Men with more severe cases of COVID-19 infection have very low levels of total testosterone, a new study finds.
Men have been dying at greater rates from COVID-19 than women, leading some to speculate that hormone differences may play a role.
“During the pandemic, there has been a prevailing notion that testosterone is bad,” Abhinav Diwan, MD, of the Washington University School of Medicine in St Louis, stated in a press release from the university. “But we found the opposite in men. If a man had low testosterone when he first came to the hospital, his risk of having severe COVID-19 — meaning his risk of requiring intensive care or dying — was much higher compared with men who had more circulating testosterone. And if testosterone levels dropped further during hospitalization, the risk increased.”
Among 90 men with COVID-19 who arrived to the Barnes Jewish Hospital in St Louis, Missouri from March to May 2020, 31 men presented with severe disease, another 35 developed severe disease 1-3 days into their hospital stay, and 24 had mild disease.
Median testosterone levels upon admission were significantly lower among men who presented with severe COVID-19 (48 ng/dL) or who developed severe COVID-19 during hospitalization (65 ng/dL) compared with men who had mild disease (151 ng/dL), the investigators reported in JAMA Network Open. Median testosterone levels were lowest at day 3 (median 19 vs 111 ng/dL) and day 7 (median 20 vs 180 ng/dL) for men with severe COVID-19 vs mild illness.
Day 3 total testosterone was 17 vs 104 ng/dL in men with and without ICU admission, 12 vs 60 ng/dL in men with and without ventilator use, and 15 vs 49 ng/dL among men who died and survived, respectively, the investigators reported.
Overall, testosterone levels in the severe COVID-19 group showed recovery at day 14 (53 ng/dL) and day 28 (102 ng/dL). All of these levels were well within the reference range for low testosterone of less than 250 ng/dL.
Men with severe COVID-19 had approximately 65% to 85% lower testosterone concentrations compared with men who had milder disease, independent of other known risk factors associated with severity of COVID-19, such as age, body mass index, comorbidities, smoking, and race, according to Dr Diwan’s team. Testosterone levels did not correlate with disease severity among the 62 women with COVID-19 who presented at the hospital.
With respect to inflammatory markers, testosterone concentrations were inversely and significantly associated with interleukin 6, C-reactive protein, interleukin 1 receptor antagonist, hepatocyte growth factor, and interferon γ–inducible protein 10 in men. Estradiol and insulin-like growth factor 1 concentrations were not associated with COVID-19 severity in men.
“These data suggest caution should be practiced with approaches that antagonize testosterone signaling or supplement estrogen to treat men with severe COVID-19,” Dr Diwan and colleagues wrote.
The investigators are now probing whether there is an association between sex hormones and cardiovascular outcomes in long-term COVID-19, when symptoms linger for many months. They may also examine whether men recovering from COVID-19 benefit from testosterone therapy.
Disclosure: Some of the study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Dhindsa S, Zhang N, McPhaul MJ, et al. Association of circulating sex hormones with inflammation and disease severity in patients with COVID-19. JAMA Netw Open. Published online May 25, 2021. doi:10.1001/jamanetworkopen.2021.11398
Evangelou Strait J. For men, low testosterone means high risk of severe COVID-19 [press release]. Washington University; May 25, 2021.