Men's Health

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

When Sigmund Freud claimed that “anatomy is destiny” he was referring to anatomical sex as a determinant of personality traits. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,”

That notion has been widely discredited, but Freud appears to be inadvertently right in one respect: When it comes to chronic obstructive pulmonary disease (COPD), anatomy really is destiny, and sex may be as well, pulmonary researchers say.

There is a growing body of evidence to indicate that COPD affects men and women differently, and that men and women patients with COPD require different clinical management. Yet women are often underdiagnosed or misdiagnosed, partly because of poorly understood sex differences, but also because of cultural biases.

But plunging any farther into the weeds, it’s important to define terms. Although various investigators have used the terms “sex” and “gender” interchangeably, sex is the preferred term when referring to biological attributes of individual patients, while gender refers to personal identity.

These distinctions are important, contended Amik Sodhi, MBBS, MPH, from the division of allergy, pulmonology, and critical care medicine at the University of Wisconsin–Madison.

“Sex is essentially a biologic construct, so it’s got to do with the sex chromosomes, the genetics of that person, and it refers to the anatomic variations that can change susceptibility to different diseases,” she said in an interview.

An example of sex differences or “sexual dimorphism” can be found in a recent meta-analysis of sex-based genetic associations by Megan Hardin, MD, MPH from Brigham & Women’s Hospital in Boston and colleagues.

They reported that CELSR1, a gene involved in fetal lung development, was expressed more among women than among men and that a single nucleotide polymorphism in the gene was associated with COPD among women smokers, but not among men smokers.

The finding points to a potential risk locus for COPD in women, and could help shed light on sexual dimorphism in COPD, Dr. Hardin and colleagues said.

In contrast to sex, “gender is more of a psychosocial construct which can impact how diseases manifest themselves, how they are potentially managed, and what outcomes might occur for that particular disease,” Dr. Sodhi said.

She and her colleagues recently published a review of sex and gender in common lung disorders and sleep in the journal CHEST, where they wrote that the “influence of sex and gender is portrayed in epidemiological data, disease pathogenesis and pathophysiology, clinical manifestations, response to treatment, access to care, and health outcomes. Hence, sex and gender should be considered in all types of research, clinical practice and educational curricula.”

For example, as previously reported at the 2021 annual meeting of the American Thoracic Society, sex-specific differences in the severity of symptoms and prevalence of comorbidities in patients with COPD may point to different criteria for diagnosing cardiac comorbidities in women and men.

Those conclusions came from a retrospective analysis of data on 795 women and 1,251 men with GOLD (Global Initiative for Chronic Obstructive Lung Disease) class 1-3 disease.

The investigators looked at the patients’ clinical history, comorbidities, lung function, COPD Assessment Test scores, and modified Medical Research Council (mMRC) dyspnea score, and found significant differences between men and women for most functional parameters and comorbidities, and for CAT items of cough, phlegm, and energy.

In logistic regression analysis, predictors for cardiac disease in men were energy, mMRC score, smoking status, body mass index, age, and spirometric lung function, but in women only age was significantly predictive for cardiac disease.

An example of gender effects on COPD differences in men and women is the increase in cigarette advertising aimed at women in the 1960s and the advent of women-targeted brands such as Virginia Slims, which in turn lead to increased smoking rates among women. In addition, in the developing world, where the sex/gender gap in COPD is narrowing, women tend to have greater exposure to wood smoke and cooking fuels in unventilated or poorly ventilated spaces, compared with men.
 

Increasing incidence among women

According to the Centers for Disease Control and Prevention, chronic lower respiratory diseases, primarily COPD, were the fourth-leading cause of death in women in the United States in 2018, following only heart disease, cancer, and accidents/injuries.

And as a CDC analysis of data from the 2013 Behavioral Risk Factor Surveillance System showed, women were more likely to report being told by a physician that they had COPD than did men (6.6%, compared with 5.4%).

Dr. Sodhi and colleagues noted that, at all time points examined from 2005 to 2014, women had a higher proportion than men of COPD hospitalizations and in-hospital deaths. They also noted that female sex is associated with a threefold risk for severe early-onset COPD, and that women with COPD have lower diffusion capacity of lungs for carbon monoxide, despite having higher predicted forced expiratory volume in 1 second, compared with men.

“Historically, COPD wasn’t a disease that was so prevalent in women. It’s been in the past 20 years that the trends have changed,” said Patricia Silveyra, MSc, PhD, ATSF, associate professor of environmental and occupational health at Indiana University, Bloomington.

The increasing prevalence of COPD among women cannot be explained by smoking alone, she said in an interview.

“It used to be thought that it was because more women smoked, but actually a lot of women who don’t smoke can develop COPD, so it appears to be probably something environmental, but because it used to be a disease of older men, in the clinic there was also a bias to diagnose men with COPD, and women with asthma, so a lot of women went underdiagnosed,” Dr. Silveyra said.

In their review, Dr. Sodhi and colleagues noted that women with COPD “may be underdiagnosed as a result of having different symptoms from those classically recognized. Reasons for underdiagnosis or a delay in diagnosis may also be due to lack of a formal evaluation with spirometry, women seeking care later in the course of disease, physician bias, or associated fatigue or depression misdirecting diagnostic strategies. Underdiagnosis may be associated with psychological distress and worse health-related quality of life.”

Although the evidence is mixed, women tend to present more frequently with the chronic bronchitis phenotype of COPD, compared with the emphysema phenotype, and women tend to have greater degrees of pulmonary function impairment when exposed to tobacco smoke, even after controlling for differences in height and weight.

“For the same amount of exposure to tobacco smoke, females are likely to develop more severe airflow limitation at an earlier age than males, and have more exacerbation,” Dr. Sodhi and colleagues wrote.

Both Dr. Silveyra and Dr. Sodhi said that reason why men and women differ in their physiological reactions to smoke are still unknown.
 

Sex differences in drug responses

There is only limited evidence to indicate that women and men respond differently to various therapeutic agents, but what is clear is that more research into this area is needed, Dr. Sodhi and Dr. Silveyra said.

For example, among the few studies that have documented sex differences, one showed no sex differences in the efficacy of salmeterol/fluticasone combination therapy for reducing exacerbations or improving quality of life, whereas another showed that women were more likely than men to experience COPD symptoms or exacerbations after stopping inhaled corticosteroids, Dr. Sodhi and colleagues noted.

Both Dr. Sodhi and Dr. Silveyra emphasized the need for clinical trials that study the effects of sex on treatment outcomes in COPD, which could lead to better, more personalized therapeutic regimens that take sex and gender into account.

Dr. Sodhi and colleagues offered the following advice to clinicians: “Interaction with female patients should take into account that their symptoms may not conform to traditionally accepted presentations. Challenges exist for female patients at all levels of health care interaction and as clinicians we need to acknowledge the bias and willfully work toward recognition and elimination of unconscious and conscious bias. Empowering our patients to have frank discussions with their health care team when they perceive bias is another step to help promote equity.”

The review by Dr. Sodhi and colleagues was supported by grants from the National Institutes of Health. Dr. Sodhi and Dr. Silveyra reported having no conflicts of interest to disclose.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.

A study of testicular cancer mortality finds worse outcomes among Hispanic men, but better outcomes among Black men.

The findings were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

Incidence rates for testicular cancer in the United States have increased slowly in recent decades, said Anushka Ghosh, a clinical research coordinatory with Massachusetts General Hospital, Boston. Her analysis found mortality increases from 1999 to 2019 to be significantly greater among Hispanic men. The increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

Among Black men, testicular cancer–specific mortality rates declined by 0.0007 per 100,000, compared with a marginally significant increase of 0.0006 per 100,000 among White men (P =.049).

“Given that testicular cancer generally has a favorable prognosis, it is concerning that the mortality rate for this disease is increasing,” said Sophia C. Kamran, MD, the study’s lead author and a radiation oncologist at Massachusetts General Hospital.

Dr. Kamran urged new efforts to understand these trends and to make testicular cancer care more accessible for all patients.

Ms. Ghosh said that other researchers have identified the same disparity among Hispanic men with prostate cancer. “Even though testicular cancer is a rare, our finding warrants further investigation to find the basis of these disparities to better serve the Hispanic community.”

Other studies have shown higher likelihood of later stage diagnosis and worse survival outcomes among Black patients.

No funding sources were reported for this study.

The first condom specifically designed for use during anal sex has gained Food and Drug Administration approval.

Anal intercourse is considered to be much riskier than vaginal sex for the transmission of infections such as HIV and HPV, a risk factor for anal cancer, agency officials said in a statement Feb. 23 announcing the decision. And though the Centers for Disease Control and Prevention has long encouraged the use of a condom during anal intercourse, the FDA had not until now deemed this practice safe.

The latex ONE Male Condom, from prophylactic maker Global Protection Corp. of Boston, has already been available for vaginal sex. The FDA action now allows the company to market the product for anal intercourse.

“This authorization helps us accomplish our priority to advance health equity through the development of safe and effective products that meet the needs of diverse populations,” Courtney Lias, PhD, the director of the FDA’s Office of GastroRenal, ObGyn, General Hospital, and Urology Devices, said in a statement.

The FDA said it relied on an Emory University clinical study of condom safety of more than 500 men. Those who took part in the study were evenly divided between men who have sex with men and men who have sex with women. The condom failure rate, meaning that a condom either broke or slipped, was less than 1% during anal sex. The failure rate was 3 times higher during vaginal intercourse.

The Emory researchers also found that roughly 70% of men who have sex with men would be more likely to use condoms marked as safe for anal sex, according to a survey of 10,000 people.

ONE Male Condoms sell for between $3.48 for a three-pack and $14.48 for a 24-pack, according to Milla Impola, Global Protection’s director of marketing and communications. The FDA said the condom should be used with a condom-compatible lubricant when used during anal sex.

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

The first condom specifically designed for use during anal sex has gained Food and Drug Administration approval.

Anal intercourse is considered to be much riskier than vaginal sex for the transmission of infections such as HIV and HPV, a risk factor for anal cancer, agency officials said in a statement Feb. 23 announcing the decision. And though the Centers for Disease Control and Prevention has long encouraged the use of a condom during anal intercourse, the FDA had not until now deemed this practice safe.

The latex ONE Male Condom, from prophylactic maker Global Protection Corp. of Boston, has already been available for vaginal sex. The FDA action now allows the company to market the product for anal intercourse.

“This authorization helps us accomplish our priority to advance health equity through the development of safe and effective products that meet the needs of diverse populations,” Courtney Lias, PhD, the director of the FDA’s Office of GastroRenal, ObGyn, General Hospital, and Urology Devices, said in a statement.

The FDA said it relied on an Emory University clinical study of condom safety of more than 500 men. Those who took part in the study were evenly divided between men who have sex with men and men who have sex with women. The condom failure rate, meaning that a condom either broke or slipped, was less than 1% during anal sex. The failure rate was 3 times higher during vaginal intercourse.

The Emory researchers also found that roughly 70% of men who have sex with men would be more likely to use condoms marked as safe for anal sex, according to a survey of 10,000 people.

ONE Male Condoms sell for between $3.48 for a three-pack and $14.48 for a 24-pack, according to Milla Impola, Global Protection’s director of marketing and communications. The FDA said the condom should be used with a condom-compatible lubricant when used during anal sex.

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

The first condom specifically designed for use during anal sex has gained Food and Drug Administration approval.

Anal intercourse is considered to be much riskier than vaginal sex for the transmission of infections such as HIV and HPV, a risk factor for anal cancer, agency officials said in a statement Feb. 23 announcing the decision. And though the Centers for Disease Control and Prevention has long encouraged the use of a condom during anal intercourse, the FDA had not until now deemed this practice safe.

The latex ONE Male Condom, from prophylactic maker Global Protection Corp. of Boston, has already been available for vaginal sex. The FDA action now allows the company to market the product for anal intercourse.

“This authorization helps us accomplish our priority to advance health equity through the development of safe and effective products that meet the needs of diverse populations,” Courtney Lias, PhD, the director of the FDA’s Office of GastroRenal, ObGyn, General Hospital, and Urology Devices, said in a statement.

The FDA said it relied on an Emory University clinical study of condom safety of more than 500 men. Those who took part in the study were evenly divided between men who have sex with men and men who have sex with women. The condom failure rate, meaning that a condom either broke or slipped, was less than 1% during anal sex. The failure rate was 3 times higher during vaginal intercourse.

The Emory researchers also found that roughly 70% of men who have sex with men would be more likely to use condoms marked as safe for anal sex, according to a survey of 10,000 people.

ONE Male Condoms sell for between $3.48 for a three-pack and $14.48 for a 24-pack, according to Milla Impola, Global Protection’s director of marketing and communications. The FDA said the condom should be used with a condom-compatible lubricant when used during anal sex.

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

Introduction

Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.¹

Infertility following vaccination

The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.² According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”³

Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.⁴

Expanding on the theme of fertility during the pandemic, a number of false claims^5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.⁵ Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.⁵

The vaccine is the best option

While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.⁶

In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.^8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.⁸ In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.

A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.¹⁰ If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).¹¹

Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.

References

1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.

2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.

3. Broderick JM. Urology Times. 2021 June.

4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.

5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.

6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.

7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.

8. Tesarik J. J Fertil Preserv. 2021;2:art246111.

9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.

10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.

11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.

Introduction

Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.¹

Infertility following vaccination

The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.² According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”³

Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.⁴

Expanding on the theme of fertility during the pandemic, a number of false claims^5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.⁵ Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.⁵

The vaccine is the best option

While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.⁶

In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.^8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.⁸ In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.

A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.¹⁰ If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).¹¹

Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.

References

1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.

2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.

3. Broderick JM. Urology Times. 2021 June.

4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.

5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.

6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.

7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.

8. Tesarik J. J Fertil Preserv. 2021;2:art246111.

9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.

10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.

11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.

Introduction

Amidst an aggressive vaccination campaign for COVID-19, misinformation has spread over the Internet, affecting public perception and making some people hesitant to participate in ongoing immunization campaigns. Of chief concern are issues pertaining to fertility or viability of sperm – information circulating on social networks posits that the coronavirus vaccine may influence infertility in men, which, according to physicians, is not grounded in reality. From the perspective of evidence-based medicine, there is a dearth of information suggesting an untoward effect of the vaccine on male fertility. The risk of adverse reactions arising from approved vaccines is negligible, with mild, albeit controllable, side effects demonstrated by patients in clinical trials. Therefore, there is no plausible reason for the general public to avoid vaccinations.¹

Infertility following vaccination

The source of confusion can be traced back to a study conducted by researchers at the University of Miami Miller School of Medicine; the general public has conflated a side effect of the virus, namely, infertility and erectile dysfunction, with that of the vaccine.² According to Ranjith Ramasamy, MD, director of the urology program at Miller, “We were the first to demonstrate that the COVID virus, itself, can affect male fertility and be a potential cause for erectile dysfunction. We are now the first to examine if there is any impact of the COVID vaccine on male fertility potential, which we did not find.”³

Coronavirus can indeed cause significant damage to the testicular tissue of infected men by means of mediating ACE2 expression on Leydig and Sertoli cells of the testis. It should be noted that COVID-19 may potentially attack any type of cell in the body that expresses the enzyme ACE2. However, it is particularly harmful to cells with high levels of expression of this enzyme, such as testicular cells. The spermatogenesis process can be affected, thereby posing a risk to male fertility.⁴

Expanding on the theme of fertility during the pandemic, a number of false claims^5-7 about the vaccine and its overall effect on the placenta and fertility have also emerged as a contentious topic for debate on social media; doctors continue to explain why the theories are not reasonable or a cause for concern. The World Health Organization (WHO) provides recommendations on COVID-19 vaccinations for pregnant and/or lactating women and encourages a shared decision process involving risk/benefit assessment with the prescribing physician.⁵ Pregnant women, especially those with underlying comorbid conditions, are susceptible to developing severe symptom manifestations of COVID-19 with the disease also being associated with an increased likelihood of premature birth. As far as lactating women are concerned, the evidence thus far has indicated that the risk of side effects of the vaccine is very low, suggesting that these women could be vaccinated.⁵

The vaccine is the best option

While more studies are needed to ascertain the relationship between COVID-19 and male infertility, the vaccine is currently the best option for those who are concerned about their fertility from exposure to the coronavirus. Because of delayed wholesale acceptance of vaccines by the general population, clinicians should continue to emphasize the importance of preventive care with respect to disease exposure.⁶

In addition, those who are concerned with fertility can opt for ways to preserve their reproductive capacity, such as the removal of semen for freezing sperm, albeit with adherence to sperm-washing procedures to preclude cross-contamination from viruses.^8,9 For the preservation of sperm, the noninvasive method is often performed, preferably collected in several samples. Then, the semen is cryopreserved.⁸ In some instances, the sperm can also be removed directly from the testicles with a simple needle or by means of a minor surgical procedure.

A wait and try approach is advocated by clinicians for individuals who have already experienced COVID-19 symptoms and are therefore concerned about the prospect of childbearing.¹⁰ If the couple is unable to conceive after a year of trying, it is recommended that they consult a reproductive specialist; the clinician can carry out a comprehensive evaluation and order a series of tests to identify the source of the problem, indicating whether there are alternative methods for helping the couple to start a family (addressing the underlying factors involved in infertility, or treating via assisted reproduction procedures, such as in vitro fertilization).¹¹

Dr. Aman is faculty member at the biology department of City Colleges of Chicago, and a postdoctoral researcher at the International Maternal and Child Health Foundation (IMCHF). She disclosed no relevant financial relationships. Dr. Islam is a medical writer for the IMCHF, Montreal, is based in New York, and disclosed no relevant financial relationships. Mr. Choudhry is a research assistant at the IMCHF and he has no disclosures. Dr. Zia Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the IMCHF. He has no disclosures.

References

1. Berry SD et al. J Am Geriatr Soc. 2021 May;69(5):1140-6.

2. Achua JK et al. World J Men’s Health. 2021 Jan;39(1):65-74.

3. Broderick JM. Urology Times. 2021 June.

4. Huang C et al. Andrology. 2021 Jan;9(1):80-7.

5. Sajjadi NB et al. J Osteopath Med. 2021 Apr 12;121(6):583-7.

6. Sallam M et al. Vaccines. 2021 Jan;9(1):42.

7. Islam MS et al. PloS One. 2021 May 12;16(5):e0251605.

8. Tesarik J. J Fertil Preserv. 2021;2:art246111.

9. Adiga SK et al. Reprod BioMed Online. 2020 Dec;41(6):991-7.

10. FAQs related to COVID-19. Q: If I get sick or test positive for COVID-19, when is it safe to become pregnant? American Society for Reproductive Medicine.

11. Cross C. Wellness and Prevention: Why can’t I get pregnant? John Hopkins Medicine.

NEW YORK (Reuters) – After doctors removed the wrong testis from a young man, the search was on for a surgeon who might be willing to try to replant it.

A new case report details the experience of a 25-year-old patient who had developed testicular pain and a palpable mass in his right testis; he went to a local hospital for a radical orchiectomy only to have the surgical team remove the left – wrong – testis.

Once the team recognized their error, they began searching for a center with microsurgical capacity to replant the testis. The surgery to replant the organ is described in an article published in Urology.

“The take-home message is that microsurgery can be used to reattach an organ, in the case of a wrong-site surgery,” lead author Dr. Fatma Tuncer, a microsurgery fellow at the Cleveland Clinic, in Ohio, at the time of the surgery, told Reuters Health by email. She is now an assistant professor of plastic surgery at the University of Utah.

“The vast majority of surgeries, including urologic procedures will never have such an event, but there are helpful groups of physicians that are available to reduce the morbidity of such an event,” said coauthor Dr. Brian Gastman, a professor of surgery at the Case Western School of Medicine and a surgeon at the Cleveland Clinic.

“We were, I believe, the third one contacted, each one causing a greater time of ischemia,” Dr. Gastman told Reuters Health by email. “I accepted the patient and in doing so had the buy-in of my urology and anesthesia colleagues.”

Once Dr. Gastman and his team agreed to take on the task, the patient, and his testis, were flown to Cleveland. Once the patient arrived, he was counseled on the risks and benefits of the surgery. After agreeing to the surgery, the patient was taken to the OR immediately by the plastic surgery and urology teams.

Prior to initiating anesthesia, the testicle was examined and the urology team performed testicular sperm extraction as the patient did not have any biological children. The sperm were transported to a CLIA-certified andrology lab and were cryopreserved.

