Theory 1: Testosterone May Stimulate Production of Proteins That Affect Virus Activity
Studies have shown that testosterone can regulate production and activity of the protein receptor ACE2, which mediates entry of the virus into cells, and TMPRSS2, a co-receptor that activates the virus. “Research showed years ago that these proteins functioned in the same manner to facilitate the entry of SARS-CoV-1 into cells; current COVID-19 research is finding that these same proteins function the same ways with respect to SARS-CoV-2,” explains Jon E. Levine, PhD, a professor of neuroscience at the University of Wisconsin and the director of the Wisconsin National Primate Research Center in Madison. Dr. Levine was not involved in the study analysis. RELATED: Why 10 Feet May Be Better Than 6 Feet
Theory 2: Testosterone Levels Drop When Men Are Very Sick
When men are critically ill, their testosterone levels dramatically drop. Normal levels of testosterone are required to protect the functioning of cells in the lining of blood vessels (preventing blood clotting) and may protect against a defective immune response. “Having low testosterone levels because you are critically ill may impair your ability to clear the virus and promotes systemic inflammation,” says Dr. Levine. RELATED: Why Is the Coronavirus More Deadly for Men?
Theory 3: The Male Tendency to Belly Fat Increases Risk of Inflammation
Men tend to develop obesity in abdominal versus subcutaneous adipose tissue under the influence of androgenic hormones, such as testosterone. That abdominal, or belly fat, tissue generates more inflammatory cytokines, small proteins that are important in cell signaling. This is why males tend to have higher rates of diabetes, cardiovascular disease, atherosclerosis, metabolic syndrome, insulin resistance, and respiratory disease (asthma, bronchitis, emphysema, or chronic obstructive pulmonary disease). “If you’re a male with preexisting obesity and metabolic disease, when you get this virus in the lungs, you may be more vulnerable because you already have preexisting peripheral inflammation,” Levine explains. RELATED: What People With Heart Disease Need to Know About COVID-19
How Can Too Much Testosterone, and Too Little Testosterone, Both Increase Risk?
Welcome to the confusing and complicated world of hormones, Meredith W. Reiches, PhD, the assistant director of the GenderSci Lab at Harvard University in Boston, says in an email message. “Hormones can indeed have different effects in different doses, at different receptor sites, and in different endocrine contexts. For instance, estradiol, a form of estrogen, promotes bone growth during puberty when it binds with one kind of receptor, but, at a higher concentration, it causes the epiphyses [end part of a long bone] to fuse, ending bone growth, when it binds to a receptor that is only active at higher concentrations. So, while the theories in the Andrology study are in some ways difficult to reconcile, the effect of testosterone on the course of the disease could actually be different in different contexts.” Dr. Reiches was also not part of the study analysis.
Another View: Social Factors May Be More Important Than Biology
Dr. Reiches, who is also an assistant professor of anthropology at the University of Massachusetts in Boston, explains that the different effects of testosterone are a reason why “testosterone probably isn’t a panacea explanation for sex differences in outcomes.” She and her group at the GenderSci Lab believe that while it might be the case that sex-linked biological traits such as hormones contribute to the ways bodies respond to COVID-19, emerging case-fatality rate data from COVID-19 suggests that sex-linked biology is unlikely to be the primary driver of differences in outcomes between men and women. Among U.S. states and territories, as of June 22, 2020, 53 percent of reported deaths in Delaware are women, while in California, 56 percent are men. The team would have expected a more robust consistency in case-fatality rates by sex if, for instance, testosterone-linked differences in ACE2 expression and activity were the main determinant of how men and women respond to COVID-19.
Who Is Exposed, Likeliness to Seek Care, and Other Social Factors Are Key
Instead, Reiches reports in the same email message, “Observed variation suggests that, as with earlier coronavirus infections like SARS and MERS and prior pandemics like the 1918 Spanish flu, many social factors affect who is exposed to a virus, the viral dose of the exposure, their age and health at the time of infection, how likely they are to seek care, and how responsive and effective medical intervention might be. “Therefore, while we don’t rule out contributions from sex-linked biology, we advocate for data collection, disaggregation, and analysis of factors where public health, policy, and clinical workers can help make changes — say, in improving working and living conditions of people in poverty and people in caregiving roles, or investigating and treating causes of comorbidities in populations experiencing chronic and endemic racism,” says Reiches. “We have much to learn about how SARS-CoV-2 functions in the body,” Reiches concludes. “When it comes to identifying urgent targets for intervention, however, our research group argues, based on the available data and on precedent from similar pandemics, that attention to social factors will explain much of the variation in outcomes.” RELATED: The 8 Best Thing Dads Can Do for Their Health
