What causes gynecomastia?

From the Guidelines

Gynecomastia is primarily caused by an imbalance between estrogen and testosterone hormones in males, resulting in enlarged breast tissue, and can be triggered by various factors including hormonal changes, certain medications, health conditions, and substance use. These factors can lead to increased estrogen activity, decreased testosterone activity, or both, stimulating breast tissue growth. Some of the key factors that contribute to gynecomastia include:

• Hormonal changes during puberty, aging, or other conditions that affect hormone balance
• Certain medications such as spironolactone, ketoconazole, cimetidine, finasteride, certain antipsychotics, and some HIV medications, as noted in studies like 1 and 1
• Health conditions like liver disease, kidney failure, hyperthyroidism, and certain tumors
• Recreational substances such as alcohol, marijuana, heroin, methadone, and anabolic steroids

The underlying mechanism of gynecomastia involves the disruption of the normal balance between estrogen and testosterone, leading to the growth of breast tissue. In many cases, particularly during puberty, gynecomastia resolves on its own within six months to two years. However, persistent cases may require addressing the underlying cause, discontinuing problematic medications when possible, or in some cases, medical treatment with medications like tamoxifen or surgical intervention, as discussed in 1 and 1. It's also important to differentiate gynecomastia from other conditions, such as pseudogynecomastia, which is due to excess fatty tissue deposition in the breasts, and to consider the appropriate imaging approaches for symptomatic male breast conditions, as recommended in 1.

From the FDA Drug Label

Spironolactone can cause gynecomastia. In a Randomized Spironolactone Evaluation Study, patients with heart failure treated with a mean dose of 26 mg of spironolactone once daily, about 9% of the male subjects developed gynecomastia. The risk of gynecomastia increases in a dose-dependent manner with an onset that varies widely from 1 to 2 months to over a year. Gynecomastia is usually reversible. Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0. 3% to 1% in various studies.

Gynecomastia Causes:

• Spironolactone can cause gynecomastia, with a dose-dependent risk and an onset that varies from 1 to 2 months to over a year 2.
• Cimetidine can also cause gynecomastia, particularly in patients treated for one month or longer, with an incidence of about 4% in patients with pathological hypersecretory states and 0.3% to 1% in other cases 3. Key Points:
• Gynecomastia is usually reversible.
• The risk of gynecomastia increases with the dose of spironolactone.
• Cimetidine can cause gynecomastia, especially in patients with pathological hypersecretory states.

From the Research

Causes of Gynecomastia

Gynecomastia is a condition characterized by the proliferation of glandular breast tissue in men, resulting from an imbalance of hormonal physiology with an increase in estrogen action relative to androgen action at the breast tissue level 4. The causes of gynecomastia can be categorized into several groups, including:

• Physiologic causes: Gynecomastia is common in adolescents and adults, and can occur due to age-related reduction in testicular function or idiopathic causes 4.
• Pathological causes: Certain medical conditions, such as cirrhosis, hypogonadism, and renal insufficiency, can lead to gynecomastia 5.
• Medication-induced causes: Various medications, including spironolactone, cimetidine, ketoconazole, and anabolic steroids, have been associated with the development of gynecomastia 6, 7.
• Drug and substance use: The use of certain substances, such as alcohol, opioids, and HIV medications, may also contribute to the development of gynecomastia 7.

Specific Causes

Some specific causes of gynecomastia include:

• Anabolic steroid use: Consumption of anabolic steroids is a known cause of gynecomastia, with a high prevalence of 52% reported in one study 6.
• Hormonal imbalance: An imbalance of estrogen and androgen hormones can lead to gynecomastia, particularly in cases where there is an increase in estrogen action relative to androgen action at the breast tissue level 4, 8.
• Tumors: In rare cases, gynecomastia can be caused by tumors, such as those affecting the testes or adrenal glands 8, 5.

Evaluation and Treatment

The evaluation of gynecomastia can be accomplished through history, physical examination, and laboratory tests 4. Treatment options for gynecomastia include discontinuing use of contributing medications, treating underlying disease, and using medications such as estrogen receptor modulators or surgery in select patients 4, 7, 5.