Next, the team examined the testis and spermatic cord under the microscope. The team identified the testicular artery, veins and vas deferens and marked them with prolene sutures. They next placed the testis in a moist gauze over ice until the recipient vessels were prepared.

After the team reconnected vessels, they observed strong arterial and venous Doppler flow on both testicular vessels and the testis itself. Five days after the replantation surgery, the team performed a radical orchiectomy on the correct side.

Dr. Gastman isn’t sure how well the testis will perform over time. “I cannot speak too much on this as it is ongoing,” he said. “But he will likely need some level of hormonal supplementation. I can state that the testis is alive and palpable.”

This is a “very interesting paper,” said Dr. Miroslav Djordjevic, a professor of urology at the Icahn School of Medicine at Mount Sinai, New York. “Congratulations to colleagues for a great idea for solving this wrong-site surgery with very precise microsurgical technique and new insight in the fight to save the organs.”

Still, Dr. Djordjevic told Reuters Health by email, “postoperatively, the authors confirmed there was not complete testicular function based on testosterone levels and hypotrophy of the reimplanted testis. The main reason is the time between removal and reimplanation. Based on experiences with testicular torsion, four to six hours is the maximum that will offer restoration of volume and function. Here, a longer period (10 hours) resulted in poor outcomes.”

“Our experience with testicular implantation in monozygotic twins showed great success (Belgrade University, Serbia, December 2019, personal report) because the cold ischemia was only one hour,” Dr. Djordjevic said.
 

Reuters Health Information © 2022

NEW YORK (Reuters) – After doctors removed the wrong testis from a young man, the search was on for a surgeon who might be willing to try to replant it.

A new case report details the experience of a 25-year-old patient who had developed testicular pain and a palpable mass in his right testis; he went to a local hospital for a radical orchiectomy only to have the surgical team remove the left – wrong – testis.

Once the team recognized their error, they began searching for a center with microsurgical capacity to replant the testis. The surgery to replant the organ is described in an article published in Urology.

“The take-home message is that microsurgery can be used to reattach an organ, in the case of a wrong-site surgery,” lead author Dr. Fatma Tuncer, a microsurgery fellow at the Cleveland Clinic, in Ohio, at the time of the surgery, told Reuters Health by email. She is now an assistant professor of plastic surgery at the University of Utah.

“The vast majority of surgeries, including urologic procedures will never have such an event, but there are helpful groups of physicians that are available to reduce the morbidity of such an event,” said coauthor Dr. Brian Gastman, a professor of surgery at the Case Western School of Medicine and a surgeon at the Cleveland Clinic.

“We were, I believe, the third one contacted, each one causing a greater time of ischemia,” Dr. Gastman told Reuters Health by email. “I accepted the patient and in doing so had the buy-in of my urology and anesthesia colleagues.”

Once Dr. Gastman and his team agreed to take on the task, the patient, and his testis, were flown to Cleveland. Once the patient arrived, he was counseled on the risks and benefits of the surgery. After agreeing to the surgery, the patient was taken to the OR immediately by the plastic surgery and urology teams.

Prior to initiating anesthesia, the testicle was examined and the urology team performed testicular sperm extraction as the patient did not have any biological children. The sperm were transported to a CLIA-certified andrology lab and were cryopreserved.

Next, the team examined the testis and spermatic cord under the microscope. The team identified the testicular artery, veins and vas deferens and marked them with prolene sutures. They next placed the testis in a moist gauze over ice until the recipient vessels were prepared.

After the team reconnected vessels, they observed strong arterial and venous Doppler flow on both testicular vessels and the testis itself. Five days after the replantation surgery, the team performed a radical orchiectomy on the correct side.

Dr. Gastman isn’t sure how well the testis will perform over time. “I cannot speak too much on this as it is ongoing,” he said. “But he will likely need some level of hormonal supplementation. I can state that the testis is alive and palpable.”

This is a “very interesting paper,” said Dr. Miroslav Djordjevic, a professor of urology at the Icahn School of Medicine at Mount Sinai, New York. “Congratulations to colleagues for a great idea for solving this wrong-site surgery with very precise microsurgical technique and new insight in the fight to save the organs.”

Still, Dr. Djordjevic told Reuters Health by email, “postoperatively, the authors confirmed there was not complete testicular function based on testosterone levels and hypotrophy of the reimplanted testis. The main reason is the time between removal and reimplanation. Based on experiences with testicular torsion, four to six hours is the maximum that will offer restoration of volume and function. Here, a longer period (10 hours) resulted in poor outcomes.”

“Our experience with testicular implantation in monozygotic twins showed great success (Belgrade University, Serbia, December 2019, personal report) because the cold ischemia was only one hour,” Dr. Djordjevic said.
 

Reuters Health Information © 2022

NEW YORK (Reuters) – After doctors removed the wrong testis from a young man, the search was on for a surgeon who might be willing to try to replant it.

A new case report details the experience of a 25-year-old patient who had developed testicular pain and a palpable mass in his right testis; he went to a local hospital for a radical orchiectomy only to have the surgical team remove the left – wrong – testis.

Once the team recognized their error, they began searching for a center with microsurgical capacity to replant the testis. The surgery to replant the organ is described in an article published in Urology.

“The take-home message is that microsurgery can be used to reattach an organ, in the case of a wrong-site surgery,” lead author Dr. Fatma Tuncer, a microsurgery fellow at the Cleveland Clinic, in Ohio, at the time of the surgery, told Reuters Health by email. She is now an assistant professor of plastic surgery at the University of Utah.

“The vast majority of surgeries, including urologic procedures will never have such an event, but there are helpful groups of physicians that are available to reduce the morbidity of such an event,” said coauthor Dr. Brian Gastman, a professor of surgery at the Case Western School of Medicine and a surgeon at the Cleveland Clinic.

“We were, I believe, the third one contacted, each one causing a greater time of ischemia,” Dr. Gastman told Reuters Health by email. “I accepted the patient and in doing so had the buy-in of my urology and anesthesia colleagues.”

Once Dr. Gastman and his team agreed to take on the task, the patient, and his testis, were flown to Cleveland. Once the patient arrived, he was counseled on the risks and benefits of the surgery. After agreeing to the surgery, the patient was taken to the OR immediately by the plastic surgery and urology teams.

Prior to initiating anesthesia, the testicle was examined and the urology team performed testicular sperm extraction as the patient did not have any biological children. The sperm were transported to a CLIA-certified andrology lab and were cryopreserved.

Next, the team examined the testis and spermatic cord under the microscope. The team identified the testicular artery, veins and vas deferens and marked them with prolene sutures. They next placed the testis in a moist gauze over ice until the recipient vessels were prepared.

After the team reconnected vessels, they observed strong arterial and venous Doppler flow on both testicular vessels and the testis itself. Five days after the replantation surgery, the team performed a radical orchiectomy on the correct side.

Dr. Gastman isn’t sure how well the testis will perform over time. “I cannot speak too much on this as it is ongoing,” he said. “But he will likely need some level of hormonal supplementation. I can state that the testis is alive and palpable.”

This is a “very interesting paper,” said Dr. Miroslav Djordjevic, a professor of urology at the Icahn School of Medicine at Mount Sinai, New York. “Congratulations to colleagues for a great idea for solving this wrong-site surgery with very precise microsurgical technique and new insight in the fight to save the organs.”

Still, Dr. Djordjevic told Reuters Health by email, “postoperatively, the authors confirmed there was not complete testicular function based on testosterone levels and hypotrophy of the reimplanted testis. The main reason is the time between removal and reimplanation. Based on experiences with testicular torsion, four to six hours is the maximum that will offer restoration of volume and function. Here, a longer period (10 hours) resulted in poor outcomes.”

“Our experience with testicular implantation in monozygotic twins showed great success (Belgrade University, Serbia, December 2019, personal report) because the cold ischemia was only one hour,” Dr. Djordjevic said.
 

Reuters Health Information © 2022

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

A small study of deceased nonvaccinated men who died of COVID-19 complications suggests the testes may be a sanctuary for the SARS-CoV-2 virus, raising questions about potential consequences for reproductive health among those infected.

The study, published online Feb. 8 on the preprint server MedRxiv, found that “patients who become critically ill exhibit severe damages and may harbor the active virus in testes,” which can “serve as a viral sanctuary.”

Guilherme M.J. Costa, PhD, a professor at Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, led the study, which has not yet been peer-reviewed.

“A critical point of this article is that the virus was active in the patient’s testis after a long period of infection, indicating that the testis is able to maintain the viable virus for extended periods. It happens for many kinds of viruses in this genital organ,” Dr. Costa said in an interview.

Brian Keith McNeil, MD, vice-chair, department of urology at SUNY Downstate Health Sciences University in New York, told this news organization that the topic of COVID-19 and fertility has been discussed but data are sparse on the subject.

“The question this raises is whether or not COVID can live in the testes, and based on this it seems it can,” he said, adding that it also raises the question of whether COVID-19 could be transmitted through semen. “It leads one to wonder whether this could have a long-term impact on fertility in men and women.”

The authors wrote that deep testicular evaluation of patients who have been infected with COVID-19 is critical because the testes have one of the highest expressions of angiotensin converting enzyme 2 (ACE2) receptors, which play a large role in entrance of the virus into cells.

“A direct influence of SARS-CoV-2 in testicular cells might deregulate ACE2, elevating the levels of angiotensin II, a potent pro-inflammatory and angiogenic peptide,” the authors wrote.
 

Sperm-producing cells infected

In 2021, the researchers enrolled 11 male patients deceased from COVID-19 complications; none had received a vaccine. Infection was confirmed by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) performed during their hospital stay. All 11 patients were admitted to the intensive care unit with severe pulmonary symptoms.

All but one of the patients had children and none had scrotal symptoms or complaints during their time in the hospital. Their clinical histories revealed no testicular disorders.

Dr. Costa said they found that detecting SARS-CoV-2 mRNA in testes is difficult in a conventional RT-PCR test.

Therefore, “We modified the protocol of the RT-PCR and used nanosensors. We observed that SARS-CoV-2 has a huge tropism for the testes in this context,” he said.

He said the team performed stainings and “discovered that macrophages and germ cells are highly infected.”

That’s important, he said, because an immune cell, which is supposed to fight the virus, is infected in the tissue. Also, the germ cell, responsible for sperm production, is infected.

