Gynecomastia is usually defined as enlargement of the male breast. This may be palpable only or may be grossly visible. Either type may be unilateral or bilateral. A small degree of palpable nonvisible gynecomastia is said to be present in about 30%-40% of clinically normal men. Most etiologies of gynecomastia can produce either unilateral or bilateral effects.

Etiologies. Major etiologies of gynecomastia are presented in the box. In most cases, estrogen (estradiol) is increased relative to testosterone, even if assay values do not demonstrate this. Considering some of the etiologies, some degree of gynecomastia is present in 20%-40% (range, 4%-70%) of boys during puberty but disappears in 1-2 years. Old age demonstrates increased incidence of gynecomastia, possibly due to testicular failure. Testicular failure, either primary (congenital or testicle damage) or secondary (pituitary FSH decrease) can induce increased pituitary production of LH, which, in turn, may induce increased Leydig cell secretion of estradiol. Obesity may result in enhanced conversion of estrogen precursors to estrogen in peripheral tissues. Adrenal hyperactivity, cirrhosis, and chronic renal failure on dialysis therapy may be associated with gynecomastia in some patients due to increased estrogen formation from circulating androgenic precursors. Ten percent to 40% of patients with hyperthyroidism may develop gynecomastia due to increase in testosterone-binding protein. Breast carcinoma in males is rare but is always a possibility in unilateral gynecomastia.

Laboratory tests. Tests most commonly ordered in patients with gynecomastia are listed in the box. These tests screen for certain possible etiologies. Elevated serum LH levels suggest testicular failure; elevated testosterone levels, Leydig cell tumor; elevated serum estradiol levels, either an estrogen-producing tumor or elevated androgen precursors that are converted to estrogens; serum hCG, testicular or certain other tumors; liver function tests, cirrhosis. There is considerable disagreement among endocrinologists regarding how many tests to order for initial screen and what tests to include in the screen. The box contains tests and procedures frequently mentioned that might be useful to nonendocrinologists. Serum prolactin is usually normal.

Selected Etiologies of Gynecomastia (% of this Category With Gynecomastia)
Physiologic etiologies
Neonatal (60%-90%)
Pubertal (adolescence) (4%-70%; 25% of overall gynecomastia cases)
Old age (40%)
Increased estrogen secretion
Testicular Leydig cell tumor (25%; 3% of overall gynecomastia cases)
hCG-secreting tumor
Adrenal cortex tumor
Increased estrogen precursors
Cirrhosis (50%)
Hyperthyroidism (10%-40%)
Recovery from severe chronic disease
Renal failure on hemodialysis (50%)
“Refeeding” gynecomastia after malnutrition (15%)
Deficiency in androgens (8% of overall gynecomastia cases)
Testicular failure (primary or secondary)
Klinefelter’s syndrome (30%-50%)
Androgen resistance syndromes
Breast carcinoma
Medication-induced etiologies (10%-20% of overall gynecomastia cases)
Testosterone inhibitors (spironolactone, cimetidine) Estrogens
Others (methyldopa, isoniazid, various psychotropic medications, cytoxins, digitalis, vitamin E
in large doses, reserpine, ketoconazole)
Idiopathic (25% of overall gynecomastia cases)

Possible Workup for Gynecomastia
Palpation of breast for tumor and examination of testis for tumor
Medication history
Inquire about chronic disease; especially dialysis for chronic renal disease, chronic liver disease, or refeeding conditions
Initial test screen
Serum estrogen (estradiol)
Serum free testosterone
Serum hCG
Serum LH
Additional tests (only if indicated)
Serum androstenedione
Urine 17-KS