondary endpoints,” David R. Staskin, MD, an associate professor of urology at Tufts University School of Medicine in Boston, told attendees. “Symptoms really did improve compared to placebo as early as week 2.”

Vibegron is a selective beta-3 adrenergic receptor agonist approved in 2020 by the US Food and Drug Administration for the treatment of overactive bladder.

However, treating overactive bladder symptoms in patients undergoing benign prostatic hyperplasia treatment is more complex because benign prostatic hyperplasia itself can contribute to overactive bladder symptoms, said Kara Watts, MD, an associate professor of urology at Montefiore Einstein in New York City, who was not involved in the new research.

“Management of overactive bladder in this setting may require treatment of benign prostatic hyperplasia as well, but a discussion of the relationship between benign prostatic hyperplasia and overactive bladder symptoms is important,” Dr. Watts told this news organization. “Beyond consideration of treatment for benign prostatic hyperplasia — which can be in the form of medications or surgeries to reduce the size of the prostate — treatment of overactive bladder can include behavioral modification,” such as avoiding bladder irritants, timed voiding, managing constipation, and nighttime liquid restriction,” as well as “medications, percutaneous tibial nerve stimulation, and occasionally more invasive options.”

Vibegron “represents a very attractive and effective pharmaceutical management option for overactive bladder,” both in patients with and without benign prostatic hyperplasia, Dr. Watts said. “It has a favorable side-effect profile compared to other oral agents that can be prescribed for overactive bladder, such as anticholinergics, and also has the added benefit of a much lower risk of urinary retention in comparison to most other oral agents.”

Among 1104 men at least 45 years old who were undergoing treatment for benign prostatic hyperplasia and had symptoms of overactive bladder, 538 received 75 mg of vibegron and 542 received a placebo. The men in the vibegron group showed 2.04 fewer mean daily urinations at 12 weeks and 2.2 fewer at 24 weeks compared to 1.3 fewer at both 12 and 24 weeks for men in the placebo group (P < .0001), according to the researchers.

The drug also reduced urgency of urination. Mean daily episodes of urgency were 2.88 fewer at 12 weeks and 3.07 fewer at 24 weeks in the vibegron group compared to 1.93 and 2.17 fewer, respectively, in the placebo group (P < .0001).

In secondary endpoints, those taking vibegron experienced 0.22 fewer episodes of nocturia (P = .002), 0.8 fewer episodes of urgency incontinence (P = .003), a 0.9-point difference in improvement in the International Prostate Symptom Score (P < .0001), and about 15 mL more volume voided (P < .0001) compared to those receiving placebo, the researchers reported.

“The clinical significance of these findings is that vibegron represents an effective pharmacologic option for managing overactive bladder in the context of concomitant benign prostatic hyperplasia, which is a broader context than its original approval for overactive bladder alone,” Dr. Watts said.

Data from 969 patients on the overactive bladder quality-of-life questionnaire found that the symptom bother score was 6.2 points better for men in the vibegron group than those who took a placebo (P < .0001) at 12 weeks. Similarly, the total health-related quality-of-life score was 4.3 points better in the vibegron group (P < .0001). Measures of concern, coping, and sleep also improved significantly in the men taking vibegron and remained significant at 24 weeks (P < .0001).

Rates of adverse events were similar in the vibegron (45%) and placebo (39%) groups. The most common adverse event was hypertension, which occurred in 9% of the vibegron group and 8.3% of men in the placebo group.

The research was funded by Sumitomo Pharma America, Inc., which makes vibegron. Dr. Staskin is a consultant for Astellas, AzuraBio, Sumitomo Pharma America, Inc., and UroCure; is a lecturer for Astellas and Sumitomo; and holds other interests in UroCure, AzuraBio, and Quillitin Pharma. Three co-authors are Sumitomo employees; one is an investigator for Sumitomo, and another has consulted for Hologic, received research funding from Allergan/AbbVie and Uromedica, and been involved in clinical trials on behalf of Sumitomo. Dr. Watts reported no relevant financial conflicts of interest.

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

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

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

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

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

In the first randomized controlled trial of prednisone for postvasectomy reversals, fertility researchers found that a high dose of the steroid reduced the rate of subsequent pregnancy.

“This is the first time it’s been shown that high doses [of prednisone] can make someone infertile,” said Landon Trost, MD, director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, and a faculty member at Mayo Clinic, in Rochester, Minnesota, who presented the study (Abstract MP42-19) on May 4 at the 2024 annual meeting of the American Urological Association (AUA) in San Antonio, Texas. 

Dr. Trost called the findings “a real shock. I almost didn’t believe the data when I saw it. It opens up a whole new set of areas for research and exploration.”

Dr. Trost’s clinic performs 1200 reversals per year out of the estimated 20,000 performed annually in the United States, he said. He said his practice has stopped using high-dose prednisone as a result of the study, which he performed at his own expense to examine the varying protocols for vasectomy reversal.

William Berg, MD, director of the Stony Brook Urology Men’s Health Program, in Stony Brook, New York, said that the expected patency rate for modern postvasectomy reversals, if performed properly, can be as high as 98%. However, in some men, patency occurs initially, but the accumulation of scar tissue at the site of reversal causes sperm counts in ejaculate to drop to zero.

Since the 1970s, urologists — with limited research to back — the practice  prescribed prednisone to patients with the goal of preventing scarring and blockages associated with vasectomy reversals. Dr. Berg called this practice “unsubstantiated” and noted that Dr. Trost’s study is the first prospective randomized controlled trial of this approach.

The study enrolled 75 men, with a mean age of roughly 38 years. The mean time since vasectomy was 6.6 years.

The low-dose arm (25 patients) received 5 mg of prednisone per week alternating with no treatment per week over 6 months. The high-dose arm (n = 14) received 20 mg of prednisone, tapered to 10 mg, 5 mg, and then off over 1 month, followed by every other month for 6 months. A prednisone-as-needed group (n = 11) received a tapered course of prednisone on the basis of whether they had decreasing or zero sperm counts. They received 20 mg for 5 days, 10 mg for 5 days, and 5 mg for 20 days.

A control arm (n = 25) received no prednisone.

Urologists typically use patency rates to measure success of vasectomy reversals. The patency rates at 12 months in Dr. Trost’s study were 100% in the control participants, prednisone-as-needed, and low-dose groups and 92% (13/14) in the high-dose group. 

Dr. Trost said that the story was told in the pregnancy rates. At the 1-year mark, pregnancy rates were 67% in the low-risk group and 65% in the control group but 38% and 17% in the prednisone-as-needed and high-dose group, respectively (P = .02).

The mean maximum sperm concentration was 40 million per mL, ranging from 29.7 million per mL for men in the control group to 54.3 million per mL in the low-dose group.

Dr. Trost said that he immediately stopped using high doses of prednisone in his practice and predicted that other clinics would follow suit. 

Dr. Berg said the drop in pregnancies with higher doses of prednisone is a first-time finding and suggests that a high dose may “be detrimental to sperm function in some way. I don’t think this ever has been described before.”

Dr. Trost financed the study himself. Dr. Berg reported no conflicts.

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

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .

Up to 60% of men with erectile dysfunction who were not candidates for phosphodiesterase 5 (PDE5) inhibitors achieved erections in less than 10 minutes after a single application of a first-on-the-market nonprescription gel to the glans, a new study found. 

Wayne Hellstrom, MD, chief of andrology at Tulane School of Medicine in New Orleans, who presented the study of MED3000 [Eroxon] on May 5 at the 2024 annual meeting of the American Urological Association in San Antonio, Texas, said that the gel is considered to be a device by the US Food and Drug Administration (FDA). The agency approved the product in June 2023.

A spokesman for Futura, which makes MED3000, said that the gel will be on the market 2025. No price for the United States has been announced, but a four-pack of single-use tubes sells for the equivalent of roughly $31 in the United Kingdom.

Dr. Hellstrom, a former adviser to Futura, he said he expects MED3000 will be “a potential first-line therapy in addition to PDE5 inhibitors,” which are vasodilating drugs that stimulate the corpora cavernosa of the penis, facilitating erection with sexual stimulation.

He noted that PDE5s are contraindicated for many men; are not tolerated in others; are not completely effective; or work too slowly, taking 1-2 hours to work. As a result, up to 50% of patients cease using a PDE5 inhibitor within 1 year, he said. 

Futura said the gel contains a combination of volatile solvents which, when applied to the head of the penis, evaporate rapidly, stimulating nerve endings through an initial cooling effect followed by a warming sensation. This reaction releases nitric oxide, relaxing the smooth muscle tissue inside the penis and increasing blood flow that is needed to obtain an erection.

Dr. Hellstrom noted that MED3000 is noninvasive and causes no side effects and is slightly more effective if applied by a partner.

The new findings come from two studies of 250 men with erectile dysfunction (FM57) who used MED3000 over 12 weeks and a randomly assigned arm (FM71) with two groups of 48 men who used either MED3000 or 5 mg of tadalafil over 24 weeks.

Erections were achieved in less than 10 minutes in 60.1% of men in the FM57 group and 44.9% of those in the FM71 group.

Overall, less than 2% of the men who usedMED3000 and 4% of those who took tadalafil reported adverse effects. These events included headaches in 3% of the combined MED3000 group and 19.1% of the tadalafil group. Roughly 1% of men who used MED3000 reported penile burning sensation compared with none in the group taking tadalafil.
 

Problematic Design? 

Kevin McVary, MD, a professor of urology at Stritch School of Medicine of Loyola University, outside of Chicago, and director of the Center for Male Health, criticized the study design and added that he did not believe MED3000 had been proven beneficial.

“Are they expecting the Cialis 5 mg to work within 10 minutes? Because it doesn’t,” Dr. McVary said. “It doesn’t get absorbed into the bloodstream for about 2.5 hours.”

Dr. McVary said that men with erectile dysfunction will probably do anything to avoid seeing a physician about the condition, which could make MED3000 highly marketable.

However, he said, examinations would be important to detect unrecognized underlying cardiac disease, especially in younger men. “ED can function as the classic canary in a coal mine where it tells you who’s at risk for unexpected early death,” he said.

Dr. Hellstrom is a former adviser to Futura Medical Developments, which funded the research. Dr. McVary reported no relevant financial conflicts of interest.  
 

A version of this article appeared on Medscape.com .