Asymptomatic gynecomastia is common enough that it could almost be considered a normal condition, with a trimodal age distribution.
Gynecomastia is classified into 3 major groups: physiological, pathological, and idiopathic.
- Due to elevated estrogen concentrations in fetal blood
- Typically regresses by the age of 3 weeks
- Occurs in 60%–90% of neonates
- Adolescent boys
- Due to a transient increase in estradiol concentration at the onset of puberty
- Typically regresses after 18 months of puberty
- Occurs in 50% of male teenagers
- Not common after the age of 17 years
- Older men
- Due to increased body fat content, which is responsible for the increased conversion of androgens to estrogens
- Occurs in up to 70% of men aged 50–69 years
- Medications: estimated to cause approximately 10%–25% of all cases of gynecomastia
- Definitely associated with gynecomastia: estrogens, cimetidine, ketoconazole, growth hormone, gonadotropins, antiandrogen therapies, and 5-alpha-reductase inhibitors
- Probably associated with gynecomastia: first-generation and atypical antipsychotics in adults, calcium channel blockers, omeprazole, HIV drugs, alkylating agents, anabolic steroids, alcohol, and opioids
- Many other medications have been reported to be associated with gynecomastia but good evidence is lacking.
- Metabolic disorders: liver disease, cirrhosis, type 1 diabetes, hyperthyroidism, chronic renal disease
- Hypogonadism: Klinefelter syndrome
- Testicular tumors: germ cell, Leydig cell, Sertoli cell, sex cord
- Adrenal tumors: adenoma or carcinoma
- Cannot be linked to a specific etiology
- 25% of cases of gynecomastia are idiopathic.
To recall the causes of gynecomastia, remember CODES:
- C: Cirrhosis
- O: Obesity
- D: Digoxin
- E: Estrogen
- S: Spironolactone
- Most patients are asymptomatic.
- Clinical features:
- Concentric with the nipple, usually bilateral and firm
- Can present with tender areolar complex
- Clinical history:
- Family history of gynecomastia
- Age of onset and duration of the condition
- History of mumps (if affected by mumps orchitis, with subsequent impairment in the production of testosterone by Leydig cells), testicular trauma, alcohol use, drug use
- Any recent changes in nipple size and any pain or discharge from the nipples
- History of sexual dysfunction, infertility, or hypogonadism
- Consider malignancy if:
- Unilateral, ulcerative, fixed, hard, not concentric with nipple
- Associated with bloody discharge or axillary lymphadenopathy
- Diagnosis is made via relevant history and physical examination:
- History: age, family history, drug use (e.g., performance-enhancing drugs in athletes), medication use, growth rate
- Physical exam: palpable, concentric, symmetrical, firm, or rubbery disks of tissue at least 0.5 cm in diameter; usually located directly beneath the areolar area
- Serum levels of testosterone, estradiol, luteinizing hormone, and human chorionic gonadotropin (hCG) → to help identify pathological causes
- Luteinizing hormone and follicle-stimulating hormone (FSH) levels → to exclude hypogonadism
- Liver function tests, renal function tests, and thyroid hormone assay → to identify reversible or treatable causes of gynecomastia
- Biopsy: if suspicious for malignancy
- Histology of gynecomastia: extensive ductal epithelial hyperplasia in the early stages, rarely with lobular proliferation; later stages show fibrosis
- Mammography and breast ultrasonography with biopsy: in case of suspicion of breast cancer
- Testicular ultrasound: may be indicated to exclude testicular tumors
- Abdominal computed tomography (CT) scans or ultrasonography: to exclude liver tumors and/or liver cirrhosis
- Treatment of underlying cause:
- Discontinue the offending drug
- Treat the underlying medical condition
- Indicated in physiological gynecomastia throughout age period
- Indicated in pathological gynecomastia < 6 months of onset
- Mammography and biopsy if clinical suspicion of malignancy
- Medical therapy:
- Testosterone replacement: in patients with hypogonadism
- Selective estrogen receptor modulators (e.g., tamoxifen): for severe physiological gynecomastia or idiopathic gynecomastia lasting longer than 3 months
- Surgery: Subcutaneous mastectomy is indicated for cosmesis in gynecomastia lasting longer than 1 year.
The following conditions are differential diagnoses for gynecomastia:
- Hypogonadism: a condition characterized by decreased sex steroid production in the gonads. In men, this can be the result of primary or secondary testicular failure due to pituitary or hypothalamic disorders.
- Breast cancer: a malignancy that originates in breast tissue; 1% of breast cancer cases occur in men. This diagnosis should be considered if the mass is unilateral, hard, fixed, associated with skin dimpling, ulcerative, not concentric with the nipple, or associated with bloody discharge, or if axillary lymphadenopathy is present.
- Mastitis: inflammation of the mammary gland tissue, which can be lactational or non-lactational. Mostly affects women of childbearing age within the first 6 weeks of lactation.
- Lipoma: a benign soft tissue tumor that is composed of mature adipocytes. Lipoma usually presents as a subcutaneous, soft mass that is mobile and painless.
- Pseudogynecomastia: when the male breast area has excess adipose (fat) tissue behind, around, and under the nipples. The condition is usually due to obesity.
- Johnson, R. E., & Murad, M. H. (2009). Gynecomastia: pathophysiology, evaluation, and management. Mayo Clinic proceedings, 84(11), 1010–1015. https://doi.org/10.1016/S0025-6196(11)60671-X
- Braunstein GD, Anawalt BD. Clinical features, diagnosis, and evaluation of gynecomastia in adults. UpToDate Evidence-Based Medicine. Retrieved on August 28, 2020, from https://www.uptodate.com/contents/clinical-features-diagnosis-and-evaluation-of-gynecomastia-in-adults
- Hoda SA, Brogi E, Koerner FC, Rosen PP. Rosen’s Breast Pathology, 4th Edition. Lippincott Williams & Wilkins.
- Nuttall, F. Q., Warrier, R. S., & Gannon, M. C. (2015). Gynecomastia and drugs: a critical evaluation of the literature. European journal of clinical pharmacology, 71(5), 569–578. https://doi.org/10.1007/s00228-015-1835-x
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