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Study Examines Link between Hormones and Sex Disparity in COVID-19 Incidence and Severity

June 28, 2022

The incidence and severity of COVID-19 have been linked with multiple factors, including age, comorbid conditions, and gender. Although men and women manifest a similar incidence of COVID-19, men have a greater risk of more severe illness. Explanations for sex differences in outcomes include differences in health behaviors (e.g., smoking history), incidence of comorbidities (e.g., lung and cardiovascular disease), genetics, and biology, including variations in sex hormones.  A recent study led by Kyung Min Lee, PhD, of HSR&D’s VA Informatics and Computing Infrastructure (VINCI), evaluated the hypothesis that men treated with androgen-deprivation therapy (ADT)—a hormone therapy for prostate cancer—have lower incidence and severity of COVID-19.

Using VA data, including VA’s COVID-19 Shared Data Resource (CSDR), investigators identified 246,087 male VA patients who had been tested for COVID in the VA healthcare system from February 15 to July 15, 2020. The study’s primary comparison for both incidence and severity was patients with ADT exposure (n=3,057) vs. patients with non-prostate cancer who had no ADT exposure (n=39,096). After correcting for baseline characteristics, such as smoking and other comorbidities and the likelihood of undergoing COVID testing, findings showed that ADT was associated with reduced incidence and severity of COVID-19 among male Veterans. Androgens have an immunosuppressive action by reducing T cell function and interferon responses. Androgen effects on COVID-19 are complex, however, since abnormally low circulating levels of testosterone during the later phase of COVID infection has been associated with poor outcome. Nevertheless, these results suggest that testosterone and androgen-receptor signaling may confer increased risk for infection and contribute to severe COVID-19 pathophysiology in men.

Lee KM, Heberer K, Gao A, et al. A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19. Frontiers in Medicine. May 4, 2022; online ahead of print.

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