Testosterone Replacement Therapy and Risk of COVID-19 and Effect of COVID-19 on Testosterone's Treatment Effect.

Context: Whether circulating testosterone, dihydrotestosterone, and estradiol levels or testosterone replacement therapy (TRT) affects the risk of COVID-19 and whether COVID-19 affects response to TRT remains unknown.

Objective: The study evaluated whether baseline testosterone, dihydrotestosterone, and estradiol levels or TRT are associated with risk of developing COVID-19 and whether COVID-19 affects treatment response to TRT.

Methods: Among 5204 men, aged 45 to 80 years, with hypogonadism in the TRAVERSE trial, 379 developed COVID-19. We compared baseline and on-treatment hormone levels, and safety and efficacy in participants with and without COVID-19 diagnosis.

Results: Neither baseline nor on-treatment testosterone, estradiol, and dihydrotestosterone levels prior to COVID-19 differed significantly between men with and without COVID-19 diagnosis. Incidence of COVID-19 was similar in participants randomized to TRT or placebo groups (3-year Kaplan-Meier incidence 8.0% in TRT and 8.6% in placebo group, P = .823). Incidences of COVID-19-related hospitalizations (38.5% vs 32.8%, P = .222) and deaths (12.8% vs 8.9%, P = .247) were similar in the TRT and placebo groups. Changes in hypogonadal symptoms, libido, energy, and hemoglobin/hematocrit in response to TRT were attenuated in testosterone-treated men who developed COVID-19. Incidences of major adverse cardiovascular events, venous thromboembolism, and acute kidney injury were similar in those with COVID-19 diagnosis and those without.

Conclusion: In men with hypogonadism and cardiovascular disease (CVD) or increased risk of CVD, baseline and pre-COVID-19 on-treatment testosterone, dihydrotestosterone, and estradiol levels were similar in those who developed COVID-19 and those who did not. TRT did not affect the risk of COVID-19. COVID-19 attenuated the treatment response to TRT.