Testosterone Deficiency

Male testosterone deficiency, or hypogonadism, is diagnosed clinically and biochemically. The patient must have symptoms or signs that fit androgen deficiency and unequivocally low testosterone confirmed on repeat testing. Fatigue with one low afternoon result is not enough. The hypothalamic-pituitary-testicular axis explains the laboratory pattern. Pulsatile gonadotropin-releasing hormone from the hypothalamus stimulates pituitary LH and FSH. LH acts on Leydig cells to support testosterone production; FSH supports Sertoli-cell function and spermatogenesis. Testosterone and estradiol then provide negative feedback to the hypothalamus and pituitary. - Primary hypogonadism is testicular failure: testosterone is low, so LH and FSH rise as the pituitary tries to stimulate the testes. - Secondary hypogonadism is hypothalamic or pituitary dysfunction: testosterone is low, but LH and FSH are low or inappropriately normal. A “normal” LH is abnormal when testosterone is clearly low because it should be elevated in response. Most circulating testosterone is protein-bound. A small free fraction is biologically available, and the balance changes when sex hormone-binding globulin (SHBG) changes. Obesity, type 2 diabetes, hypothyroidism, glucocorticoid use, liver disease, HIV, nephrotic syndrome, and aging can alter...