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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

  1. Kanakis GA, Nordkap L, Bang AK, et al. EAA clinical practice guidelines-gynecomastia evaluation and management. Andrology. 2019;7(6):778-793.
  2. 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.