The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: “testosterone”, “androgens”, “inflammatory cytokines”, “inflammatory biomarkers” with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti–tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn’s disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by mechanisms inhibiting inflammatory cytokine expression and function. Mechanistically, androgens regulate the expression and function of inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CRP (C-reactive protein). Here, we suggest that testosterone regulates multiple and overlapping cellular and molecular pathways involving a host of immune cells and biochemical factors that converge to contribute to attenuation of the inflammatory process.

Post-orgasmic illness syndrome (POIS) is an uncommon condition in which men experience debilitating symptoms following orgasm, including anxiety, weakness, and lassitude. The etiology is unknown, and treatment challenging. We present a 25y man with POIS since puberty. He dreaded ejaculation due to his subsequent symptoms. Multiple prior treatments had failed. Blood tests revealed testosterone (T) deficiency. hCG was prescribed. At 6 weeks T levels normalized with near-complete resolution of symptoms. This successful result argues for hormonal investigation in men with POIS, and a trial of hCG or T therapy if total or free T is low or borderline.

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