Gynaecomastia

Gynaecomastia is benign enlargement of male breast glandular tissue, caused by an imbalance between oestrogen and androgen action at the breast. It differs from pseudogynaecomastia (fat only) and from breast cancer.

It is common: about 60% of adolescent boys, 25% of adult men and up to 70% of men aged 50 to 80 years have palpable tissue. Physiological forms occur in neonates, at puberty and in older age.

Drugs cause about 10 to 25% of cases (spironolactone, finasteride and dutasteride, bicalutamide and other antiandrogens, androgens and anabolic steroids, gonadotrophin releasing hormone analogues, ketoconazole, cimetidine, risperidone, digoxin, efavirenz, cannabis and alcohol). Others are hypogonadism, cirrhosis, hyperthyroidism, renal failure and tumours.

Pathophysiology.

A rise in the oestradiol to testosterone ratio (more oestrogen, less androgen, or less androgen receptor action) stimulates ductal proliferation and stromal growth.

Tumours secreting human chorionic gonadotrophin or oestrogen (testicular, adrenal) drive aromatase activity. Klinefelter syndrome raises breast cancer risk many fold.

• Tender, firm subareolar glandular tissue, symmetrical or unilateral, concentric around the nipple. Pain is common in recent onset.
• Look for testicular size, masses, signs of hypogonadism, liver disease and thyroid disease.

Red flags.

• Hard, fixed, eccentric lump, skin dimpling, nipple retraction or bloody discharge, axillary nodes (breast cancer).
• Testicular mass or rapid growth with feminisation (tumour).

• History of drugs, alcohol and substance use, and examination of breasts, testes and abdomen.
• Tests when the cause is not clear: testosterone, LH, FSH, oestradiol, prolactin, beta human chorionic gonadotrophin, thyroid stimulating hormone, liver and kidney function.
• Testicular ultrasound for any mass or raised beta human chorionic gonadotrophin or oestradiol. Chest and adrenal imaging for raised dehydroepiandrosterone sulphate or oestradiol.
• Breast ultrasound or mammography and biopsy for suspicious findings.
• No investigation is needed in an asymptomatic adolescent with typical pubertal gynaecomastia and a normal examination.

Differential diagnosis.

• Pseudogynaecomastia (obesity), lipoma and breast cancer.
• Hypogonadism (primary and secondary), Klinefelter syndrome and androgen insensitivity syndrome.
• Hyperthyroidism, cirrhosis, renal failure, refeeding and tumours.

• Stop or replace the causative drug where possible. Treat the underlying disorder (testosterone for hypogonadism, thyroid and liver disease care, tumour resection).
• Pubertal gynaecomastia: reassure and observe for 1 to 2 years, since most settles.
• Painful, recent onset (under 12 months) gynaecomastia: tamoxifen 10 to 20 mg daily for 3 to 6 months (off label); aromatase inhibitors are less effective.
• Persistent (over 12 months) fibrotic tissue or severe distress: surgery (liposuction or mastectomy).
• Prevention in men starting bicalutamide or other antiandrogens: prophylactic breast radiotherapy or tamoxifen 20 mg daily.
• Breast cancer: refer to a breast cancer team for assessment and treatment.

Special groups. Adolescents: psychological support and monitoring for breast related distress.

Monitoring. Review at 3 to 6 months for response, and at 12 months to decide on surgery.

Referral and escalation. Endocrinology for unexplained or persistent gynaecomastia; breast surgery for suspicious masses or surgical treatment; urology for testicular mass.