What medications can cause gynaecomastia?

Medications Causing Gynecomastia

Spironolactone, antiandrogens (flutamide, bicalutamide, nilutamide, cyproterone acetate), GnRH agonists, 5-alpha reductase inhibitors, estrogens, ketoconazole, and cimetidine are definitively associated with gynecomastia, with spironolactone being the most common culprit in general practice. 1, 2, 3

Medications with Definitive Evidence (Highest Quality)

Hormonal Agents - Highest Risk Category

Antiandrogens used in prostate cancer:

• Non-steroidal antiandrogens (flutamide, bicalutamide, nilutamide) cause significant gynecomastia in up to 39% of patients during monotherapy 4
• Steroidal antiandrogens (cyproterone acetate, spironolactone) commonly cause gynecomastia through androgen receptor blockade 1
• Androgen deprivation therapy can cause gynecomastia in up to 80% of patients on estrogen therapy 1

GnRH agonists and antagonists:

• These agents lead to hypogonadism and subsequent gynecomastia through testosterone suppression 1

5-alpha reductase inhibitors:

• Finasteride and dutasteride cause gynecomastia by altering the testosterone-to-estrogen ratio 1

Exogenous hormones:

• Testosterone and anabolic steroids cause gynecomastia through aromatization to estrogens 1
• Direct estrogen administration stimulates breast tissue growth 1
• Human chorionic gonadotropin (hCG) and human growth hormone (hGH) are definitively associated 3

Cardiovascular Medications

Spironolactone:

• The FDA label specifically warns that approximately 9% of male heart failure patients develop gynecomastia at a mean dose of 26 mg daily 2
• Risk increases in a dose-dependent manner with onset from 1-2 months to over a year 2
• Gynecomastia is usually reversible upon discontinuation 2
• For patients requiring mineralocorticoid receptor antagonists who develop gynecomastia, switch to eplerenone, which has significantly lower risk 1, 5

Calcium channel blockers:

• Verapamil and nifedipine are probably associated with gynecomastia 3

Digoxin:

• Evidence is contradictory regarding sex-specific adverse effects including gynecomastia 1

Gastrointestinal Medications

Acid-suppressing agents:

• Cimetidine is definitively associated with gynecomastia 3
• Omeprazole is probably associated 3

Antifungal Agents

Ketoconazole:

• Definitively causes hypogonadism and gynecomastia in men, which may limit prolonged treatment 1, 3

Psychotropic Medications

Antipsychotics:

• Risperidone is probably associated with gynecomastia through hyperprolactinemia 3
• Other neuroleptics can induce hyperprolactinemia leading to gynecomastia 1

Antidepressants:

• Tricyclic antidepressants are possibly associated 6

Chemotherapy Agents

Alkylating agents:

• Probably associated with gynecomastia 3

Antiretroviral Medications

HIV medications:

• Efavirenz is probably associated with gynecomastia 3

Substances of Abuse

Recreational drugs:

• Alcohol is probably associated with gynecomastia 3
• Opioids are probably associated 3
• Anabolic steroids definitively cause gynecomastia through aromatization 3, 7
• Cannabis use, especially when started young, may affect hormonal systems 1
• Marijuana, heroin, and amphetamines have been reported to induce gynecomastia 7

Mechanism-Based Classification

Drugs increasing estrogen or estrogenic activity:

• Estrogens, testosterone (via aromatization), anabolic steroids, hCG, hGH 1, 3

Drugs blocking androgen action:

• All antiandrogens (steroidal and non-steroidal), spironolactone, 5-alpha reductase inhibitors, GnRH agonists 1, 3

Drugs increasing prolactin:

• Antipsychotics (especially risperidone), other hyperprolactinemia-inducing medications 1, 3

Drugs with unclear mechanisms:

• Cimetidine, ketoconazole, calcium channel blockers, digoxin 3

Clinical Management Approach

When evaluating gynecomastia, distinguish true gynecomastia (glandular tissue proliferation) from pseudogynecomastia (fatty tissue deposition), especially in patients with elevated BMI 1

Primary management strategy:

• Discontinue the offending medication if clinically feasible 8, 7
• For spironolactone users, switch to eplerenone 1, 5
• Treat early for best outcomes, as gynecomastia becomes more difficult to reverse after 12 months 8

Important Caveats

The quality of evidence varies significantly—most drug-gynecomastia associations are based on case reports with poor quality evidence 3, 9. Only the medications listed above with "definitive" or "probable" associations have sufficient evidence from controlled studies. Drugs are estimated to cause 10-25% of all gynecomastia cases 3. The lack of standardized definitions of gynecomastia across studies limits the strength of associations for many medications 9.