“This reopens the worries about the presence of SARS-CoV-2 in semen, as other authors mentioned,” he said.
 

New findings

The team also found that the testes are a good place for viral replication.

The authors say they are the first to show:

• The longer the severe condition, the lower the number of surviving germ cells.
• There was fluctuation in several essential testicular genes.
• The intratesticular testosterone levels are 30 times reduced in the testes of COVID-19 patients.

The control group was composed of six patients who had undergone testicle removal after prostate cancer was suspected. Collection of both testicles from the test group was performed within 3 hours of death after a family member signed an informed consent document.

Recent research on semen demonstrates that patients who recovered from COVID-19 reestablish their sperm quality after 3 months of infection.

That study, in Fertility and Sterility, found that sperm quality was initially reduced for months in some men after recovery from COVID-19.

The team studied semen samples from 120 Belgian men (mean age, 35 years) at an average 52 days after their last COVID-19 symptoms. The semen was not found to be infectious.

But among 35 men who provided samples within a month after infection, reductions in sperm motility were evident in 60% and sperm counts were reduced in 37%, according to the report.
 

Testicular damage

The results [of the Costa et al. paper] emphasize the importance of testicular damage in severe COVID-19,” Rafael Kroon Campos, PhD, a postdoctoral fellow in the department of microbiology & immunology at the University of Texas Medical Branch at Galveston, said in an interview.

He noted that other viruses have also been shown to infect or otherwise cause testicular damage or orchitis, such as Zika, Ebola, and the closely related SARS-CoV-1. Sexual transmission has been documented for Zika and Ebola viruses.

Dr. Campos said with SARS-CoV-2, it is unclear whether sexual transmission plays a role.

“Some reports found evidence of viral RNA in semen, but these were rare occurrences. The study by Costa and colleagues used a combination of sensitive techniques and they were able to detect a small amount of viral RNA and viral protein in the testicular tissue of the deceased patients, as well as show viral factories indicating replication of the virus by electron microscopy,” he said.

Dr. Campos said the findings are particularly important and concerning because of the large number of severe cases of COVID-19.

“It is critical to continue to investigate the impact of the disease in testes, including the impact of different variants of concern on testicular damage,” he said.

Dr. McNeil and Dr. Campos have disclosed no relevant financial relationships.

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

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Violence against women remains a global dilemma in need of attention. Physical violence in particular, is the most prevalent type of violence across all genders, races, and nationalities.

The Centers for Disease Control and Prevention says more than 43 million women and 38 million men report experiencing psychological aggression by an intimate partner in their lifetime. Meanwhile, 11 million women and 5 million men report enduring sexual or physical violence and intimate partner violence (IPV), and/or stalking by an intimate partner during their lifetimes, according to the CDC.1

COVID pandemic’s influence

Isolation tied to the COVID-19 pandemic has been linked to increased IPV. A study conducted by researchers at the University of California, Davis, suggested that extra stress experienced during the COVID-19 pandemic caused by income loss, and the inability to pay for housing and food exacerbated the prevalence of IPV early during the pandemic.⁶

That study, where researchers collected in surveys of nearly 400 adults in the beginning in April 2020 for 10 weeks, showed that more services and communication are needed so that frontline health care and food bank workers, for example, in addition to social workers, doctors, and therapists, can spot the signs and ask clients questions about potential IPV. They could then link survivors to pertinent assistance and resources.

Furthermore, multiple factors probably have played a pivotal role in increasing the prevalence of IPV during the COVID-19 pandemic. For instance, disruption to usual health and social services as well as diminished access to support systems, such as shelters, and charity helplines negatively affected the reporting of domestic violence.

Long before the pandemic, over the past decade, international and national bodies have played a crucial role in terms of improving the awareness and response to domestic violence.^7,8 In addition, several policies have been introduced in countries around the globe emphasizing the need to inquire routinely about domestic violence. Nevertheless, mental health services often fail to adequately address domestic violence in clinical encounters. A systematic review of domestic violence assessment screening performed in a variety of health care settings found that evidence was insufficient to conclude that routine inquiry improved morbidity and mortality among victims of IPV.⁹ So the question becomes: How can we get our patients to tell us about these experiences so we can intervene?
 

Gender differences in perpetuating IPV

Several studies have found that abuse can result in various mental illnesses, such as depression, PTSD, anxiety, and suicidal ideation. Again, men have a disproportionately higher rate of perpetrating IPV, compared with women. This theory has been a source of debate in the academic community for years, but recent research has confirmed that women do perpetuate violence against their partners to some extent.^10,11

Some members of the LGBTQ+ community also report experiencing violence from partners, so as clinicians, we also need to raise our awareness about the existence of violence among same-sex couples. In fact, a team of Italian researchers report more than 50% of gay men and almost 75% of lesbian women reported that they had been psychologically abused by a partner.¹² More research into this area is needed.
 

Our role as health care professionals

The U.S. Preventive Services Task Force advises that all clinic visits include regular IPV screening.¹³ But these screenings are all too rare. In fact, a meta-analysis of 19 trials of more than 1,600 participants showed only 9%-40% of doctors routinely test for IPV.¹⁴ That research clearly shows how important it is for all clinicians to execute IPV screening. However, numerous challenges toward screening exist, including personal discomfort, limited time during appointments, insufficient resources, and inadequate training.

One ongoing debate revolves around which clinician should screen for IPV. Should the psychiatrist carry out this role – or perhaps the primary care physician, nurse, or social worker? These issues become even more fraught when clinicians worry about offending the patient – especially if the clinician is a male.¹⁵

The bottom line is that physicians should inquire about intimate partner violence, because research indicates that women are more likely to reveal abuse when prompted. In addition, during physician appointments, they can use the physician-patient therapeutic connection to conduct a domestic violence evaluation, give resources to victims, and provide ongoing care. Patients who exhibit treatment resistance, persistent pain, depression, sleeplessness, and headaches should prompt psychiatrists to conduct additional investigations into the likelihood of intimate partner violence and domestic abuse.

W also should be attentive when counseling patients about domestic violence when suggesting life-changing events such as pregnancy, employment loss, separation, or divorce. Similar to the recommendations of the USPSTF that all women and men should be screened for IPV, it is suggested that physicians be conscious of facilitating a conversation and not being overtly judgmental while observing body cues. Using the statements such as “we have been hearing a lot of violence in our community lately” could be a segue to introduce the subject.

Asking the question of whether you are being hit rather than being abused has allowed more women to open up more about domestic violence. While physicians are aware that most victims might recant and often go back to their abusers, victims need to be counseled that the abuse might intensify and lead to death.

For women who perpetuate IPV and survivors of IPV, safety is the priority. Physicians should provide safety options and be the facilitators. Studies have shown that fewer victims get the referral to the supporting agencies when IPV is indicated, which puts their safety at risk. In women who commit IPV, clinicians should assess the role of the individual in an IPV disclosure. There are various treatment modalities, whether the violence is performed through self-defense, bidirectionally, or because of aggression.

With the advancement of technology, web-based training on how to ask for IPV, documentation, acknowledgment, and structured referral increase physicians’ confidence when faced with an IPV disclosure than none.¹⁶ Treatment modalities should include medication reconciliation and cognitive-behavioral therapy – focusing on emotion regulation.

Using instruments such as the danger assessment tool can help physicians intervene early, reducing the risk of domestic violence and IPV recurrence instead of using clinical assessment alone.¹⁷ Physicians should convey empathy, validate victims, and help, especially when abuse is reported.

Also, it is important to evaluate survivors’ safety. Counseling can help people rebuild their self-esteem. Structured referrals for psychiatric help and support services are needed to help survivors on the long road to recovery.

Training all physicians, regardless of specialty, is essential to improve prompt IPV identification and bring awareness to resources available to survivors when IPV is disclosed. Although we described an association between IPV victims becoming possible perpetrators of IPV, more long-term studies are required to show the various processes that influence IPV perpetration rates, especially by survivors.

We would also like international and national regulatory bodies to increase the awareness of IPV and adequately address IPV with special emphasis on how mental health services should assess, identify, and respond to services for people who are survivors and perpetrators of IPV.

Dr. Kumari, Dr. Otite, Dr. Afzal, Dr. Alcera, and Dr. Doumas are affiliated with Hackensack Meridian Health at Ocean Medical Center, Brick, N.J. They have no conflicts of interest.

References

1. Centers for Disease Control and Prevention. Preventing intimate partner violence. 2020 Oct 9.

2. Yu R et al. PLOS Med. 16(12):e1002995. doi: 10.1371/journal.pmed.1002995.

3. Oram S et al. Epidemiol Psychiatr Sci. 2014 Dec;23(4):361-76.

4. Munro OE and Sellbom M. Pers Ment Health. 2020 Mar 11. doi: 10.1002/pmh.1480.

5. Sahraian A et al. Asian J Psychiatry. 2020 Jun. doi: 10.1016/j.ajp.2020.102062.

6. Nikos-Rose K. “COVID-19 Isolation Linked to Increased Domestic Violence, Researchers Suggest.” 2021 Feb 24. University of California, Davis.

7. World Health Organization. “Responding to intimate partner violence and sexual violence against women.” WHO clinical policy guidelines. 2013.

8. National Institute for Health and Care Excellence. “Domestic violence and abuse: Multi-agency working.” PH50. 2014 Feb 26.

9. Feder GS et al. Arch Intern Med. 2006;166(1):22-37.

10. Gondolf EW. Violence Against Women. 2014 Dec;20(12)1539-46.

11. Hamberger LK and Larsen SE. J Fam Violence. 2015;30(6):699-717.

12. Rollè L et al. Front Psychol. 21 Aug 2018. doi: 10.3389/fpsyg.2018.01506.

13. Paterno MT and Draughon JE. J Midwif Women Health. 2016;61(31):370-5.

14. Kalra N et al. Cochrane Database Syst Rev. 2021 May 31;5(5)CD012423.

15. Larsen SE and Hamberger LK. J Fam Viol. 2015;30:1007-30.

16. Kalra N et al. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD012423.

17. Campbell JC et al. J Interpers Violence. 2009;24(4):653-74.

Evidence summary

Alone or in combination with hCG, clomiphene citrate is effective

A 2018 multicenter prospective RCT (n = 283) compared the serum testosterone response in men (mean age, 41.8 ± 10.4 years) with hypogonadism before and after treatment with either CC, human chorionic gonadotropin (hCG), or a combination of both therapies.¹ All patients wanted to maintain fertility, had normal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, had no history of testosterone therapy, had low (< 300 ng/dL) serum testosterone levels on at least 2 samples, and had at least 3 positive symptoms from the quantitative Androgen Deficiency in the Aging Male questionnaire (qADAM; a 10-item, graded-response tool measuring symptom severity from 1 to 5).

