Gynecomastia: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Gynecomastia is the benign proliferation of glandular breast tissue in males, resulting from an imbalance between estrogenic and androgenic effects at the breast tissue level. It is the most common benign condition of the male breast. Clinically, gynecomastia manifests as a palpable, firm, concentric subareolar glandular disc that must be distinguished from pseudogynecomastia (adipose tissue accumulation in obese men without glandular proliferation) and breast cancer. Gynecomastia occurs in three physiological peaks: neonatal (60–90% of newborns due to transplacental estrogens), pubertal (up to 65% of adolescent males; typically regresses within 2 years), and elderly (24–65% of men over 60 due to declining testosterone and increasing adiposity-related estrogen conversion). Pathological gynecomastia — when not physiological — requires investigation to identify reversible causes, as approximately 25% have an identifiable secondary etiology. The condition causes significant psychological distress, low self-esteem, and social withdrawal in adolescents and young men.

Gynecomastia results when the ratio of biologically active estrogens to androgens at the breast tissue level increases. Causes are classified as physiological (neonatal, pubertal, senescent) or pathological. Drug-induced gynecomastia is the most common reversible cause in adults, accounting for 10–25% of cases; responsible agents include spironolactone (anti-androgenic), cimetidine, digoxin, anti-androgens (bicalutamide, flutamide — used in prostate cancer), anabolic steroids, cannabis, opioids, calcium channel blockers, and some antidepressants. Hypogonadism (primary — Klinefelter syndrome, orchitis, trauma; or secondary — hypothalamic/pituitary disease) reduces testosterone. Hyperthyroidism increases sex hormone-binding globulin, lowering free testosterone. Liver cirrhosis impairs estrogen catabolism. Chronic kidney disease on dialysis causes secondary hypogonadism. Adrenal tumors and hCG-secreting tumors (testicular, lung) elevate estrogen/hCG. Idiopathic gynecomastia accounts for ~25% after full workup.

Gynecomastia presents as unilateral or bilateral breast enlargement. The glandular tissue is palpable as a firm, rubbery, concentric disc beneath the areola — the 'button sign.' Tenderness and sensitivity are common in the acute/active phase when gynecomastia is developing (florid phase); pain typically diminishes in the chronic/fibrous phase. Unilateral eccentric or asymmetric enlargement, hard consistency, skin dimpling, nipple retraction, or nipple discharge raises concern for male breast cancer, which constitutes approximately 1% of all breast cancers. The cosmetic appearance — including visible breast mound and enlarged areola — causes body image distress, avoidance of activities requiring undressing (swimming, sport), and anxiety or depression. Klinefelter syndrome (47,XXY) may present with prominent gynecomastia alongside small testes, infertility, tall stature, and learning difficulties.

Diagnosis begins with careful history (drug and substance use history, onset, duration, symptoms of hypogonadism) and physical examination. Laboratory evaluation includes serum total and free testosterone, LH, FSH, estradiol, prolactin, hCG, AFP, TSH, liver function tests, and renal function. Elevated hCG in a male mandates imaging to exclude testicular GCT or mediastinal GCT (chest CT and scrotal ultrasound). Elevated AFP requires evaluation for hepatocellular carcinoma. Mammography or breast ultrasound is indicated for unilateral, eccentric, hard, or fixed lesions to exclude malignancy; gynecomastia shows a typical fan-shaped subareolar glandular density on mammography. MRI is rarely required. Genetic karyotyping is performed if Klinefelter syndrome is suspected. Testicular ultrasound is recommended when testicular exam is abnormal or hCG is elevated.

Withdrawal of causative drugs is the first step in drug-induced gynecomastia — spontaneous regression usually occurs within 3–6 months. Treatment of underlying conditions (hyperthyroidism, hypogonadism, cirrhosis) often leads to partial or complete regression in the florid phase. Selective estrogen receptor modulators (SERMs) — tamoxifen 10–20 mg/day or raloxifene 60 mg/day — are the most effective medical treatments, achieving >70% response rate for tender, symptomatic gynecomastia in the florid phase; they are less effective in chronic fibrous gynecomastia. Aromatase inhibitors (anastrozole, letrozole) have modest efficacy and are second-line. Androgens (danazol, testosterone) are occasionally used in hypogonadal men. Medical therapy is ineffective once fibrous transformation occurs (chronic gynecomastia >12 months). Surgical treatment — subcutaneous mastectomy (Webster technique: periareolar incision with glandular excision) ± liposuction — is the definitive treatment for persistent, symptomatic, or cosmetically significant gynecomastia not responding to medical management. Simon grade III (skin excess) requires skin excision with nipple repositioning.

Gynecomastia is a benign condition with an excellent prognosis. Physiological gynecomastia — neonatal, pubertal, and senescent — resolves spontaneously in 75–90% of affected individuals without treatment, typically within 1–2 years of onset. Drug-induced gynecomastia regresses in most patients within 3–6 months of withdrawing the causative agent. Pathological gynecomastia resolves or significantly improves when the underlying cause (hyperthyroidism, hypogonadism, liver disease) is successfully treated, provided the condition has not progressed to the fibrotic chronic phase. Medical treatment with SERMs (tamoxifen, raloxifene) achieves volume reduction in over 70% of patients in the florid phase. Chronic gynecomastia (>12 months duration) has undergone fibrous transformation and is unlikely to respond to medical therapy — surgical subcutaneous mastectomy is definitive, with >95% patient satisfaction rates and very low recurrence risk. The psychological burden of gynecomastia can be substantial, particularly in adolescents — resolution of the physical deformity, whether spontaneous or surgical, generally leads to significant improvement in body image, self-esteem, and quality of life. Male breast cancer must be excluded in all presentations — when excluded, life expectancy is not affected by gynecomastia itself. Long-term monitoring is required only in cases where an underlying endocrine disorder necessitates ongoing surveillance.

Drug-induced gynecomastia can be partially prevented by choosing alternative medications when available — using eplerenone instead of spironolactone in males with hyperaldosteronism, or carefully monitoring for gynecomastia in men initiated on anti-androgen therapy for prostate cancer. Prophylactic breast irradiation (one fraction of 12 Gy) administered before anti-androgen initiation prevents or reduces gynecomastia in prostate cancer patients. Avoidance of anabolic steroids, cannabis, and high-dose exogenous estrogens eliminates these iatrogenic causes. Weight management reduces adiposity-related peripheral aromatization of androgens to estrogens in older men. Early treatment of pubertal gynecomastia with tamoxifen may accelerate resolution and reduce the proportion of patients requiring surgery.

Prompt evaluation is needed for: unilateral breast mass that is hard, eccentric, or fixed; nipple discharge (especially bloody); skin changes (dimpling, erythema, ulceration); axillary lymphadenopathy; or rapid growth of breast tissue — all of which raise concern for male breast cancer and require urgent breast surgery referral. Any male with gynecomastia and markedly elevated serum hCG requires immediate evaluation for testicular GCT. Adolescents with gynecomastia persisting beyond 2 years without sign of regression, or causing significant psychosocial distress, should be referred to a pediatric endocrinologist. Adult males with symptomatic bilateral gynecomastia and no obvious cause warrant endocrinological evaluation to identify hypogonadism, liver disease, hyperthyroidism, or a secreting tumor.