Testosterone in COVID-19 - Foe, Friend or Fatal Victim?

The evidence derived from observational studies suggests male gender, diabetes and central obesity to be risk factors associated with an increased COVID-19-related case fatality. The precise pathophysiology behind this gender difference in mortality outcomes remains unclear at this stage, although it is worth exploring a possible role of testosterone as one of the contributory factors. The observed role of androgens in transcription of transmembrane protease serine-2, which facilitates COVID-19 anchoring to angiotensin-converting enzyme 2 cell surface receptors, seems to suggest that higher testosterone levels might be detrimental for outcomes. On the other hand, men with type 2 diabetes mellitus and central obesity have an increased prevalence of hypogonadotropic hypogonadism, with inhibition of gonadotropin-releasing hormone secretion induced by inflammatory cytokines being one of the postulated mechanisms. The increased COVID-19 case fatality in this cohort might perhaps reflect an underlying pro-inflammatory state, with low testosterone levels being either a surrogate marker of a poor metabolic state or playing a more active role in propagation of inflammation and thrombosis.