What are the causes of gynecomastia?

From the Guidelines

Gynecomastia is primarily caused by an imbalance between estrogen and testosterone levels in males, leading to enlarged breast tissue, with common causes including puberty, aging, obesity, and certain medications like spironolactone, as noted in studies such as 1 and 1. The condition can be triggered by various factors, including:

• Puberty, aging, and obesity
• Certain medications like spironolactone, ketoconazole, cimetidine, finasteride, and some antipsychotics
• Anabolic steroid use, marijuana, and alcohol consumption, especially with liver disease
• Medical conditions such as hypogonadism, hyperthyroidism, kidney failure, liver disease, and certain tumors that affect hormone production

According to the most recent and highest quality study, 1, gynecomastia can be caused by medications such as spironolactone, and the risk of gynecomastia can be reduced by using alternative medications like eplerenone. Addressing the underlying cause of gynecomastia is essential, and this may involve stopping triggering medications, treating medical conditions, losing weight if obesity is a factor, or reducing alcohol intake, as suggested by 1 and 1. In many cases, especially when medication-induced, gynecomastia will improve once the cause is addressed. It is also important to note that gynecomastia is a common entity, and approximately 50% of men with breast cancer may have coexisting gynecomastia, as mentioned in 1. However, gynecomastia is not believed to be a risk factor for male breast cancer, as stated in 1.

The development of gynecomastia is related to the balance between estrogen and testosterone levels, with estrogen stimulating breast tissue growth and testosterone inhibiting it, as discussed in 1 and 1. When this balance shifts, either from increased estrogen or decreased testosterone, breast tissue enlarges, leading to gynecomastia. In clinical practice, it is crucial to consider the potential causes of gynecomastia and to address the underlying cause to improve patient outcomes, as emphasized by 1 and 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.

The causes of gynecomastia include:

• Spironolactone 2: can cause gynecomastia, with a dose-dependent risk and an onset that varies from 1 to 2 months to over a year.
• Cimetidine 3: can 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 patients.

From the Research

Causes of Gynecomastia

The causes of gynecomastia can be attributed to various factors, including:

• Hormonal imbalance: An increase in estrogen action relative to androgen action at the breast tissue level 4, 5
• Medications: Certain drugs, such as spironolactone, cimetidine, ketoconazole, and anabolic steroids, can cause gynecomastia 6, 7
• Age-related reduction in testicular function: This can lead to an imbalance in hormonal physiology, resulting in gynecomastia 4
• Idiopathic causes: In some cases, the cause of gynecomastia may be unknown 4
• Underlying medical conditions: Certain conditions, such as hyperthyroidism or benign Leydig cell tumors of the testis, can cause gynecomastia 5

Drug-Induced Gynecomastia

Drugs are estimated to cause about 10-25% of all cases of gynecomastia 6. The following medications have been associated with gynecomastia:

• Spironolactone
• Cimetidine
• Ketoconazole
• Anabolic steroids
• Estrogens
• Human chorionic gonadotropin (hCG)
• Anti-androgens
• Gonadotropin-releasing hormone (GnRH) analogs
• 5-α reductase inhibitors

Other Causes

Other potential causes of gynecomastia include:

• Pubertal gynecomastia: A common condition that usually resolves spontaneously within 2 years 8
• Familial gynecomastia: A rare condition that can be inherited 5
• Testicular tumors: Certain types of testicular tumors can produce hormones that lead to gynecomastia 8, 5