What causes gynecomastia?

From the Guidelines

Gynecomastia is primarily caused by an imbalance between estrogen and testosterone hormones in males, which can be triggered by various factors including certain medications, health conditions, and lifestyle factors. This condition occurs when there is either increased estrogen activity, decreased testosterone activity, or both, leading to enlarged breast tissue in men.

Common Causes of Gynecomastia

• Puberty: affecting up to 70% of adolescent boys
• Aging: affecting 30-65% of older men
• Obesity: where fat tissue converts testosterone to estrogen
• Certain medications: including antipsychotics, anti-androgens, some antibiotics, heart medications, and cancer treatments
• Illicit drugs: marijuana, heroin, amphetamines
• Alcohol abuse: which can damage the liver and alter hormone metabolism
• Health conditions: liver disease, kidney failure, hyperthyroidism, and certain tumors
• Genetic disorders: like Klinefelter syndrome Some studies suggest that spironolactone, a medication used to treat ascites, can cause or exacerbate gynecomastia 1. Additionally, certain health conditions such as pituitary adenomas can also lead to gynecomastia due to hormonal imbalances 1.

Treatment and Management

Treatment depends on the underlying cause and may include:

• Addressing the primary condition
• Discontinuing problematic medications when possible
• Weight loss for obesity-related cases
• Medication therapy with tamoxifen or surgical intervention in persistent cases Most cases of pubertal gynecomastia resolve spontaneously within 1-2 years without treatment. However, it is essential to identify and address the underlying cause to prevent long-term complications and improve quality of life. According to the most recent study, gynecomastia may be a marker for endocrine disorders, and virilization can be used to assess pubertal development and androgen status 1.

From the FDA Drug Label

5.4 Gynecomastia Spironolactone can cause gynecomastia. In 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.

Spironolactone can cause gynecomastia, with the risk increasing in a dose-dependent manner. Key points about spironolactone-induced gynecomastia include:

• Onset: varies widely from 1 to 2 months to over a year
• Reversibility: gynecomastia is usually reversible
• Incidence: about 9% of male subjects developed gynecomastia in the Randomized Spironolactone Evaluation Study 2

From the Research

Causes of Gynecomastia

• Gynecomastia is caused by an imbalance between estrogen and androgen action or an increased estrogen to androgen ratio, due to increased estrogen production, decreased androgen production or both 3
• The condition can be caused by drugs in 10 - 25% of all cases, with the pathophysiologic mechanism including exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia 4
• Other causes of gynecomastia include:
  • Pubertal gynecomastia
  • Obesity
  • Hypogonadism
  • Liver or renal failure
  • Thyrotoxicosis
  • Klinefelter syndrome
  • Tumors
  • Environmental pollutants 5
• Certain medications can also cause gynecomastia, including:
  • Sex hormones
  • Antiandrogens
  • Spironolactone
  • Cimetidine
  • Verapamil
  • Cancer chemotherapy
  • Diazepam
  • Tricyclic antidepressants
  • Neuroleptics
  • Calcium channel blockers
  • Captopril
  • Digitalis glycosides
  • Omeprazole
  • Some antibiotics
  • Growth hormone 4, 6
• Gynecomastia can also be caused by an underlying imbalance in hormonal physiology, with an increase in estrogen action relative to androgen action at the breast tissue level 7

Pathomechanisms

• The pathomechanism of gynecomastia involves an alteration in the androgen-estrogen ratio, along with the effects of other hormones including growth hormone, insulin like growth factor 1, prolactin, and other factors affecting aromatase enzyme 5
• The condition can be caused by a rise in prolactin level or an impaired balance in the serum estrogen/serum androgen ratio 6

Evaluation and Diagnosis

• Evaluation of gynecomastia must include a detailed medical history, clinical examination, specific blood tests, imaging and tissue sampling 3
• History and clinical examination will help formulate targeted investigations and management, including examination of breasts and testes, in addition to other parts of systemic examination 5