Description

• Benign glandular enlargement of male breast that is generally bilateral (may be asymmetric or unilateral):
  • Type 1: Benign adolescent hypertrophy; physiologic discoid subacute mass
  • Type 2: Physiologic gynecomastia; generalized enlargement to greater degree
  • Type 3: Stimulated by obesity
  • Type 4: Pectoral muscle hypertrophy
• System(s) affected: Endocrine/Metabolic; Skin/Exocrine
• Synonym(s): Male breast hypertrophy

Epidemiology

• Predominant age: Puberty; >65 years of age (especially with weight gain)
• Predominant sex: Male only

Pediatric Considerations
Transient gynecomastia is seen in neonatal boys.

Geriatric Considerations
Drug-induced form is more common in geriatric patients.

• 38–64% of pubertal males may have mild form. Usual onset is 11–12 years of age, with resolution by age 16–17 years.
• Nonpubertal forms are rare except when drug-induced.

Risk Factors

• Obesity
• Liver disease
• Renal disease
• Recovery from prolonged severe illness associated with malnutrition and weight loss (refeeding gynecomastia)
• Multiple therapeutic as well as nontherapeutic drugs (e.g., spironolactone, cimetidine, ranitidine, omeprazole, isoniazid, ketoconazole, amlodipine, captopril, diltiazem, enalapril, nifedipine, verapamil, diazepam, haloperidol, digitalis, statin drugs, anabolic steroids, androgens, estrogens, growth hormone, amphetamines, heroin, methadone, marijuana, and ethanol, among others) (1)
• Family history
• Exposures: Marijuana, alcohol, some medications (see “Etiology”)

Genetics
Some instances of familial gynecomastia may be inherited as a male-limited autosomal trait.

General Prevention

In men taking estrogen for prostate cancer: Low-dose radiation prior to institution of diethylstilbestrol

Pathophysiology

The cause of pubertal gynecomastia is not clear (2)[C]:

• May be related to transient imbalance of androgens and estrogens
• May be related to higher leptin levels (may result in altered local estrogen levels)

Etiology

• Physiologic: Transient in neonatal boys and at puberty:
  • 60–90% of newborn males develop transient breast enlargement related to transplacental estrogen.
  • In pubertal boys, may require 1–3 years to regress or may not regress at all
  • Men age 60–90 years may develop gynecomastia related to declining levels of testosterone.
• Exposure to a high level of estrogen compared with testosterone concentration
• Identifiable syndrome/cause found in 12% of pubertal boy
• Tumors: Estrogen-secreting, gonadotropin-secreting, prolactin-secreting pituitary adenomas, hepatic fibrolamellar carcinoma
• Drugs (10–25% of gynecomastia) (1): Hormones, marijuana, digitalis, spironolactone, cimetidine, ketoconazole, phenytoin, furosemide, verapamil, cytotoxic drugs, antihypertensives, sedatives, antidepressants, amphetamines, heroin, methadone, anabolic steroids (2)[C]
• Systemic disorders: Cirrhosis, thyrotoxicosis, renal failure
• Androgen production deficiency
• Androgen-insensitivity syndromes
• Idiopathic (25% of gynecomastia)

Commonly Associated Conditions

• Peutz-Jeghers syndrome
• Male pseudohermaphroditism
• Hyperthyroidism
• Hypothyroidism
• Hepatic disease
• Prostate carcinoma
• Adrenal neoplasms (adenoma or carcinoma)
• Renal disease or dialysis
• True hermaphrodism
• Klinefelter syndrome
• Testicular failure (enzymatic defects of testosterone production, androgen insensitivity)
• Testicular neoplasms (germ cell, Leydig cell, Sertoli cell tumors)