Los Angeles—Some retrospective analyses last year held out the promise that using drugs that suppress the androgen receptor might help reduce the incidence and severity of COVID-19 in men.

That led to the Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase II, placebo-controlled, double-blind, randomized clinical trial. Researchers from the Veterans Affairs Greater Los Angeles Healthcare System and the University of California Los Angeles compared the efficacy of degarelix plus standard care versus placebo plus standard care on clinical outcomes in 96 men hospitalized with COVID-19 but not requiring invasive mechanical ventilation.

Degarelix is approved by the FDA for prostate cancer therapy. With an immediate onset of action, the drug binds to the gonadotropin-releasing hormone receptors in the pituitary gland and rapidly suppresses luteinizing and follicle-stimulating hormone secretion. That decreases testosterone production within the testes and rapidly reduces circulating androgen levels, according to the study.

The authors explained that the trial was undertaken because SARS-CoV-2 entry requires the TMPRSS2 cell surface protease, and antiandrogen therapies reduce expression of TMPRSS2. The question was whether temporary androgen suppression induced by degarelix improved the clinical outcomes of COVID-19 inpatients.

In results published in the Journal of the American Medical Association Network Open, researchers reported that their randomized clinical trial, which included 96 men, was stopped for futility. Androgen suppression with the addition of degarelix versus placebo plus standard care did not result in lower rates of mortality, ongoing hospitalization, or requirement for mechanical ventilation—all part of the composite endpoint.

"In this randomized clinical trial of androgen suppression vs. placebo and usual care for men hospitalized with COVID-19, degarelix did not result in amelioration of COVID-19 severity," the study concluded.

The authors suggested the following reasons the trial did not go as anticipated:

• First, suppression of testosterone is itself a physiologic response to acute, critical illness. In the HITCH study, total testosterone decreased in both treatment groups, though markedly more so in the degarelix group.

• Second, the timing of downregulation of TMPRSS2 may have limited the effect of androgen-deprivation therapy on the severity of illness. At enrollment, patients might no longer have been dependent on ongoing viral infection but rather on a hyperactivated immune response that results in end-organ damage.

• Third, because androgens are immunosuppressive, they might have inhibited innate and adaptive immunity, including T-cells.

• Fourth, in men, serum estrogen is derived from testosterone, so testosterone suppression should result in lower absolute concentrations of serum estrogen, which has been reported to suppress the expression of viral coreceptors. "In the context of medical castration, reduced estrogen concentrations could counterbalance the effects of reduced testosterone on viral coreceptor expression," the authors wrote.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.