US Pharm. 2022;47(6):8-12.


Endocrine-Disrupting Chemicals May Impair Bone Health in Male Teens

Per- and polyfluoroalkyl substances (PFAS) and phthalates (two types of endocrine-disrupting chemicals) may be associated with lower bone mineral density in male teens, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.

Endocrine-disrupting chemicals are chemicals or mixtures of chemicals that interfere with the way the body’s hormones work. PFAS are synthetic chemicals used in nonstick cookware, clothing, and food packaging, and they are increasingly being found in U.S. water supplies. Phthalates are used in personal care products, food processing, and children’s toys.

“Adolescence is an important time when our bodies build up bone. Almost all U.S. children and adolescents are exposed to PFAS and phthalates, but few studies have looked at how these chemicals could be impacting our bone health,” said Abby F. Fleisch, MD, MPH, of the Maine Medical Center Research Institute and Maine Medical Center in Portland. “Our research found an association between certain PFAS and phthalates and reduced bone mineral density in adolescent males. Because bone accrual primarily occurs during adolescence, if replicated, this finding may have implications for lifelong bone health.”

The researchers leveraged urine and blood samples from 453 boys and 395 girls from the National Health and Nutrition Examination Survey and found higher levels of PFAS and phthalates may be associated with lower bone mineral density in adolescent males. The researchers did not find the same effect in girls.


Older Men With High BMI Have More Sperm Cell Irregularities

Single-cell analysis of autopsied human testes suggests that abnormalities associated with aging sperm cells might be exacerbated by elevated BMI. The research appeared in the journal Developmental Cell.

Even though it is well established that older men display reduced reproductive health, testis aging remains poorly understood at the molecular and genomic levels. Moreover, it has not been clear whether lifestyle or environmental factors affect this decline.

“Aging may confer a combination of modest molecular changes that sensitize the testis for additional dysregulation, with pronounced dysregulation caused when aging is combined with additional factors such as obesity,” says cosenior author Bradley Cairns of the University of Utah School of Medicine.

To address this gap, Dr. Cairns and cosenior study author Jingtao Guo, also of the University of Utah School of Medicine, used single-cell RNA sequencing to profile more than 44,000 cells obtained from autopsy testis samples from four young men and eight older men. The older donors were screened for having offspring as young adults to ensure early-adult fertility.

The young samples clustered together and did not display molecular signatures of aging or a disrupted ability to produce sperm cells. Surprisingly, the older samples showed only modest age-related changes in stem cells that give rise to mature sperm but were clearly classified into two distinct groups. The first group displayed an intact ability to produce sperm cells, with only weak molecular signatures that distinguished them from young samples. By contrast, the second group showed a very limited ability to develop sperm cells.

Notably, BMI emerged as a critical factor among older individuals. All donors from the first group had levels lower than 27, whereas all donors from the second group had levels higher than 30. Taken together, the results reveal possible molecular mechanisms underlying the complex testicular changes associated with aging, and their possible exacerbation by concurrent chronic conditions such as obesity.

Moving forward, larger patient cohorts are needed to fully validate the results. Another avenue for future research is to explore whether the testicular cells of older, heavy-set males show unique aging signatures or whether they simply display accelerated aging. It is also not clear whether diet, exercise, diabetes, or altered hormone production plays a role in testis aging. In addition, determining at what age the dysregulation of supporting testis cells emerges and whether and how it may be reversible may lead to the development of improved medical guidance for older men.

“Our study reveals potential biomarkers for diagnosis of testis aging and directions for potential treatment of aging-related subfertility,” says Dr. Guo. “It also serves as a foundational dataset for the scientific community to study how human testis and fertility respond to aging.”

This work was supported by the National Institute on Aging.

Study: COVID-19 Alters Fertility-Related Protein Levels in Me

Many people who recover from COVID-19 experience long-term symptoms, such as brain fog or heart problems. Increasing evidence suggests that the virus can also impair fertility. Researchers reporting in ACS Omega have analyzed protein levels in semen of men who have recovered from COVID-19. The pilot study suggests that even mild or moderate illness could change the levels of proteins related to male reproductive function, the researchers say.

