Gynecomastia

Risk factors

• Obesity (aromatization of androgens to estrogens in adipose tissue)
• Aging and age-related decline in testosterone
• Chronic liver disease (impaired clearance of estrogens and SHBG changes)
• Hyperthyroidism, chronic kidney disease (especially on hemodialysis)
• Hypogonadism: Klinefelter syndrome (XXY), primary or secondary
• Tumors: testicular germ cell tumors (hCG-secreting), Leydig and Sertoli cell tumors, adrenal tumors, lung carcinoma (ectopic hCG)
• Medications: spironolactone, ketoconazole, cimetidine, finasteride, anti-androgens (bicalutamide, flutamide), estrogens, GnRH analogs, opioids, anabolic-androgenic steroids (during withdrawal), antiretrovirals (efavirenz, stavudine), some antipsychotics (risperidone), tricyclic antidepressants
• Recreational substances: alcohol, marijuana, methadone

Pathophysiology

Imbalance between stimulatory estrogen action and inhibitory androgen action on breast tissue drives ductal epithelial proliferation, periductal stromal edema, and glandular hyperplasia. The ratio shifts when estrogen rises (exogenous, tumor, peripheral aromatization), when androgens fall (hypogonadism, anti-androgens), or when binding proteins shift free hormone fractions (SHBG changes in cirrhosis or hyperthyroidism). Long-standing gynecomastia (>12 months) progresses to fibrosis and is unlikely to regress with medical therapy.

Clinical presentation

Differential diagnosis

• Pseudogynecomastia (lipomastia) — Soft, diffuse adipose tissue without a discrete subareolar mound; no symmetric concentric tissue under areola; weight loss reduces it
• Male breast cancer — Unilateral, eccentric, hard, fixed mass, often with skin retraction, nipple discharge or inversion, or axillary lymphadenopathy; mammography and biopsy
• Lipoma — Soft, mobile, non-tender mass not centered under the areola; ultrasound shows fatty tissue without glandular component
• Neurofibroma or sebaceous cyst — Superficial, well-circumscribed, may have characteristic stigmata of neurofibromatosis; not subareolar glandular
• Mastitis or breast abscess — Erythema, warmth, tenderness, fever; usually unilateral; antibiotics and drainage

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Male breast enlargement] --> B[Pinch test]
  B --> C{Firm concentric<br/>subareolar tissue?}
  C -->|No - diffuse soft fat| D[Pseudogynecomastia<br/>weight management]
  C -->|Yes - true gynecomastia| E[History + medication<br/>review + testicular exam]
  E --> F{Red flags?<br/>unilateral, hard, fixed,<br/>nipple discharge,<br/>rapid onset, testicular mass}
  F -->|Yes| G[Mammography +/-<br/>testicular US + hCG]
  F -->|No| H[Basic labs:<br/>testosterone, LH, FSH,<br/>estradiol, hCG, TSH,<br/>LFTs, creatinine, prolactin]
  H --> I{Identified cause?}
  I -->|Yes| J[Treat underlying<br/>cause / stop drug]
  I -->|No, idiopathic| K{Duration <12 mo<br/>and symptomatic?}
  K -->|Yes| L[Trial of tamoxifen]
  K -->|No - fibrotic >12 mo| M[Surgical referral<br/>if desired]

Treatment

Complications

• Persistent cosmetic deformity once fibrosis sets in (>12 months)
• Psychological distress, body image disturbance, and social withdrawal, particularly in adolescents
• Missed underlying malignancy (testicular germ cell tumor, male breast cancer, adrenal or lung tumor)
• Treatment-related: hot flashes and thromboembolism with SERMs; surgical complications including hematoma, contour irregularity, nipple necrosis, and scarring

PANCE pearls

• Distinguish true gynecomastia from pseudogynecomastia by the pinch test — slowly bring thumb and forefinger together from lateral to medial; true gynecomastia is felt as a discrete rubbery resistance, pseudogynecomastia feels uniformly soft.
• Unilateral, eccentric, hard, fixed, or skin-tethered breast lesions in men require mammography and biopsy regardless of age — male breast cancer accounts for <1% of all breast cancers but has a worse stage-matched prognosis when delayed.
• Always examine the testes — a testicular mass in a young man with new gynecomastia is a germ cell tumor until proven otherwise.
• Drug-induced gynecomastia (spironolactone, cimetidine, ketoconazole, finasteride, anabolic steroids, antiretrovirals) frequently improves within 3 months of stopping the offending agent if the tissue has not become fibrotic.
• Long-standing fibrotic gynecomastia (>1 year) is unlikely to regress with medical therapy — set expectations and refer for surgery if intervention is desired.

References

• Endocrine Society 2018 — Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline (Bhasin et al., J Clin Endocrinol Metab 2018)
• AACE 2002 — American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Evaluation and Treatment of Male Sexual Dysfunction (Petak et al., Endocr Pract 2002)
• Braunstein NEJM Review 2007 — Gynecomastia (Braunstein, NEJM 2007)
• Narula and Carlson Review 2014 — Gynaecomastia — Pathophysiology, Diagnosis and Treatment (Narula and Carlson, Nat Rev Endocrinol 2014)