Patients were randomized into either the CC group (50 mg oral; n = 95), the hCG group (5000 IU injections twice weekly; n = 94), or the CC + hCG group (n = 94). Testosterone levels were measured at baseline and at 1 and 3 months after therapy initiation; qADAM questionnaire scores were also recorded but ultimately not used due to concerns with baseline heterogeneity among groups.

Average baseline serum testosterone levels for the CC, hCG, and CC + hCG groups were 243 ng/dL, 222 ng/dL, and 226 ng/dL, respectively. By 3 months, these levels had increased to 548 ng/dL (95% CI, 505-591) in the CC group, 467 ng/dL (95% CI, 440-494) in the hCG group, and 531 ng/dL (95% CI, 492-570) in the CC + hCG group. While there was not a significant difference between the CC and CC + hCG groups at 3 months (P = .579), both groups were superior to the hCG-only group (P = .002 for each).

CC and testosterone gel are comparable; testosterone injection is better

In a 2014 retrospective study, researchers reviewed the charts of 1150 men taking any form of testosterone supplementation therapy (TST). They compared treatment efficacy and qADAM satisfaction scores in 93 age-matched men with symptomatic hypogonadism who were treated with either CC (n = 31), testosterone injections (n = 31), or testosterone topical gel (n = 31).² Eugonadal men not taking TST (n = 31) served as controls.

Inclusion criteria were based on treatment regimens of CC and TST. Participants in the treatment groups had a baseline total testosterone level < 300 ng/dL and had reported ≤ 3 positive symptoms on the qADAM questionnaire. Treatment regimens included CC (25 mg orally once daily), testosterone injections (testosterone cypionate 100 to 200 mg intramuscularly once weekly), and testosterone gel (Testim 1% or AndroGel 1.62%, 2 to 4 pumps/d).

The study results demonstrated an increase in median testosterone from baseline levels in all treatment groups when compared to placebo: CC (from 247 to 504 ng/dL), testosterone injections (from 224 to 1104 ng/dL), and testosterone gels (from 230 to 412 ng/dL) (P < .05). Men receiving testosterone injections had the highest increase in serum testosterone levels (956 ng/dL).

While the final mean serum total testosterone was highest in the testosterone injection group (1014 ng/dL; P < .01), the mean levels for those using CC and those using testosterone gels were comparable (525 ng/dL vs 412 ng/dL). Serum estradiol levels were also higher in men receiving testosterone injections, compared to men using CC, those using testosterone gels, and those not receiving TST (6.0 vs 2.0, 2.0, and 2.0 ng/dL, respectively; each P < .01).

Continue to: The qADAM scores...

The qADAM scores for hypogonadal symptoms showed no significant difference in men treated with CC, testosterone injections, and testosterone gels and those not receiving TST (35, 39, 36, and 34, respectively). Men receiving testosterone injections reported greater libido (range, 1-5) than men using CC, those using testosterone gels, and those not on TST (4 vs 3, 3, and 3; P = .047, .04, and < .01, respectively), but it is uncertain if this is clinically meaningful.

Enclomiphene citrate demonstrates improvement in hormone levels

A 2014 Phase II RCT investigated the effects of oral EC—a trans-isomer of CC—compared to topical testosterone 1% gel (T gel) in 124 men with secondary hypogonadism.³ Entry criteria included a baseline morning total testosterone level of < 250 ng/dL on 2 occasions. Participants were divided into 4 groups: 12.5-mg dose of EC, 25-mg dose of EC, T gel, and placebo.

The EC groups and the T gel group had comparable increases in testosterone levels after 3 months of treatment, without statistical significance. The 3-month change in serum testosterone level from baseline was 217 to 471 ng/dL (95% CI, 399-543) in the 12.5-mg dose group; 209 to 405 ng/dL (95% CI, 349-462) in the 25-mg dose group; and 210 to 462 ng/dL (95% CI, 359-565) in the T gel group. The placebo group had a decrease in serum testosterone levels, from 213 to 198 ng/dL (95% CI, 171-226).

Men with low or low-normal serum luteinizing hormone levels may be good candidates for the use of SERMs for management of testosterone deficiency.

Also, the EC groups demonstrated increases in LH and FSH levels from baseline to 3 months, while the T gel group showed a suppression (to low-normal range) in both levels: LH, 1.4 mIU/mL (decrease of 4.4 mIU/mL) and FSH, 2.4 mIU/mL (decrease of 2.4 mIU/mL). Among a subset of men (n = 67) who had at least 2 assessments at the end of 3 months, the researchers also analyzed changes in sperm concentration, using the lower limit of normal (15 million/mL). The number of men with a low sperm concentration increased significantly in the topical T gel group (16% to 53%) compared to the 12.5-mg EC group (decrease from 16% to 12%; P = .0008) and the 25-mg EC group (decrease from 5% to 0%; P = .0007), as well as compared to the placebo group (increase from 8% to 15%; P = .007).

With EC, testosterone remains elevated after treatment cessation

A 2016 2-center parallel, double-blind, ­placebo-controlled RCT evaluated the effect of 2 doses of EC (12.5 mg and 25 mg; n = 85) vs testosterone gel (1.62%; n = 85) vs placebo (n = 86) on serum testosterone, LH, FSH, and sperm counts in 256 overweight and obese men ages 18 to 60 years who had 2 morning testosterone measurements < 300 ng/dL and a low or inappropriately normal LH level for 16 weeks.⁴ All baseline characteristics, including age, BMI, sperm concentration, and serum total testosterone were statistically consistent within groups at both centers. For men receiving EC who did not achieve a testosterone level > 450 ng/dL, there was an up-titration from 12.5 mg to 25 mg at Week 4.

Continue to: All active treatment groups...

All active treatment groups showed increases in testosterone level during treatment (P < .001); however, FSH and LH levels increased in the EC group and decreased in the testosterone gel group (P < .001). Serum testosterone levels improved to 428.8 ng/dL (95% CI, 395-462) and 368.8 ng/dL (95% CI, 307-431), respectively, in the combined EC and testosterone gel groups at 16 weeks. Of note, total testosterone levels after cessation of treatment (off-drug point) rapidly decreased below baseline in the testosterone gel group compared to the pooled EC group, which remained elevated above baseline for at least 7 days.

Composite end-point analysis was performed, with success considered if men achieved both testosterone in normal range (300-1040 ng/dL) and sperm concentrations ≥ 10 × 10⁶. The pooled data studies showed EC was more successful than testosterone gel in achieving both endpoints (63.5% vs 24.7%; P < .001). No difference in the incidence of treatment-related adverse effects between groups was noted.

There were no major adverse effects, even after 3+ years of treatment

A 2019 retrospective cohort study of 400 men treated for symptomatic hypogonadism with CC sought to determine if improvements in testosterone, hypogonadal symptoms, and adverse effects were similar for those treated for ≤ 3 years (n = 280) and those treated for > 3 years (n = 120).⁵ Outcomes included serum testosterone and estradiol levels, symptom improvement (by qADAM questionnaire), and adverse effects.

All participants had a baseline testosterone level < 300 ng/dL, and all participants received CC therapy. Men received 25 mg/d with titration to 50 mg/d when testosterone did not improve to ≥ 300 ng/dL after 4 weeks.

When comparing outcomes across the 2 groups, there were no significant differences. Serum testosterone levels improved to 579 ng/dL (95% CI, 554-605) and 542 ng/dL (95% CI, 504-580) in the ≤ 3 years and > 3 years groups, respectively. Meanwhile, 79% of men in the ≤ 3 years group reported symptom improvement (improvement in libido, erection, or 3 other of the 10 domains of the qADAM questionnaire), while 77% of those in the > 3 years group reported improvement (P = .60).

Continue to: Finally, the percentage of men reporting...

Finally, the percentage of men reporting adverse effects did not significantly differ between groups: 9% in the ≤ 3 years group and 8% in the > 3 years group (P = .85). The most common adverse effects reported in order of frequency were mood changes, blurred vision, breast tenderness, hypertension, hematocrit changes, and flushing. No major adverse events (eg, myocardial infarction, cerebrovascular accident, venous thromboembolism, suicidal behavior) were reported in any patients.

Both the American Urological Association and the Canadian Urological Association support the use of SERMs, especially in hypogonadal men who are interested in fertility preservation.

Of note, although measured estrogen levels at the end of treatment were similar for both groups (54.8 pg/mL in the ≤ 3 years group vs 54.6 pg/mL in the > 3 years group), 37% of patients treated for > 3 years did receive anastrozole treatment for hyperestrogenism compared to 15% in the ≤ 3 years group (P = .05). The authors caution, though, that due to only 20% of the cohort patients having data on pre- and post-treatment estradiol levels, the study was likely underpowered to detect true differences among subgroups.

Recommendations from others

Current American Urological Association and Canadian Urological Association Guidelines note that while greater study on nontraditional testosterone therapies is needed, both organizations support use of SERMs, especially in hypogonadal men who are interested in fertility preservation, as increases in endogenous serum testosterone production do not impact fertility potential, unlike exogenous hormonal replacement.^6,7 Additionally, men with low or low-normal serum LH levels may also be good candidates for the use of SERMs for management of testosterone deficiency.

Editor’s takeaway

Laboratory data (disease oriented) consistently shows that SERMs effectively increase testosterone levels to those comparable with testosterone gels. SERMs resulted in higher semen counts and maintained LH and FSH levels, but there were instances of hyperestrogenism. Data on longer-term benefits and adverse effects of both SERMs and testosterone supplementation are still needed.

Evidence summary

Alone or in combination with hCG, clomiphene citrate is effective

A 2018 multicenter prospective RCT (n = 283) compared the serum testosterone response in men (mean age, 41.8 ± 10.4 years) with hypogonadism before and after treatment with either CC, human chorionic gonadotropin (hCG), or a combination of both therapies.¹ All patients wanted to maintain fertility, had normal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, had no history of testosterone therapy, had low (< 300 ng/dL) serum testosterone levels on at least 2 samples, and had at least 3 positive symptoms from the quantitative Androgen Deficiency in the Aging Male questionnaire (qADAM; a 10-item, graded-response tool measuring symptom severity from 1 to 5).