Although SARS-CoV-2 mainly affects the respiratory system, the virus—and the body’s response to it—also damages other tissues. Recent evidence indicates that COVID-19 infection can reduce male fertility, and the virus has been detected in male reproductive organs. Firuza Parikh and Rajesh Parikh at Jaslok Hospital, Sanjeeva Srivastava at the Indian Institute of Technology, and colleagues wondered if COVID-19 infection could have long-term impacts on the male reproductive system. To find out, they decided to compare levels of proteins in the semen of healthy men and those who previously had mild or moderate cases of COVID-19.

The researchers analyzed semen samples from 10 healthy men and 17 men who had recently recovered from COVID-19. None of the men, who ranged in age from 20 to 45 years, had a prior history of infertility. The team found that the recovered men had significantly reduced sperm count and motility and fewer normally shaped sperm than men who had not had COVID-19. When the researchers analyzed semen proteins using liquid chromatography–tandem mass spectrometry, they found 27 proteins at higher levels and 21 proteins at lower levels in COVID-19–recovered men compared with the control group.

Many of the proteins were involved in reproductive function. Two of the fertility-related proteins, semenogelin 1 and prosaposin, were present at less than half their levels in the semen of the COVID-19–recovered group than in the semen of controls. These findings suggest that SARS-CoV-2 has direct or indirect effects on male reproductive health that linger after recovery, the researchers say. The work might also reveal insights into the pathophysiology of human reproduction in recovered men, they add. However, they note that larger studies should be done to confirm these findings, and a control group of men who recently recovered from other flu-like illnesses should be included to ensure that the findings are specific for COVID-19.

Men With High Blood Pressure Have a Biased Recognition of Other People’s Anger

Men with high blood pressure have a biased recognition of other people’s anger, as shown in a new study. Hypertension is a disease. However, in the majority of cases, there is no clear medical explanation, referred to as essential hypertension. Could psychological factors play a role? In this context, Konstanz biological health psychologists Alisa Auer and Professor Petra Wirtz conducted a study in male participants over several years together with colleagues from Konstanz (Germany) and Switzerland. The researchers wanted to better understand the psychobiosocial mechanisms in hypertension, since previous work in this area has left many questions open.

In an article published in the Annals of Behavioral Medicine, the researchers show that compared with a healthy control group, men with essential hypertension more often recognized angry expressions when they looked into the faces of others. In addition, this anger recognition bias seems to contribute to blood pressure increases over time if someone tends to frequently and intensively experience anger. This tendency is called trait anger.

In their study of 145 hypertensive and normotensive men, researchers presented different pictures of people who were angry. However, the pictures did not just display anger alone but combined anger with one of three other emotions: fear, happiness, and sadness. The background for this approach is that in everyday life, people’s faces rarely show just one emotion. Mixed emotions are more prevalent. Each of the computer-morphed pictures showed two emotions with varying affect intensities. Participants were asked which emotion they saw in the pictures.

“Hypertensive men recognized anger more often than any other emotion,” says Ms. Auer. “So, they overrated anger displayed in other people’s faces as compared to our healthy control group.” Dr. Wirtz adds, “Overrating anger displayed by other persons seems to affect whether high ‘trait anger’ contributes to blood pressure increases over time.” Hence, interpersonal factors seem to play a role in essential hypertension. The expectation of associations between hypertension and social aspects was one of the reasons why the study was supported by the Cluster of Excellence Centre for the Advanced Study of Collective Behaviour.

Ms. Auer and Dr. Wirtz hope that their results will be examined and confirmed by other researchers. “Then, a next step would be to offer people with essential hypertension a more targeted support,” says Ms. Auer, who is currently completing her doctorate in psychology. She is thinking of “therapeutic treatments that address a person’s perception of social environments in order to protect them from other people’s anger.”

