BASICS
Description
- Benign glandular proliferation of male breast tissue.
- Due to increased estrogen activity relative to androgen.
- Transient in neonates and adolescents; persistent or adult-onset usually pathologic.
- Differentiate from pseudogynecomastia (lipomastia).
Epidemiology
- 60-90% of infants, 50-60% of pubertal males have transient gynecomastia.
- 36-57% prevalence in adult males.
- Bulgarian study: 3.9% incidence in Caucasian boys aged 10–19.
Etiology and Pathophysiology
- Altered estrogen:androgen ratio from:
- Decreased androgen production.
- Increased estrogen production.
- Increased peripheral conversion of androgens to estrogens.
- Inhibition of androgen receptor.
- Increased sex hormone-binding globulin (SHBG) reducing free testosterone.
- Displacement of estrogens from SHBG by drugs.
Risk Factors
- Physiologic: neonatal, pubertal.
- Pathologic: idiopathic (25%), age-related decline in testosterone, increased aromatase activity in adipose tissue.
- Illicit drugs: marijuana, heroin, methadone, alcohol, amphetamines.
- Hormones: androgens, anabolic steroids, estrogens, hCG.
- Antiandrogens: bicalutamide, flutamide, nilutamide, cyproterone, GnRH agonists.
- Medications: metronidazole, ketoconazole, minocycline, isoniazid, cimetidine, ranitidine, metoclopramide, PPIs, methotrexate, digoxin, spironolactone, calcium channel blockers, ACE inhibitors, amiodarone, antidepressants, antipsychotics, HIV meds.
- Other causes: primary hypogonadism (Klinefelter syndrome), testicular tumors, adrenal tumors, ectopic hCG tumors, cirrhosis, hyperthyroidism, renal disease, malnutrition.
Commonly Associated Conditions
- Prostate carcinoma (due to treatment).
- Primary hypogonadism.
- Testicular tumors (Leydig, Sertoli cell tumors).
- Klinefelter syndrome.
- Cirrhosis.
DIAGNOSIS
History
- Assess symptoms of hypogonadism: erectile dysfunction, decreased libido, muscle mass.
- Review family history: Carney complex, Peutz-Jeghers syndrome.
- Detailed medication and substance use history including illicit drugs and herbal supplements.
Physical Exam
- Palpate glandular tissue (>1 cm diagnostic).
- Simon’s classification for severity:
- Grade I: small enlargement, no skin redundancy.
- Grade IIa: moderate enlargement without redundancy.
- Grade IIb: moderate with redundancy.
- Grade III: marked enlargement with redundancy.
- Usually bilateral but may be unilateral.
- Breast discharge uncommon and concerning.
- Examine thyroid, abdomen, genitals.
- Visual field exam to assess pituitary involvement.
Differential Diagnosis
- Pseudogynecomastia (fat deposition).
- Breast cancer (eccentric mass, skin changes).
- Lipomas, sebaceous cysts, hematoma, mastitis.
Diagnostic Tests
- LH (elevated in primary hypogonadism).
- Morning total and free testosterone.
- hCG (germ cell tumors).
- Estradiol (Leydig, Sertoli, adrenal tumors).
- DHEA-S (adrenal tumors).
- Prolactin (pituitary tumors).
- Urine drug screen.
- Additional: creatinine, LFTs, TFTs as needed.
- Imaging: testicular ultrasound if tumor suspected.
- Biopsy if malignancy suspected.
TREATMENT
General Measures
- Neonatal and pubertal gynecomastia usually resolves within 6-24 months.
- Stop offending drugs and treat underlying conditions.
Medications
- No FDA-approved drugs specifically.
- Selective estrogen receptor modulators (SERMs): Tamoxifen 10–20 mg/day; raloxifene 60 mg/day show benefit.
- Aromatase inhibitors: anastrozole used in prostate cancer patients.
Additional Therapies
- Prophylactic radiotherapy in prostate cancer patients undergoing androgen deprivation.
Surgery
- Indicated if persistent >12 months, severe symptoms, cosmetic concerns, or suspicious biopsy.
- Multiple surgical techniques available with good satisfaction.
ONGOING CARE
Follow-up
- Monitor every 3–6 months for 24 months.
- Medical therapy if severe symptoms persist 6–12 months.
- Surgery if symptoms persist 12–24 months.
- Routine yearly breast exams if mild or asymptomatic.
Patient Education
- Reassure benign nature in most cases.
- Counsel on drug avoidance and underlying disease management.
Prognosis
- Good in physiologic cases (spontaneous regression).
- Improvement with treatment or removal of offending agents.
- Surgery results in high patient satisfaction.
Clinical Pearls
- Transient gynecomastia common in neonates and adolescents.
- Adult persistent gynecomastia usually pathologic.
- Consider hormonal and tumor causes in adult onset.
- SERMs and aromatase inhibitors show promise but surgery remains mainstay for refractory cases.
References
- Kanakis GA, Nordkap L, Bang AK, et al. EAA clinical practice guidelines-gynecomastia evaluation and management. Andrology. 2019;7(6):778-793.
- Burger A, Sattler A, Grünherz L, et al. Scar versus shape: patient-reported outcome after different surgical approaches to gynecomastia measured by modified BREAST Q®. J Plast Surg Hand Surg. 2023;57(1-6):1-6.