5α-Reductase Inhibitors Are Associated with Reduced Risk of SARS-CoV-2 Infection: A Matched-Pair, Registry-Based Analysis

Abstract

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a disproportionately severe effect on men, suggesting that the androgen pathway plays a role in the disease. Studies on the effect of castration and androgen receptor blockade have been mixed, while 5a-reductase inhibitor (5ARI) use in men with COVID-19 (2019 novel coronavirus) have shown potential benefits. We assessed the association of 5ARI use on risk of community acquired SARS-CoV-2 infection. Materials and Methods: A total of 60,474 males in a prospective registry of people tested for SARS-CoV-2 between March 8, 2020 and February 15, 2021 were included. Using a matched cohort design, men using 5ARIs were matched 1:1 to non5ARI users. Independent analysis using unconditional multivariable logistic regression on the entire unmatched data set was completed for validation. Primary outcome measures were the association of 5ARI use on rates of SARS-Cov-2 positivity and disease severity. Results: Of the men 1,079 (1.8%) reported 5ARI use and 55,100 were available for matching. The final matched cohorts included 944 men each. Mean duration of use was 60.4 months (IQR 17e84 months). Absolute risk for infection was significantly lower in 5ARI users compared to nonusers, 42.3% (399/944) vs 47.2% (446/944), respectively (absolute risk reduction [ARR] 4.9%, OR 0.81, 95% CI 0.67e0.97, p[0.026). Unconditional multivariable logistic regression analysis of the entire study cohort of 55,100 men confirmed the protective association of 5ARI use (ARR 5.3%, OR[0.877, 95% CI 0.774e0.995, p[0.042). Use of 5ARIs was not associated with disease severity. Conclusions: Use of 5ARIs in men without prostate cancer was associated with a reduction in community acquired SARS-CoV-2 infection.

COVID-19 and androgenic status: testosterone or dihydrotestosterone have a pivotal role?

“…D-dimer level differences were only observed on day 14 and it was significantly lower in dutasteride group [20]. Absolute risk for SARS-Cov-2 infection among males treated with 5α-reductase inhibitors (mean duration of use was 60.4 months) was also significantly lower compared to control group (absolute risk reduction 4.9%; OR 0.81; 95% CI 0.67-0,97, p = 0.026) [21]. So, DHT reduction under 5α-reductase inhibitors effect can associated with lower viral entry proteins expression and, respectively, viral shedding and inflammatory markers, as well as stable T concentrations act as anticytokine protective agent.…”

5-alpha reductase inhibitors use in prostatic disease and beyond

“…Several publications have identified a protective benefit from antiandrogens in men with SARS-CoV-2. Potential benefits include lesser symptoms, reduced disease severity and fewer intensive care unit (ICU) admissions (5,6,65,66). These claims have been refuted in a recent meta-analysis, where there was no evidence for a protective benefit of androgen deprivation therapy from SARS-CoV-2 (67).…”

Anti-SARS-CoV-2 Action of 5α-Reductase Inhibitors May Be Mediated by Dehydroepiandrosterone. Letter.

“…To the Editor: We read with interest the study of Lyon et al 1 5α-Reductase inhibitor-induced testosterone and androstenedione increase may shunt these precursors to estrogens. Additional precursor steroids may be involved and more plausibly account for the observation of reduction in community-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.…”

“…To the Editor: We would like to congratulate Friedman et al on their timely study, which investigated the effect of an application limit on matching into a urology residency program. 1 In their study, applicants participating in the 2021 Match were asked to list 25 programs that they would apply to if there hypothetically were an application limit of 25, and the study team assessed match outcomes on a followup survey. Among 90 study participants who completed pre-and post-Match surveys, 13 (14%) did not match, 12 (13%) matched outside of their hypothetical list of 25 programs and 65 (72%) matched to a program on their hypothetical list.…”

“…Additional precursor steroids may be involved and more plausibly account for the observation of reduction in community-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. 1…”