Such therapeutic interventions would be important, because blood pressure–lowering medication only treats the consequences of hypertension, but it does not address potential causes. In addition, hypertension is one of the major risk factors for cardiovascular disease. In 2020, as in previous years, the Federal Statistical Office (Destatis) listed cardiovascular disease as the leading cause of death in Germany. Destatis reports that “338,001 deaths, or more than one third of all deaths (34%), can be attributed to cardiovascular disease.” Cardiovascular disease is especially deadly for older people: 93% of those who died of cardiovascular disease were aged 65 years or older.

What about women? The researchers hope that future studies will include women. Since women may possibly differ from men in their emotion recognition and as fewer women suffer from hypertension, the study initially focused on men.

Diabetes Origins May Differ in Men and Women

Over the past 4 decades, global cases of type 2 diabetes mellitus have skyrocketed. According to the World Health Organization, the number of people estimated to have the disease jumped from 108 million in 1980 to 422 million in 2014, with the fastest growth observed in low- and middle-income countries.

Although the disease is common, there is still much research left to be done to fully understand it. For instance, while diabetes is linked to obesity, researchers still do not know the exact reasons obesity causes diabetes.

In a paper in the journal Obesity Reviews, researchers Kerri Delaney and Sylvia Santosa from Concordia University, Montreal, looked at how fat tissue from different parts of the body may lead to diabetes onset in men and women. They reviewed almost 200 scientific papers looking for a deeper understanding of how fat operates at the surface and tissue level and the mechanisms by which that tissue contributes to diabetes onset.

“There are many different theories about how diabetes develops, and the one that we explore posits that different regions of fat tissue contributes to disease risk differently,” says Dr. Delaney, a PhD candidate at Concordia’s PERFORM Centre and the paper’s lead author. “So, the big question is, how do the different depots uniquely contribute to its development, and is this contribution different in men and women?”

Men and women store fat in different places. Diabetes, like many other diseases, is closely associated with abdominal fat. Women tend to store that fat just under the skin. This is known as subcutaneous fat. In men, abdominal fat is stored around the organs. This is visceral fat.

Fat appears to exhibit different features in men and women. Fat tissue grows differently, is dispersed differently, and interacts with the inflammatory and immune system differently. For example, in men fat tissue expands because the fat cells grow in size; in women, fat cells multiply and increase in number. This changes with the loss of the protective hormone estrogen that disappears with menopause and may explain why men are more susceptible to diabetes earlier in life than women.

Working from the hypothesis that diabetes risk is driven by expansions of visceral fat in men and of subcutaneous fat in women, the researchers then looked through the papers to see what was happening in the cell-level microenvironments. Although more research is needed, there were overall differences observed in the immune cell, hormone, and cell-signaling levels in men and women that seem to support different origins in diabetes between the sexes.

Drs. Delaney and Santosa hope that by identifying how diabetes risks are different in men and women, clinical approaches to treatment of the disease can be better defined between the sexes.

“Currently, the treatment of diabetes is similar for men and women,” says Dr. Santosa, an associate professor in the department of Health, Kinesiology and Applied Physiology. “If we understood the differences between them better, we could consider these mechanisms in recommending treatments to men and women based on how diabetes medications work.”

High Prevalence of Cancer Among Men Living With HIV, Study Shows

Researchers with Case Western Reserve University (CWRU) have found that there are nearly twice as many men with cancer among men living with HIV (MLWH) compared to men who do not have HIV. The rates of cancer are even higher in men with symptomatic HIV.

The researchers based their findings on national Medicaid data, which included more than 82,000 MLWH and more than 7 million men without HIV. The highest rates of cancer were for anal cancer in both symptomatic and asymptomatic MLWH. Additionally, the highest rates of cancer in MLWH were detected in Hispanic MLWH.

