Gynecomastia - Causes

Causes

Gynecomastia is caused by excessive estrogen actions and is often the result of an increased ratio of estrogen to androgen. In approximately 25% of cases, the cause of gynecomastia is unknown.

About 10%-25% of cases are estimated to result from the use of medications. This is known as non-physiologic gynecomastia. Those medications include ketoconazole, cimetidine, gonadotropin-releasing hormone analogues, human growth hormone, human chorionic gonadotropin, antiandrogens such as bicalutamide, flutamide, and spironolactone, and 5-alpha-reductase inhibitors such as finasteride or dutasteride. Medications with probable associations to gynecomastia include risperidone, calcium channel blockers such as verapamil and nifedipine, anabolic steroids, alcohol, opioids, efavirenz, alkylating agents, and omeprazole. Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia. Hyperprolactinemia has also been associated with the development of gynecomastia.

Other causes of gynecomastia may include:

Hypogonadism

Conditions that interfere with normal testosterone production, such as Klinefelter syndrome or pituitary insufficiency, can be associated with gynecomastia.

Aging

Hormone changes that occur with normal aging, such as declining testosterone levels, can cause gynecomastia. This is also known as senile gynecomastia and is typically found in men between the ages of sixty and eighty.

Tumors

Testicular tumors such as Leydig cell tumors or Sertoli cell tumors (such as in Peutz-Jeghers syndrome) may result in gynecomastia. Other tumors such as adrenocortical tumors, pituitary gland tumors (causing Cushing's disease), or bronchogenic carcinoma, can produce hormones that alter the male-female hormone balance and cause gynecomastia.

Hyperthyroidism

In this condition, the thyroid gland produces too much of the hormone thyroxine and is thought to influence the level of sex-hormone binding globulin. 10-40% of individuals with hyperthyroidism may experience gynecomastia; returning to a normal thyroid state leads to resolution of the gynecomastia within a few months.

Kidney failure

Renal failure patients often experience a state of malnutrition, which may contribute to gynecomastia development. Dialysis may attenuate malnutrition of renal failure. Additionally, many renal failure patients experience a hormonal imbalance due to the suppression of testosterone production and testicular damage from high levels of urea also known as uremia-associated hypogonadism.

Liver failure and cirrhosis

In individuals with liver failure or cirrhosis, the liver's ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcohol may also contribute to a higher estrogen to testosterone ratio.

Malnutrition and starvation

When the human body is deprived of adequate nutrition, testosterone levels drop, and the liver's ability to degrade estrogen is diminished, causing a hormonal imbalance. Gynecomastia can occur once normal nutrition resumes but usually resolves within one to two years. Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia.

Neonatal breast development

Many newborn infants of both sexes show breast development at birth or in the first weeks of life. This occurs in about 60-90% of males and is believed to be due to maternal or placental estrogens but may be a response to the infant's own steroid hormones. In some infants fluid ("witch's milk") can be expressed. The breast development can last from weeks to months.