Pathophysiology
Clinical meaning
Male hypogonadism involves insufficient testosterone production, classified as primary (testicular failure โ elevated LH/FSH with low testosterone) or secondary/central (hypothalamic-pituitary dysfunction โ low/normal LH/FSH with low testosterone). The hypothalamic-pituitary-gonadal (HPG) axis: GnRH from the hypothalamus (pulsatile secretion) stimulates pituitary LH (stimulates Leydig cell testosterone production) and FSH (stimulates Sertoli cell spermatogenesis). Testosterone (T) exerts negative feedback at both hypothalamus and pituitary. In the periphery, T is converted to dihydrotestosterone (DHT) by 5-alpha-reductase (DHT mediates prostate growth, male pattern hair, sebaceous activity) and to estradiol by aromatase (E2 mediates bone health, fat distribution, and also provides negative HPG feedback). Free testosterone (2-3% of total) is the biologically active fraction; the rest is bound to SHBG (60-70%) and albumin (30-40%). Conditions that increase SHBG (aging, liver disease, hyperthyroidism) can lower free T while total T appears normal. Primary causes include Klinefelter syndrome (47,XXY), testicular trauma, orchitis, and chemotherapy/radiation. Secondary causes include obesity (most common acquired cause โ adipose aromatase converts T to E2, which suppresses GnRH), opioids, pituitary tumors, and hyperprolactinemia.