Gynecomastia

Definition

• Hypertophy of male breast tissue

Etiology

• Involves an imbalance of bioavailable estrogen and testosterone causing hypertrophy of the ductal tissue

Pathophysiology

• In newborns: maternal estrogen exposure
• In pubescent males: estrogen synthesis increases more quickly than testosterone
• In elderly males: multifactorial including low testosterone, increased sex hormone binding globumin (SHBG), and obesity causing increased peripheral aromatization
• Other mechanisms include
  • Decreased testosterone, as in primary or secondary hypogonadism
  • Increased estrogens, as in liver failure and obesity and certain medications/supplements
  • Increased SHBG, which decreases bioavailable testosterone more than estrogen

Differential Diagnosis

• Pseudogynecomastia (increased subcutaneous fat)
• Primary hypogonadism (low T, high LH)
  • Mumps orchitis
  • Hemochronatosis
  • Klinefelter syndrome
  • Chemotherapy
  • Radiation therapy
  • Trauma
• Secondary hypogonadism (low T, low LH)
  • Prolactinoma
  • Hemochromatosis
  • Kallman syndrome
  • Radiation therapy
  • Pituitary masses
    • Craniopharyngioma
• Change in sex-hormone binding globulin (SHBG)
  • Hyperthyroidism
  • Chronic liver disease
  • Chronic kidney disease?
• Malignancy
  • Leydig/Sertoli tumours
  • Adrenal neoplasm
  • Germ-cell tumour, gonadal or non-gonadal
• Medications
• Natural health products
  • Soy
  • Flax
  • Tea tree oil
  • Lavender oil

Drugs

Class	Examples
Hormones	Androgens, anabolic steroids, estrogens, estrogen agonists, and hCG
Antiandrogens	Bicalutamide, flutamide, nilutamide, cyproterone, and GRH agonists
Antibiotics	Metronidazole, ketoconazole, minocycline, isoniazid
Antiulcer meds	Cimetidine, ranitidine, omeprazole
Chemo	Methotrexate, alkylating agents, vinca alkaloids
Cardiovascular	Digoxin, ACEis, CCBs, amiodarone, methyldopa, spironolactone, reserpine, minoxidil
Psychiatric	Benzos, TCAs, phenothiazines, haloperidol, atypical antipsychotics
Misc	ARV for HIV, metoclopramide, penicillamine, phenytoin, sulindac, and theophylline

Clinical Presentation

• Concerning for malignancy when:
  • Unilateral
  • Peripheral rather than concentric areolar
  • Peau d'orange
  • Firm, hard, with irregular borders
  • Discharge

Investigations

• Labs
  • Estradiol and total or free testoterone
  • LH to differentiate primary vs secondary hypogonadism
  • Prolactin, to rule out prolactinoma
  • TSH for hyperthyroidism
  • hCG for certain tumours
  • Creatinine for kidney failure
  • Liver enzymes for liver disease
• Imaging
  • None routinely indicated

Management

• If the patient presents while the breast tissue is still growing and painful and has not fibrosed:
  • Tamoxifen for 3 months
• If the breast tissue has been present for years and is fibrosed and no longer growing:
  • Plastic surgery

Prognosis

• For newborns, expected to resolve
• For pubescent boys, expected to resolve in months

Further Reading

• Braunstein, GD. Gynecomastia. N Engl J Med. 2007;357:1229-1237.
• Johnson RE and Murad MH. Gynecomastia: Pathophysiology, Evaluation, and Management. Mayo Clin Proc. 2009;84(11):1010-1015.