What is the most common cause of gynecomastia in men?

Most Common Cause of Gynecomastia in Men

The most common cause of gynecomastia in men is physiologic (occurring in newborns, adolescents, and older men), followed closely by medication-induced gynecomastia, with idiopathic causes accounting for a substantial portion when no clear etiology is identified. 1, 2

Understanding the Epidemiology

Gynecomastia affects up to 57% of men during their lifetime, making it an extremely common condition 1. The distribution of causes varies by age group and clinical context 2:

Physiologic Gynecomastia (Most Common Overall)

• Occurs in three distinct life phases: newborns (due to maternal estrogen exposure), adolescents (pubertal hormonal fluctuations), and older men (age-related decline in testosterone with relative estrogen excess) 2
• Self-limited in most cases, particularly pubertal gynecomastia which typically resolves spontaneously 3, 2
• Represents the single largest category when considering all age groups together 2

Medication-Induced Gynecomastia (Most Common Pathologic Cause)

When excluding physiologic causes, medications represent the leading identifiable etiology 4, 5:

High-risk medications include:

• Spironolactone: Causes gynecomastia in approximately 9% of male patients at mean doses of 26 mg daily, with risk increasing in a dose-dependent manner 5
• Antiandrogens: Non-steroidal antiandrogens (bicalutamide, flutamide, nilutamide) commonly cause gynecomastia, with incidence as high as 80% in men on estrogen therapy for prostate cancer 4
• 5-alpha reductase inhibitors (finasteride, dutasteride) 4
• GnRH agonists or antagonists 4
• Ketoconazole (causes hypogonadism and gynecomastia) 4
• Digoxin (evidence is contradictory but association exists) 4
• Chronic cannabis use, especially when started at young age 4

Idiopathic Gynecomastia

• Accounts for a substantial portion of cases when no clear physiologic or pathologic cause is identified after thorough evaluation 1, 6

Pathophysiologic Mechanism

All causes ultimately result from an imbalance between estrogen and androgen action, either through 6, 7, 3:

• Increased estrogen production
• Decreased androgen production
• Altered estrogen-to-androgen ratio
• Increased peripheral conversion of androgens to estrogens (as seen in obesity and liver cirrhosis) 8

Less Common but Important Pathologic Causes

Endocrine Disorders

• Hypogonadism (primary or secondary) 8
• Hyperprolactinemia 8
• Thyroid disease (hyperthyroidism) 3

Systemic Diseases

• Liver cirrhosis (impaired estrogen metabolism) 8
• Renal insufficiency 2

Genetic Conditions

• Klinefelter syndrome (relative risk of 24.7 for gynecomastia) 8
• BRCA2 mutation carriers (higher risk) 8

Tumors (Rare)

• Testicular Leydig cell tumors 3
• Adrenal tumors or adrenocortical carcinomas (direct estrogen secretion) 8

Clinical Implication for Practice

When evaluating a man with gynecomastia, the diagnostic approach should prioritize 9, 8:

1. Age-based assessment: Determine if this represents physiologic gynecomastia (newborn, adolescent, or elderly) 2
2. Comprehensive medication review: Temporal relationship between medication initiation and gynecomastia onset 8
3. Underlying medical conditions: Assess for hypogonadism, thyroid disease, liver disease, or renal dysfunction 8
4. Hormonal evaluation: Measure serum estradiol in testosterone-deficient patients, with mandatory endocrinology referral if elevated 9

Important Caveat

Distinguish true gynecomastia from pseudogynecomastia (fatty tissue deposition rather than glandular proliferation), especially in patients with elevated BMI, as this distinction affects management 9, 8.