Patients were randomized into either the CC group (50 mg oral; n = 95), the hCG group (5000 IU injections twice weekly; n = 94), or the CC + hCG group (n = 94). Testosterone levels were measured at baseline and at 1 and 3 months after therapy initiation; qADAM questionnaire scores were also recorded but ultimately not used due to concerns with baseline heterogeneity among groups.

Average baseline serum testosterone levels for the CC, hCG, and CC + hCG groups were 243 ng/dL, 222 ng/dL, and 226 ng/dL, respectively. By 3 months, these levels had increased to 548 ng/dL (95% CI, 505-591) in the CC group, 467 ng/dL (95% CI, 440-494) in the hCG group, and 531 ng/dL (95% CI, 492-570) in the CC + hCG group. While there was not a significant difference between the CC and CC + hCG groups at 3 months (P = .579), both groups were superior to the hCG-only group (P = .002 for each).

CC and testosterone gel are comparable; testosterone injection is better

In a 2014 retrospective study, researchers reviewed the charts of 1150 men taking any form of testosterone supplementation therapy (TST). They compared treatment efficacy and qADAM satisfaction scores in 93 age-matched men with symptomatic hypogonadism who were treated with either CC (n = 31), testosterone injections (n = 31), or testosterone topical gel (n = 31).² Eugonadal men not taking TST (n = 31) served as controls.

Inclusion criteria were based on treatment regimens of CC and TST. Participants in the treatment groups had a baseline total testosterone level < 300 ng/dL and had reported ≤ 3 positive symptoms on the qADAM questionnaire. Treatment regimens included CC (25 mg orally once daily), testosterone injections (testosterone cypionate 100 to 200 mg intramuscularly once weekly), and testosterone gel (Testim 1% or AndroGel 1.62%, 2 to 4 pumps/d).

The study results demonstrated an increase in median testosterone from baseline levels in all treatment groups when compared to placebo: CC (from 247 to 504 ng/dL), testosterone injections (from 224 to 1104 ng/dL), and testosterone gels (from 230 to 412 ng/dL) (P < .05). Men receiving testosterone injections had the highest increase in serum testosterone levels (956 ng/dL).

While the final mean serum total testosterone was highest in the testosterone injection group (1014 ng/dL; P < .01), the mean levels for those using CC and those using testosterone gels were comparable (525 ng/dL vs 412 ng/dL). Serum estradiol levels were also higher in men receiving testosterone injections, compared to men using CC, those using testosterone gels, and those not receiving TST (6.0 vs 2.0, 2.0, and 2.0 ng/dL, respectively; each P < .01).

Continue to: The qADAM scores...

The qADAM scores for hypogonadal symptoms showed no significant difference in men treated with CC, testosterone injections, and testosterone gels and those not receiving TST (35, 39, 36, and 34, respectively). Men receiving testosterone injections reported greater libido (range, 1-5) than men using CC, those using testosterone gels, and those not on TST (4 vs 3, 3, and 3; P = .047, .04, and < .01, respectively), but it is uncertain if this is clinically meaningful.

Enclomiphene citrate demonstrates improvement in hormone levels

A 2014 Phase II RCT investigated the effects of oral EC—a trans-isomer of CC—compared to topical testosterone 1% gel (T gel) in 124 men with secondary hypogonadism.³ Entry criteria included a baseline morning total testosterone level of < 250 ng/dL on 2 occasions. Participants were divided into 4 groups: 12.5-mg dose of EC, 25-mg dose of EC, T gel, and placebo.

The EC groups and the T gel group had comparable increases in testosterone levels after 3 months of treatment, without statistical significance. The 3-month change in serum testosterone level from baseline was 217 to 471 ng/dL (95% CI, 399-543) in the 12.5-mg dose group; 209 to 405 ng/dL (95% CI, 349-462) in the 25-mg dose group; and 210 to 462 ng/dL (95% CI, 359-565) in the T gel group. The placebo group had a decrease in serum testosterone levels, from 213 to 198 ng/dL (95% CI, 171-226).

Men with low or low-normal serum luteinizing hormone levels may be good candidates for the use of SERMs for management of testosterone deficiency.

Also, the EC groups demonstrated increases in LH and FSH levels from baseline to 3 months, while the T gel group showed a suppression (to low-normal range) in both levels: LH, 1.4 mIU/mL (decrease of 4.4 mIU/mL) and FSH, 2.4 mIU/mL (decrease of 2.4 mIU/mL). Among a subset of men (n = 67) who had at least 2 assessments at the end of 3 months, the researchers also analyzed changes in sperm concentration, using the lower limit of normal (15 million/mL). The number of men with a low sperm concentration increased significantly in the topical T gel group (16% to 53%) compared to the 12.5-mg EC group (decrease from 16% to 12%; P = .0008) and the 25-mg EC group (decrease from 5% to 0%; P = .0007), as well as compared to the placebo group (increase from 8% to 15%; P = .007).

With EC, testosterone remains elevated after treatment cessation

A 2016 2-center parallel, double-blind, ­placebo-controlled RCT evaluated the effect of 2 doses of EC (12.5 mg and 25 mg; n = 85) vs testosterone gel (1.62%; n = 85) vs placebo (n = 86) on serum testosterone, LH, FSH, and sperm counts in 256 overweight and obese men ages 18 to 60 years who had 2 morning testosterone measurements < 300 ng/dL and a low or inappropriately normal LH level for 16 weeks.⁴ All baseline characteristics, including age, BMI, sperm concentration, and serum total testosterone were statistically consistent within groups at both centers. For men receiving EC who did not achieve a testosterone level > 450 ng/dL, there was an up-titration from 12.5 mg to 25 mg at Week 4.

Continue to: All active treatment groups...

All active treatment groups showed increases in testosterone level during treatment (P < .001); however, FSH and LH levels increased in the EC group and decreased in the testosterone gel group (P < .001). Serum testosterone levels improved to 428.8 ng/dL (95% CI, 395-462) and 368.8 ng/dL (95% CI, 307-431), respectively, in the combined EC and testosterone gel groups at 16 weeks. Of note, total testosterone levels after cessation of treatment (off-drug point) rapidly decreased below baseline in the testosterone gel group compared to the pooled EC group, which remained elevated above baseline for at least 7 days.

Composite end-point analysis was performed, with success considered if men achieved both testosterone in normal range (300-1040 ng/dL) and sperm concentrations ≥ 10 × 10⁶. The pooled data studies showed EC was more successful than testosterone gel in achieving both endpoints (63.5% vs 24.7%; P < .001). No difference in the incidence of treatment-related adverse effects between groups was noted.

There were no major adverse effects, even after 3+ years of treatment

A 2019 retrospective cohort study of 400 men treated for symptomatic hypogonadism with CC sought to determine if improvements in testosterone, hypogonadal symptoms, and adverse effects were similar for those treated for ≤ 3 years (n = 280) and those treated for > 3 years (n = 120).⁵ Outcomes included serum testosterone and estradiol levels, symptom improvement (by qADAM questionnaire), and adverse effects.

All participants had a baseline testosterone level < 300 ng/dL, and all participants received CC therapy. Men received 25 mg/d with titration to 50 mg/d when testosterone did not improve to ≥ 300 ng/dL after 4 weeks.

When comparing outcomes across the 2 groups, there were no significant differences. Serum testosterone levels improved to 579 ng/dL (95% CI, 554-605) and 542 ng/dL (95% CI, 504-580) in the ≤ 3 years and > 3 years groups, respectively. Meanwhile, 79% of men in the ≤ 3 years group reported symptom improvement (improvement in libido, erection, or 3 other of the 10 domains of the qADAM questionnaire), while 77% of those in the > 3 years group reported improvement (P = .60).

Continue to: Finally, the percentage of men reporting...

Finally, the percentage of men reporting adverse effects did not significantly differ between groups: 9% in the ≤ 3 years group and 8% in the > 3 years group (P = .85). The most common adverse effects reported in order of frequency were mood changes, blurred vision, breast tenderness, hypertension, hematocrit changes, and flushing. No major adverse events (eg, myocardial infarction, cerebrovascular accident, venous thromboembolism, suicidal behavior) were reported in any patients.

Both the American Urological Association and the Canadian Urological Association support the use of SERMs, especially in hypogonadal men who are interested in fertility preservation.

Of note, although measured estrogen levels at the end of treatment were similar for both groups (54.8 pg/mL in the ≤ 3 years group vs 54.6 pg/mL in the > 3 years group), 37% of patients treated for > 3 years did receive anastrozole treatment for hyperestrogenism compared to 15% in the ≤ 3 years group (P = .05). The authors caution, though, that due to only 20% of the cohort patients having data on pre- and post-treatment estradiol levels, the study was likely underpowered to detect true differences among subgroups.

Recommendations from others

Current American Urological Association and Canadian Urological Association Guidelines note that while greater study on nontraditional testosterone therapies is needed, both organizations support use of SERMs, especially in hypogonadal men who are interested in fertility preservation, as increases in endogenous serum testosterone production do not impact fertility potential, unlike exogenous hormonal replacement.^6,7 Additionally, men with low or low-normal serum LH levels may also be good candidates for the use of SERMs for management of testosterone deficiency.

Editor’s takeaway

Laboratory data (disease oriented) consistently shows that SERMs effectively increase testosterone levels to those comparable with testosterone gels. SERMs resulted in higher semen counts and maintained LH and FSH levels, but there were instances of hyperestrogenism. Data on longer-term benefits and adverse effects of both SERMs and testosterone supplementation are still needed.

Evidence summary

Alone or in combination with hCG, clomiphene citrate is effective

A 2018 multicenter prospective RCT (n = 283) compared the serum testosterone response in men (mean age, 41.8 ± 10.4 years) with hypogonadism before and after treatment with either CC, human chorionic gonadotropin (hCG), or a combination of both therapies.¹ All patients wanted to maintain fertility, had normal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, had no history of testosterone therapy, had low (< 300 ng/dL) serum testosterone levels on at least 2 samples, and had at least 3 positive symptoms from the quantitative Androgen Deficiency in the Aging Male questionnaire (qADAM; a 10-item, graded-response tool measuring symptom severity from 1 to 5).