The study, Excess Cancer Prevalence in Men with HIV: A Nationwide Analysis of Medicaid Data, funded by the Case Comprehensive Cancer Center, was published in the online early view edition of Cancer, an American Cancer Society journal. The study was published with an accompanying editorial, “An ounce of prevention: Medicaid’s role in reducing the burden of cancer in men with HIV.”

“Medicaid plays a key role in insuring people with HIV,” said Siran Koroukian, a professor in the Department of Population and Quantitative Health Sciences at the CWRU School of Medicine and director of the Case Comprehensive Cancer Center’s Population Cancer Analytics Shared Resource. “Our findings highlight the importance of the Medicaid program’s efforts to promote healthy behaviors and to promote vaccine against human papillomavirus in children and adolescents, as well as individualized cancer screening.”

Dr. Koroukian was joined as co–lead author in this study by Guangjin Zhou, PhD, doctoral candidate in the CWRU Clinical Translational Science program, Center for Clinical Investigation, and also joined by coauthors Johnie Rose, MD, PhD, codirector of the Case Comprehensive Cancer Center’s Population Cancer Analytics Shared Resource, and Gregory S. Cooper, MD, MA, professor in CWRU’s Department of Medicine and co-leader, Case Comprehensive Cancer Center’s Cancer and Prevention Program.

The authors observed excess cancer prevalence for several cancer types in addition to anal cancer, including lymphoma and rectal cancers. They noted excess cancer prevalence is due in part to premature aging from HIV, as well as the prevalence of other (non-HIV) cancer risk factors, such as smoking and exposure to oncogenic viruses—including human papillomavirus (HPV)—known to cause certain cancers.

The accompanying editorial, written by Cathy J. Bradley, of the Colorado School of Public Health, and Lindsay M. Sabik, of the University of Pittsburgh School of Public Health, highlights the importance of addressing known risk factors and the need for continued use of antiretroviral therapies, as well as promoting HPV vaccination, even later in life.

The editorial also emphasizes the importance of using these findings to inform policy initiatives, including programs to ensure continuous enrollment in Medicaid and physician reimbursement policies to improve cancer screening, as well as controlling the cost of expensive medications to treat both conditions.

“Koroukian et al’s study is especially important because it reports on a growing population who experience the convergence of two previously fatal health conditions that are now becoming chronic conditions,” the editorial’s authors note.

As the editorialists further note, excess cancer prevalence in MLWH should be interpreted with the understanding that many people enroll in Medicaid once they are diagnosed with a catastrophic illness such as cancer. They highlight the importance of augmenting Medicaid data by linking with cancer registry data to learn more about when cancer is diagnosed relative to Medicaid enrollment and HIV diagnosis. Such a rich data infrastructure would facilitate the study of cancer stage at diagnosis and related survival outcomes, they conclude.

Men With High Body Fat Levels May Be at Risk for Osteoporosis

Men with high levels of body fat have lower bone density and may be more likely to break a bone than those with normal levels of body fat, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.

Most studies have shown positive or neutral effects of body fat mass—the weight of fat in your body—on bone health. Lean mass is the entire weight of one’s body, including organs, skin, and bones, minus fat. Healthcare providers often assume people with higher body weight have high bone density and are at low risk of fracture, and these patients are less likely to be screened for osteoporosis.

“We found that higher fat mass was related to lower bone density, and these trends were stronger in men than women,” said Rajesh K. Jain, MD, of University of Chicago Medicine in Chicago. “Our research suggests that the effect of body weight depends on a person’s makeup of lean and fat mass, and that high body weight alone is not a guarantee against osteoporosis.”

The researchers analyzed the bone mineral density and body composition data of 10,814 people aged younger than 60 years from the National Health and Nutrition Examination Survey 2011-2018. They found a strong positive association between lean mass and bone mineral density in both men and women. Conversely, fat mass had a moderately negative association with bone mineral density, especially in the findings in men.

“Healthcare providers should consider osteoporosis screening for patients with high body weight, especially if they have other risk factors like older age, previous fracture, family history, or steroid use,” Dr. Jain said.

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