Causes of Gynecomastia
Gynecomastia is primarily caused by an imbalance between estrogen and androgen action at the breast tissue level, resulting in glandular breast tissue enlargement. 1, 2
Physiological Causes
- Pubertal gynecomastia: Common during adolescence, typically resolves spontaneously
- Neonatal gynecomastia: Due to maternal hormones
- Aging-related gynecomastia: Associated with age-related decline in testicular function
Pathological Causes
Medication-Related Causes
- Spironolactone: Most strongly associated with gynecomastia, affecting approximately 10% of male patients 1
- Other medications:
- Hormone replacement therapies
- Antipsychotics
- 5-α reductase inhibitors
- Beta blockers (metoprolol, carvedilol) 1
Hormonal Imbalances
- Increased estrogen production
- Decreased androgen production
- Elevated prolactin levels
- Increased LH and hCG levels 3
Underlying Medical Conditions
- Liver disease: Impairs hormone metabolism
- Renal insufficiency: Affects hormone clearance
- Obesity: Increases peripheral conversion of androgens to estrogens
- Tumors: Can produce hormones that disrupt the estrogen-androgen balance 1, 4
Risk Factors
- Advanced age
- Liver disease
- Renal insufficiency
- Obesity
- Concurrent use of multiple medications that can cause gynecomastia
- Pre-existing hormonal imbalances 1
Important Clinical Considerations
Differential Diagnosis
- Pseudogynecomastia: Fatty tissue deposition without glandular proliferation
- Male breast carcinoma: Requires prompt evaluation, especially in men ≥25 years with breast pain 1
Warning Signs Requiring Further Evaluation
- Nipple discharge or retraction
- Axillary adenopathy
- Suspicious or irregular masses
- Focal asymmetry
- Microcalcifications 1
Diagnostic Approach
For men ≥25 years with breast pain, diagnostic mammography or digital breast tomosynthesis is recommended as the initial imaging study. Ultrasound is indicated when mammogram findings are indeterminate or suspicious 1.
Management Considerations
For medication-induced gynecomastia, consider alternative treatments:
- Eplerenone as a lower-risk alternative to spironolactone 1
- For persistent painful gynecomastia, antiestrogen therapy may be beneficial 5
- For long-standing gynecomastia (>12-24 months) unresponsive to medication changes, surgical options may be considered 1
Remember that at least 30% of males will experience gynecomastia during their lifetime, and most cases of pubertal gynecomastia resolve without treatment 2, 6.