Patients were randomized into either the CC group (50 mg oral; n = 95), the hCG group (5000 IU injections twice weekly; n = 94), or the CC + hCG group (n = 94). Testosterone levels were measured at baseline and at 1 and 3 months after therapy initiation; qADAM questionnaire scores were also recorded but ultimately not used due to concerns with baseline heterogeneity among groups.

Average baseline serum testosterone levels for the CC, hCG, and CC + hCG groups were 243 ng/dL, 222 ng/dL, and 226 ng/dL, respectively. By 3 months, these levels had increased to 548 ng/dL (95% CI, 505-591) in the CC group, 467 ng/dL (95% CI, 440-494) in the hCG group, and 531 ng/dL (95% CI, 492-570) in the CC + hCG group. While there was not a significant difference between the CC and CC + hCG groups at 3 months (P = .579), both groups were superior to the hCG-only group (P = .002 for each).

CC and testosterone gel are comparable; testosterone injection is better

In a 2014 retrospective study, researchers reviewed the charts of 1150 men taking any form of testosterone supplementation therapy (TST). They compared treatment efficacy and qADAM satisfaction scores in 93 age-matched men with symptomatic hypogonadism who were treated with either CC (n = 31), testosterone injections (n = 31), or testosterone topical gel (n = 31).² Eugonadal men not taking TST (n = 31) served as controls.

Inclusion criteria were based on treatment regimens of CC and TST. Participants in the treatment groups had a baseline total testosterone level < 300 ng/dL and had reported ≤ 3 positive symptoms on the qADAM questionnaire. Treatment regimens included CC (25 mg orally once daily), testosterone injections (testosterone cypionate 100 to 200 mg intramuscularly once weekly), and testosterone gel (Testim 1% or AndroGel 1.62%, 2 to 4 pumps/d).

The study results demonstrated an increase in median testosterone from baseline levels in all treatment groups when compared to placebo: CC (from 247 to 504 ng/dL), testosterone injections (from 224 to 1104 ng/dL), and testosterone gels (from 230 to 412 ng/dL) (P < .05). Men receiving testosterone injections had the highest increase in serum testosterone levels (956 ng/dL).

While the final mean serum total testosterone was highest in the testosterone injection group (1014 ng/dL; P < .01), the mean levels for those using CC and those using testosterone gels were comparable (525 ng/dL vs 412 ng/dL). Serum estradiol levels were also higher in men receiving testosterone injections, compared to men using CC, those using testosterone gels, and those not receiving TST (6.0 vs 2.0, 2.0, and 2.0 ng/dL, respectively; each P < .01).

Continue to: The qADAM scores...

The qADAM scores for hypogonadal symptoms showed no significant difference in men treated with CC, testosterone injections, and testosterone gels and those not receiving TST (35, 39, 36, and 34, respectively). Men receiving testosterone injections reported greater libido (range, 1-5) than men using CC, those using testosterone gels, and those not on TST (4 vs 3, 3, and 3; P = .047, .04, and < .01, respectively), but it is uncertain if this is clinically meaningful.

Enclomiphene citrate demonstrates improvement in hormone levels

A 2014 Phase II RCT investigated the effects of oral EC—a trans-isomer of CC—compared to topical testosterone 1% gel (T gel) in 124 men with secondary hypogonadism.³ Entry criteria included a baseline morning total testosterone level of < 250 ng/dL on 2 occasions. Participants were divided into 4 groups: 12.5-mg dose of EC, 25-mg dose of EC, T gel, and placebo.

The EC groups and the T gel group had comparable increases in testosterone levels after 3 months of treatment, without statistical significance. The 3-month change in serum testosterone level from baseline was 217 to 471 ng/dL (95% CI, 399-543) in the 12.5-mg dose group; 209 to 405 ng/dL (95% CI, 349-462) in the 25-mg dose group; and 210 to 462 ng/dL (95% CI, 359-565) in the T gel group. The placebo group had a decrease in serum testosterone levels, from 213 to 198 ng/dL (95% CI, 171-226).

Men with low or low-normal serum luteinizing hormone levels may be good candidates for the use of SERMs for management of testosterone deficiency.

Also, the EC groups demonstrated increases in LH and FSH levels from baseline to 3 months, while the T gel group showed a suppression (to low-normal range) in both levels: LH, 1.4 mIU/mL (decrease of 4.4 mIU/mL) and FSH, 2.4 mIU/mL (decrease of 2.4 mIU/mL). Among a subset of men (n = 67) who had at least 2 assessments at the end of 3 months, the researchers also analyzed changes in sperm concentration, using the lower limit of normal (15 million/mL). The number of men with a low sperm concentration increased significantly in the topical T gel group (16% to 53%) compared to the 12.5-mg EC group (decrease from 16% to 12%; P = .0008) and the 25-mg EC group (decrease from 5% to 0%; P = .0007), as well as compared to the placebo group (increase from 8% to 15%; P = .007).

With EC, testosterone remains elevated after treatment cessation

A 2016 2-center parallel, double-blind, ­placebo-controlled RCT evaluated the effect of 2 doses of EC (12.5 mg and 25 mg; n = 85) vs testosterone gel (1.62%; n = 85) vs placebo (n = 86) on serum testosterone, LH, FSH, and sperm counts in 256 overweight and obese men ages 18 to 60 years who had 2 morning testosterone measurements < 300 ng/dL and a low or inappropriately normal LH level for 16 weeks.⁴ All baseline characteristics, including age, BMI, sperm concentration, and serum total testosterone were statistically consistent within groups at both centers. For men receiving EC who did not achieve a testosterone level > 450 ng/dL, there was an up-titration from 12.5 mg to 25 mg at Week 4.

Continue to: All active treatment groups...

All active treatment groups showed increases in testosterone level during treatment (P < .001); however, FSH and LH levels increased in the EC group and decreased in the testosterone gel group (P < .001). Serum testosterone levels improved to 428.8 ng/dL (95% CI, 395-462) and 368.8 ng/dL (95% CI, 307-431), respectively, in the combined EC and testosterone gel groups at 16 weeks. Of note, total testosterone levels after cessation of treatment (off-drug point) rapidly decreased below baseline in the testosterone gel group compared to the pooled EC group, which remained elevated above baseline for at least 7 days.

Composite end-point analysis was performed, with success considered if men achieved both testosterone in normal range (300-1040 ng/dL) and sperm concentrations ≥ 10 × 10⁶. The pooled data studies showed EC was more successful than testosterone gel in achieving both endpoints (63.5% vs 24.7%; P < .001). No difference in the incidence of treatment-related adverse effects between groups was noted.

There were no major adverse effects, even after 3+ years of treatment

A 2019 retrospective cohort study of 400 men treated for symptomatic hypogonadism with CC sought to determine if improvements in testosterone, hypogonadal symptoms, and adverse effects were similar for those treated for ≤ 3 years (n = 280) and those treated for > 3 years (n = 120).⁵ Outcomes included serum testosterone and estradiol levels, symptom improvement (by qADAM questionnaire), and adverse effects.

All participants had a baseline testosterone level < 300 ng/dL, and all participants received CC therapy. Men received 25 mg/d with titration to 50 mg/d when testosterone did not improve to ≥ 300 ng/dL after 4 weeks.

When comparing outcomes across the 2 groups, there were no significant differences. Serum testosterone levels improved to 579 ng/dL (95% CI, 554-605) and 542 ng/dL (95% CI, 504-580) in the ≤ 3 years and > 3 years groups, respectively. Meanwhile, 79% of men in the ≤ 3 years group reported symptom improvement (improvement in libido, erection, or 3 other of the 10 domains of the qADAM questionnaire), while 77% of those in the > 3 years group reported improvement (P = .60).

Continue to: Finally, the percentage of men reporting...

Finally, the percentage of men reporting adverse effects did not significantly differ between groups: 9% in the ≤ 3 years group and 8% in the > 3 years group (P = .85). The most common adverse effects reported in order of frequency were mood changes, blurred vision, breast tenderness, hypertension, hematocrit changes, and flushing. No major adverse events (eg, myocardial infarction, cerebrovascular accident, venous thromboembolism, suicidal behavior) were reported in any patients.

Both the American Urological Association and the Canadian Urological Association support the use of SERMs, especially in hypogonadal men who are interested in fertility preservation.

Of note, although measured estrogen levels at the end of treatment were similar for both groups (54.8 pg/mL in the ≤ 3 years group vs 54.6 pg/mL in the > 3 years group), 37% of patients treated for > 3 years did receive anastrozole treatment for hyperestrogenism compared to 15% in the ≤ 3 years group (P = .05). The authors caution, though, that due to only 20% of the cohort patients having data on pre- and post-treatment estradiol levels, the study was likely underpowered to detect true differences among subgroups.

Recommendations from others

Current American Urological Association and Canadian Urological Association Guidelines note that while greater study on nontraditional testosterone therapies is needed, both organizations support use of SERMs, especially in hypogonadal men who are interested in fertility preservation, as increases in endogenous serum testosterone production do not impact fertility potential, unlike exogenous hormonal replacement.^6,7 Additionally, men with low or low-normal serum LH levels may also be good candidates for the use of SERMs for management of testosterone deficiency.

Editor’s takeaway

Laboratory data (disease oriented) consistently shows that SERMs effectively increase testosterone levels to those comparable with testosterone gels. SERMs resulted in higher semen counts and maintained LH and FSH levels, but there were instances of hyperestrogenism. Data on longer-term benefits and adverse effects of both SERMs and testosterone supplementation are still needed.

Artificial intelligence (AI) performs as well as expert uropathologists – and in some cases better than general pathologists – in diagnosing and grading prostate cancer, suggests a new study.

AI has shown promise in the diagnosis and grading of prostate cancer. However studies so far have been siloed, “with limited proof for generalization across diverse multinational cohorts, representing one of the central barriers to implementation of AI algorithms in clinical practice,” the investigators wrote in Nature Medicine.

Wouter Bulten, from the Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands, and coauthors reported the outcomes of the international PANDA histopathology competition, in which 1,290 deep learning algorithm developers were challenged to come up with reproducible algorithms that could match the findings of human experts. Deep learning is a form of machine learning in which artificial neural networks “learn” from large datasets and apply that learning in a similar way to the human brain. At least one AI product for detecting prostate cancer – the Paige Prostate system – has already been approved for clinical use in the United States. The Food and Drug Administration authorized marketing it in September 2021, as an adjunct to – but not replacement for – pathologist review.

