What are the risk factors for developing gynecomastia?

From the Guidelines

Gynecomastia is primarily caused by hormonal imbalances, certain medications, recreational drugs, and underlying health conditions that affect hormone production, with the most significant risk factors including physiological changes during neonatal, adolescent, and aging periods, as well as the use of medications and substances that alter the balance of estrogen and testosterone in the body. The primary risk factors for developing gynecomastia include hormonal imbalances where estrogen levels are elevated relative to testosterone, which commonly occurs during puberty, middle age, and older adulthood 1. Certain medications significantly increase risk, including anti-androgens, some antipsychotics, HIV medications, cardiovascular drugs, and some antibiotics. Some key points to consider regarding gynecomastia risk factors include:

• Hormonal changes: Gynecomastia occurs physiologically in neonates and adolescents and with aging but can occur at any age as a side effect of many medications and recreational drugs, as a result of hormonal changes, and in the setting of chronic liver disease 1.
• Medications: The use of certain medications such as anti-androgens (e.g., spironolactone, finasteride), some antipsychotics (e.g., risperidone, haloperidol), HIV medications (e.g., efavirenz), cardiovascular drugs (e.g., digoxin, amiodarone, calcium channel blockers), and some antibiotics can increase the risk of gynecomastia.
• Recreational drugs and substances: Alcohol, marijuana, heroin, methadone, and anabolic steroids can also trigger gynecomastia.
• Health conditions: Conditions that affect hormone production such as hypogonadism, hyperthyroidism, kidney failure, liver disease, and certain tumors predispose individuals to this condition.
• Obesity: Excess fat tissue can convert androgens to estrogens, increasing the risk of gynecomastia.
• Genetic conditions: Klinefelter syndrome and other genetic conditions that affect testosterone production are additional risk factors. Understanding these risk factors is crucial because addressing the underlying cause, when possible, is the most effective approach to managing gynecomastia, and it is essential to identify and manage these risk factors to reduce the incidence of gynecomastia and improve the quality of life for affected individuals.

From the FDA Drug Label

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 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 risk factors for developing gynecomastia include:

• Dose-dependent manner: The risk of gynecomastia increases with the dose of spironolactone.
• Duration of treatment: Gynecomastia has been reported in patients treated for one month or longer with cimetidine.
• Pathological hypersecretory states: The incidence of gynecomastia is higher in patients being treated for pathological hypersecretory states, such as Zollinger-Ellison Syndrome, with cimetidine.
• Male subjects: About 9% of male subjects developed gynecomastia in a Randomized Spironolactone Evaluation Study 2.
• High doses of cimetidine: Reversible impotence has been reported in patients with pathological hypersecretory disorders receiving cimetidine, particularly in high doses, for at least 12 months 3.

From the Research

Risk Factors for Gynecomastia

The development of gynecomastia, which is the benign enlargement of male breast glandular tissue, can be attributed to various factors. These include:

• Hormonal imbalance, specifically an imbalance between estrogen and androgen action or an increased estrogen to androgen ratio, due to increased estrogen production, decreased androgen production, or both 4
• Physiologic conditions such as those occurring in newborns, adolescents, and older men 5
• Chronic conditions like cirrhosis, hypogonadism, and renal insufficiency 5
• Use of medications, supplements, or illicit drugs 5
• Tumors, although this is a rare cause 5
• Idiopathic factors, as more than 95% of gynecomastia cases in adolescents are idiopathic 6
• Secondary causes in adolescents, which may arise from uncommon pathological conditions, although these are relatively rare (less than 5%) 6
• Consumption of anabolic androgenic steroids (AAS), which plays a major role in the development of gynecomastia, especially in youngsters seeking to boost physical strength and improve appearance 7

Specific Conditions and Gynecomastia

Certain conditions have been linked to an increased risk of developing gynecomastia, including:

• Klinefelter's syndrome (KS) 8
• Hyperthyroidism 8
• Testicular or adrenal neoplasms 8
• Hypogonadism, whether primary or secondary 8
• Chronic liver or renal disease 8

Lifestyle and Gynecomastia

Lifestyle factors, such as the use of anabolic androgenic steroids, can significantly increase the risk of gynecomastia. For instance, bodybuilders and individuals with a history of recent weight gain are more likely to develop gynecomastia due to AAS use 7