The spread of the highly infectious disease COVID-19 has had a monumental impact on our world. Now, more than a year after the first documented cases of COVID-19, researchers are delving deeper into the preliminary data on clinical outcomes for patients and consistently finding higher infection and mortality rates in males than in females.
Men account for 73% of the COVID-19-related fatalities in China, 59% in South Korea, and 70% in Italy. The most recent data from the Centers for Disease Control and Prevention (CDC) indicate that men account for about 55% of COVID-19-related deaths in the U.S. These findings have prompted further exploration into the potential role of testosterone in COVID-19 infection and mortality.
Testosterone levels decline as men age and/or develop comorbid conditions like obesity, type II diabetes, and metabolic syndrome. Sometimes, this can lead to a condition called hypogonadism (testosterone deficiency). Previous studies have shown that low testosterone levels are associated with higher mortality rates for men in the intensive care unit (ICU) with any illness. This has held true for male ICU patients with COVID-19.
A study that looked at the clinical outcomes of 221 male patients with COVID-19 found that the men who were admitted to the ICU had much lower average testosterone levels than those who were not. Nearly half of the 46 men admitted to the ICU had serum total testosterone (TT) levels of less than 200ng/dL, and three-fourths (76%) had serum TT levels of less than 300ng/dL (a standard cut-off point for a hypogonadism diagnosis). Furthermore, of the 11 patient deaths, all had serum TT levels of less than 300ng/dL. As testosterone levels declined, ICU admission and mortality rates went up. Although one should not assume the nature of the relationship between COVID-19 and low testosterone, (meaning we cannot know if one causes the other or not,) this information is nonetheless noteworthy and deserving of further research.
Other physiological factors may be influenced by testosterone as well. For example, COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which relies on certain cellular receptors to enter cells, fuse to the cell membrane, and ultimately infect a person. Researchers believe that testosterone may enhance the cellular receptors that allow SARS-CoV-2 to enter and attach to the host cells, while the main female sex hormone (estrogen) may activate the enzymes in such a way that discourages viral entry and fusion. This is a possible explanation for why men are more susceptible to COVID-19 infection than women.
Even though testosterone may support the entry and fusion of the virus, it is protective against the dangerous inflammatory immune response that is the main cause of death from COVID-19. Testosterone helps regulate the body’s immune system and boosts the body’s anti-inflammatory response. Because hypogonadism is associated with autoimmune disease and inflammatory responses, older men with lower levels of testosterone may be more at risk for developing an overactive immune response to COVID-19. This might explain why men with lower testosterone levels have higher mortality rates than those with normal testosterone levels.
It is important to note that at this time, we cannot definitively know whether or not testosterone levels impact clinical outcomes of patients with COVID-19. Other variables such as comorbid conditions that often accompany low testosterone in older men may play a larger role in a patient’s clinical outcome than low testosterone. Therefore, further research is needed to determine if/how testosterone influences COVID-19 infection and mortality, including whether or not testosterone therapy may play a role in disease mitigation.
Resources:
Auerbach, J.M., & Khera, M. (2021). Testosterone’s Role in COVID-19. The Journal of Sexual Medicine, 18(5), 843-848. https://www.jsm.jsexmed.org/article/S1743-6095(21)00305-2/fulltext.
Centers for Disease Control and Prevention. (2021, June 9). Weekly Updates by Select Demographic and Geographic Characteristics: Provisional Death Counts for Coronavirus Disease 2019 (COVID-19). Retrieved June 15, 2021, from https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm.
