key: cord-0686542-gvt0t80x
authors: MacDonald, Scott; Wambier, Carlos Gustavo
title: Letter to the Editor on “COVID-19 Infection in Men on Testosterone Replacement Therapy”
date: 2021-03-19
journal: J Sex Med
DOI: 10.1016/j.jsxm.2021.03.003
sha: 22cba809c7472e98388cf47d74fd7cd927acd8f1
doc_id: 686542
cord_uid: gvt0t80x

nan

To the Editors, Rambhatla et al recently investigated whether testosterone replacement therapy (TRT) is associated with worse COVID-19 clinical outcomes. 1 The authors performed a retrospective study and identified 32 men undergoing TRT and matched them with 63 other men not on TRT. They concluded that TRT is not associated with worse clinical outcomes in men diagnosed with COVID-19. 1 We do not agree with this conclusion, and suspect that the opposite is true based on the data reported in the article. The cohort of men undergoing TRT showed an extremely high hospitalization (62.5%) and fatality rate (9.4%). 1 These rates are significantly higher than the hospitalization and death rates reported by the CDC for men in a similar age group in the United States.

The authors used the Greedy Nearest Neighbor method to select for matched controls based on age, race, body mass index, and ZIP code. We respectfully request to see data for the entire population of men, as well as an analysis that compares clinical outcomes for the population of men undergoing TRT to the total population of men not on TRT within the same age group.

Based on recent studies that demonstrate benefits of antiandrogen therapy in men diagnosed with COVID-19, we hypothesize that androgen therapy does not have a neutral impact on COVID-19 disease severity, but rather contributes to more severe COVID-19 symptoms. [2] [3] [4] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and subsequent infection is mediated by the transmembrane protease, serine 2 (TMPRSS2), which is promoted by the androgen receptor. 5 Further, men infected with SARS-CoV-2 are more than twice as likely to be admitted to the ICU than women infected with SARS-CoV-2. 6 As such, it is plausible to hypothesize that androgens play an important role in COVID-19 severity, while estrogen and progesterone may play a protective role. 7 Dutasteride is a 5-alpha-reductase inhibitor (5ARi) that works by blocking the conversion of testosterone to dihydrotestosterone (DHT), a more potent androgen. A retrospective study showed a reduction of COVID-19 symptoms in males with androgenic alopecia (AGA) who were taking dutasteride at the time of COVID-19 diagnosis compared to males with AGA who were not taking a 5ARi. 2 In addition, the results from a randomized, placebo-controlled clinical trial (RCT) suggest that early therapy with dutasteride reduces viral shedding time and inflammatory markers in males infected with SARS-CoV-2 compared to males treated with a placebo. 3 Similarly, the results from a RCT utilizing proxalutamide, a very potent anti-androgen, were associated with a marked reduction of COVID-19 symptoms and hospitalization rates in men. 8 When proxalutamide was used to treat both males and females diagnosed with mild-tomoderate COVID-19 enrolled in a RCT, it displayed improvement in multiple biochemical markers for disease severity, including viral shedding time. 9 Lastly, a recent case study demonstrated that administration of proxalutamide markedly improved symptoms and laboratory markers of COVID-19 disease severity in 24 hours in an otherwise healthy 28 yearold male patient who had been taking the androgenic anabolic steroid oxandrolone. 4 These studies suggest the potential for increased COVID-19 severity in men diagnosed with COVID-19 undergoing TRT. As such, we disagree with the conclusion presented in the article, and hypothesize that androgen therapy is likely associated with worse clinical outcomes in men diagnosed with COVID-19.

COVID-19 Infection in Men on Testosterone Replacement Therapy

5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia

Early Antiandrogen Therapy With Dutasteride Reduces Viral Shedding, Inflammatory Responses, and Time-to-Remission in Males With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Interventional Trial (EAT-DUTA AndroCoV Trial -Biochemical). Cureus

Potential risk for developing severe COVID-19 disease among anabolic steroid users

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

The impact of sex and gender on immunotherapy outcomes

Mortality in COVID-19 amongst women on Hormone Replacement Therapy or Combined Oral Contraception: A cohort study. medRxiv

Applied Biology I. Results of NCT04446429

Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial