What medications can cause gynecomastia?

Medications That Cause Gynecomastia

Spironolactone is the medication most strongly associated with gynecomastia, with approximately 10% of male patients developing this side effect, while other medications including antiandrogens, 5-alpha reductase inhibitors, certain antipsychotics, and various hormonal therapies also carry significant risk.

Common Medication Classes Associated with Gynecomastia

Cardiovascular Medications

• Aldosterone Antagonists

  • Spironolactone: Highest risk (10% in RALES trial) 1
  • Eplerenone: Lower risk alternative 1, 2

• Calcium Channel Blockers

  • Verapamil: Probable association 3
  • Nifedipine: Probable association 3
  • Amlodipine: Associated with dose-related pedal edema, more common in women 1

• Beta Blockers

  • Metoprolol, carvedilol, and other beta blockers: Less commonly associated 1

Hormonal Agents

• Antiandrogens: Very strong association (OR = 17.38) 4
• 5-alpha Reductase Inhibitors (finasteride, dutasteride): Significant association (OR = 1.77) 4
• Estrogens and hCG: Definite association 3
• Growth Hormone (hGH): Definite association 3
• GnRH Analogs: Definite association 3

Gastrointestinal Medications

• H2 Receptor Antagonists
  • Cimetidine: Definite association 3
• Proton Pump Inhibitors
  • Omeprazole: Probable association 3

Antifungal Agents

• Ketoconazole: Definite association 3

Psychiatric Medications

• Antipsychotics
  • Risperidone: Higher risk compared to other antipsychotics (OR = 4.32 vs. quetiapine) 4
  • Conventional antipsychotics: Associated with hyperprolactinemia 4

Other Medications

• HIV Medications
  • Efavirenz: Probable association 3
• Anabolic Steroids: Probable association 3
• Alkylating Agents (chemotherapy): Probable association 3
• Opioids: Probable association 3

Mechanism of Gynecomastia Development

Medications typically cause gynecomastia through one or more of these mechanisms:

1. Increasing estrogen activity: Direct estrogen administration or increased conversion of androgens to estrogens
2. Decreasing androgen activity: Blocking androgen receptors or reducing testosterone production
3. Elevating prolactin levels: Particularly with antipsychotics
4. Disrupting the estrogen-to-testosterone ratio: Most common underlying mechanism 4

Clinical Considerations

Risk Factors for Medication-Induced Gynecomastia

• Advanced age
• Liver disease
• Renal insufficiency
• Obesity
• Concurrent use of multiple medications that can cause gynecomastia
• Pre-existing hormonal imbalances

Management Options

1. Medication Adjustment:

   • Discontinue the offending medication when possible 5
   • Switch to alternatives with lower risk (e.g., eplerenone instead of spironolactone) 2
   • For spironolactone-induced gynecomastia, symptoms typically begin to resolve within a month of discontinuation 5

2. Alternative Medications:

   • For heart failure or hypertension: Eplerenone (25-50 mg daily initially, maintenance 50-100 mg daily) 2
   • For antipsychotic-induced gynecomastia: Consider prolactin-sparing alternatives 2

3. Surgical Options:

   • Consider for long-standing gynecomastia (>12-24 months) that doesn't respond to medication changes 2
   • Options include liposuction, direct excision, or combined approaches

Common Pitfalls and Caveats

1. Unilateral Presentation: Gynecomastia can present unilaterally and still be medication-induced 5

2. Delayed Onset: Gynecomastia may develop after months or even years of medication use, with onset varying from 1-2 months to over a year 6

3. Reversibility: While often reversible after medication discontinuation, long-standing gynecomastia may persist due to fibrotic changes

4. Differential Diagnosis: Always rule out pseudogynecomastia (fatty tissue deposition without glandular proliferation) and breast malignancy, particularly in older men 2

5. Monitoring: For patients on medications with high risk of gynecomastia (spironolactone, antiandrogens, 5-alpha reductase inhibitors), regular physical examination to detect early breast tissue changes is recommended 2

Remember that while medication-induced gynecomastia accounts for approximately 10-25% of all cases 3, other causes including physiologic changes, chronic diseases, and tumors should be considered in the differential diagnosis.