Testosterone

Testosterone is the principal androgen, produced mainly by Leydig cells in the testes in men and in smaller amounts by the ovaries and adrenals in women. It supports muscle mass, bone density, libido, mood, and erythropoiesis. Laboratories report total testosterone alongside free or bioavailable testosterone, since roughly 98% circulates bound to SHBG and albumin. Levels typically decline with age in men; lower values are observationally associated with sarcopenia, frailty, metabolic syndrome, and higher all-cause mortality and adverse cardiometabolic outcomes, with confounding by obesity, inflammation, and SHBG changes. The TRAVERSE trial (Lincoff et al. 2023 NEJM) found cardiovascular non-inferiority for testosterone therapy in hypogonadal men, with elevated atrial-fibrillation and pulmonary-embolism signals, informing the FDA's 2025 label update that removed the boxed cardiovascular warning while retaining cautions on atrial fibrillation, pulmonary embolism, and blood-pressure elevation.