Given the rapid spread of the coronavirus disease 2019 (COVID-19) pandemic and its overwhelming effect on health care systems and the global economy, innovative therapeutic strategies are urgently needed. The proposed primary culprit of COVID-19 is the intense inflammatory responsedan augmented immune response and cytokine stormdseverely damaging the lung tissue and rendering some patients' conditions severe enough to require assisted ventilation. Sex differences in the response to inflammation have been documented and can be attributed, at least in part, to sex steroid hormones. Moreover, age-associated decreases in sex steroid hormones, namely, estrogen and testosterone, may mediate proinflammatory increases in older adults that could increase their risk of COVID-19 adverse outcomes. Sex hormones can mitigate the inflammation response and might provide promising therapeutic potential for patients with COVID-19. In this article, we explore the possible antiinflammatory effects of estrogen and testosterone and the anabolic effect of testosterone, with particular attention to the potential therapeutic role of hormone replacement therapy in older men and women with COVID-19.

K.F.H. reports being an investigator on grants to Brigham and Women's Hospital from Eli Lilly and Company and GlaxoSmithKline for unrelated studies. B.T.B. reports being an investigator on grants to Brigham and Women's Hospital from Eli Lilly and Company, Baxalta, GlaxoSmithKline, and Pacira Pharmaceutical Inc for unrelated studies; received personal fees from Aetion Inc and from the Alosa Foundation outside the submitted work; and served on an expert panel for a postpartum hemorrhage quality improvement project that was conducted by the Association of Women's Health, Obstetric, and Neonatal Nurses and funded by a grant from Merck for Mothers. S.H.-D. reports being an investigator on grants to her institution from Eli Lilly and Company and GlaxoSmithKline for unrelated studies; receiving personal fees from UCB outside the submitted work; and having served as an epidemiologist with the North American Antiepileptic Drug Pregnancy Registry, which is funded by multiple companies.

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