The developers of the new algorithms participating in the competition were given a set of 10,616 digitized prostate biopsies to learn from, then were tested against a panel of either one to six – depending on the country – experienced uropathologists on a set of 393 digitized slides. A selection of 15 teams were then invited to take part in a validation phase with an additional 1,616 slides.

Within the first 10 days of the competition, one algorithm already achieved greater than 0.90 agreement with the uropathologists; by day 33, the median performance of all the teams in the competition was greater than 0.85 agreement with the human experts.
 

Algorithms correctly detected tumors in 99.7% of cases

The algorithms selected for validation showed even higher levels of agreement – 0.931 on average (95% confidence interval, 0.918-0.944). These algorithms correctly detected tumors in 99.7% of cases (95% CI, 98.1%-99.7%), and correctly identified 92.9% of negative results (95% CI, 91.9%-96.7%).

When it came to classifying the prostate cancers based on Gleason grade, the algorithms showed significantly more agreement with uropathologists than did an international panel of 13 or 20 general pathologists.

“This higher sensitivity shows promise for reducing pathologist workload by automated identification and exclusion of most benign biopsies from review,” the authors wrote.

The study found that the AI algorithms missed 1%-1.9% of cancers, but the general pathologists missed 1.8%-7.3%. The algorithms demonstrated a sensitivity of 96.4%-98.2% and specificity of 75%-100% for tumors, whereas the pathologists showed a sensitivity of 91.9-96.5% and specificity of 92.3%-95%.
 

Benign cases were misclassified

The main error that the algorithms made was misclassifying benign cases as ISUP GG 1 cancer. The authors commented that this was likely caused by a shift in the distribution of cases between the training data given to the algorithms and the data set they were validated on.

They also noted that, in one validation set, the algorithms overgraded a “substantial proportion” of ISUP GG 3 cases as GG 4, whereas general pathologists tended to undergrade cases, particularly in the higher-grade cancers.

“These differences suggest that general pathologists supported by AI could reach higher agreements with uropathologists, potentially alleviating some of the rater variability associated with Gleason grading,” they wrote.

The authors also pointed out that the algorithms were validated on individual biopsies from each patient, whereas in the clinical context, a pathologist would likely have multiple biopsies from a single patient.

“Future studies can focus on patient-level evaluation of tissue samples, taking multiple cores and sections into account for the final diagnosis,” they wrote.

The study was supported by the Dutch Cancer Society, Netherlands Organization for Scientific Research, Google, Verily Life Sciences, Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health, Karolinska Institutet, Åke Wiberg Foundation, Prostatacancerförbundet, Academy of Finland, Cancer Foundation Finland, and ERAPerMed. The authors declared a range of grants and funding outside the study, including from Philips Digital Pathology Solutions. Several authors declared patents related to prostate cancer diagnoses, and 10 were employees of Google.

Artificial intelligence (AI) performs as well as expert uropathologists – and in some cases better than general pathologists – in diagnosing and grading prostate cancer, suggests a new study.

AI has shown promise in the diagnosis and grading of prostate cancer. However studies so far have been siloed, “with limited proof for generalization across diverse multinational cohorts, representing one of the central barriers to implementation of AI algorithms in clinical practice,” the investigators wrote in Nature Medicine.

Wouter Bulten, from the Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands, and coauthors reported the outcomes of the international PANDA histopathology competition, in which 1,290 deep learning algorithm developers were challenged to come up with reproducible algorithms that could match the findings of human experts. Deep learning is a form of machine learning in which artificial neural networks “learn” from large datasets and apply that learning in a similar way to the human brain. At least one AI product for detecting prostate cancer – the Paige Prostate system – has already been approved for clinical use in the United States. The Food and Drug Administration authorized marketing it in September 2021, as an adjunct to – but not replacement for – pathologist review.

The developers of the new algorithms participating in the competition were given a set of 10,616 digitized prostate biopsies to learn from, then were tested against a panel of either one to six – depending on the country – experienced uropathologists on a set of 393 digitized slides. A selection of 15 teams were then invited to take part in a validation phase with an additional 1,616 slides.

Within the first 10 days of the competition, one algorithm already achieved greater than 0.90 agreement with the uropathologists; by day 33, the median performance of all the teams in the competition was greater than 0.85 agreement with the human experts.
 

Algorithms correctly detected tumors in 99.7% of cases

The algorithms selected for validation showed even higher levels of agreement – 0.931 on average (95% confidence interval, 0.918-0.944). These algorithms correctly detected tumors in 99.7% of cases (95% CI, 98.1%-99.7%), and correctly identified 92.9% of negative results (95% CI, 91.9%-96.7%).

When it came to classifying the prostate cancers based on Gleason grade, the algorithms showed significantly more agreement with uropathologists than did an international panel of 13 or 20 general pathologists.

“This higher sensitivity shows promise for reducing pathologist workload by automated identification and exclusion of most benign biopsies from review,” the authors wrote.

The study found that the AI algorithms missed 1%-1.9% of cancers, but the general pathologists missed 1.8%-7.3%. The algorithms demonstrated a sensitivity of 96.4%-98.2% and specificity of 75%-100% for tumors, whereas the pathologists showed a sensitivity of 91.9-96.5% and specificity of 92.3%-95%.
 

Benign cases were misclassified

The main error that the algorithms made was misclassifying benign cases as ISUP GG 1 cancer. The authors commented that this was likely caused by a shift in the distribution of cases between the training data given to the algorithms and the data set they were validated on.

They also noted that, in one validation set, the algorithms overgraded a “substantial proportion” of ISUP GG 3 cases as GG 4, whereas general pathologists tended to undergrade cases, particularly in the higher-grade cancers.

“These differences suggest that general pathologists supported by AI could reach higher agreements with uropathologists, potentially alleviating some of the rater variability associated with Gleason grading,” they wrote.

The authors also pointed out that the algorithms were validated on individual biopsies from each patient, whereas in the clinical context, a pathologist would likely have multiple biopsies from a single patient.

“Future studies can focus on patient-level evaluation of tissue samples, taking multiple cores and sections into account for the final diagnosis,” they wrote.

The study was supported by the Dutch Cancer Society, Netherlands Organization for Scientific Research, Google, Verily Life Sciences, Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health, Karolinska Institutet, Åke Wiberg Foundation, Prostatacancerförbundet, Academy of Finland, Cancer Foundation Finland, and ERAPerMed. The authors declared a range of grants and funding outside the study, including from Philips Digital Pathology Solutions. Several authors declared patents related to prostate cancer diagnoses, and 10 were employees of Google.

Artificial intelligence (AI) performs as well as expert uropathologists – and in some cases better than general pathologists – in diagnosing and grading prostate cancer, suggests a new study.

AI has shown promise in the diagnosis and grading of prostate cancer. However studies so far have been siloed, “with limited proof for generalization across diverse multinational cohorts, representing one of the central barriers to implementation of AI algorithms in clinical practice,” the investigators wrote in Nature Medicine.

Wouter Bulten, from the Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands, and coauthors reported the outcomes of the international PANDA histopathology competition, in which 1,290 deep learning algorithm developers were challenged to come up with reproducible algorithms that could match the findings of human experts. Deep learning is a form of machine learning in which artificial neural networks “learn” from large datasets and apply that learning in a similar way to the human brain. At least one AI product for detecting prostate cancer – the Paige Prostate system – has already been approved for clinical use in the United States. The Food and Drug Administration authorized marketing it in September 2021, as an adjunct to – but not replacement for – pathologist review.

The developers of the new algorithms participating in the competition were given a set of 10,616 digitized prostate biopsies to learn from, then were tested against a panel of either one to six – depending on the country – experienced uropathologists on a set of 393 digitized slides. A selection of 15 teams were then invited to take part in a validation phase with an additional 1,616 slides.

Within the first 10 days of the competition, one algorithm already achieved greater than 0.90 agreement with the uropathologists; by day 33, the median performance of all the teams in the competition was greater than 0.85 agreement with the human experts.
 

Algorithms correctly detected tumors in 99.7% of cases

The algorithms selected for validation showed even higher levels of agreement – 0.931 on average (95% confidence interval, 0.918-0.944). These algorithms correctly detected tumors in 99.7% of cases (95% CI, 98.1%-99.7%), and correctly identified 92.9% of negative results (95% CI, 91.9%-96.7%).

When it came to classifying the prostate cancers based on Gleason grade, the algorithms showed significantly more agreement with uropathologists than did an international panel of 13 or 20 general pathologists.

“This higher sensitivity shows promise for reducing pathologist workload by automated identification and exclusion of most benign biopsies from review,” the authors wrote.

The study found that the AI algorithms missed 1%-1.9% of cancers, but the general pathologists missed 1.8%-7.3%. The algorithms demonstrated a sensitivity of 96.4%-98.2% and specificity of 75%-100% for tumors, whereas the pathologists showed a sensitivity of 91.9-96.5% and specificity of 92.3%-95%.
 

Benign cases were misclassified

The main error that the algorithms made was misclassifying benign cases as ISUP GG 1 cancer. The authors commented that this was likely caused by a shift in the distribution of cases between the training data given to the algorithms and the data set they were validated on.

They also noted that, in one validation set, the algorithms overgraded a “substantial proportion” of ISUP GG 3 cases as GG 4, whereas general pathologists tended to undergrade cases, particularly in the higher-grade cancers.

“These differences suggest that general pathologists supported by AI could reach higher agreements with uropathologists, potentially alleviating some of the rater variability associated with Gleason grading,” they wrote.

The authors also pointed out that the algorithms were validated on individual biopsies from each patient, whereas in the clinical context, a pathologist would likely have multiple biopsies from a single patient.

“Future studies can focus on patient-level evaluation of tissue samples, taking multiple cores and sections into account for the final diagnosis,” they wrote.

The study was supported by the Dutch Cancer Society, Netherlands Organization for Scientific Research, Google, Verily Life Sciences, Swedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health, Karolinska Institutet, Åke Wiberg Foundation, Prostatacancerförbundet, Academy of Finland, Cancer Foundation Finland, and ERAPerMed. The authors declared a range of grants and funding outside the study, including from Philips Digital Pathology Solutions. Several authors declared patents related to prostate cancer diagnoses, and 10 were employees of Google.