From the Guidelines
Gynecomastia is primarily caused by an imbalance between estrogen and testosterone effects on breast tissue, with medication causes including spironolactone, as seen in patients with heart failure, where the use of spironolactone can lead to gynecomastia in a small percentage of patients 1.
Common Causes of Gynecomastia
The most common causes of gynecomastia include:
- Physiologic changes during normal development, such as neonatal, pubertal, and aging-related gynecomastia
- Medications, including spironolactone, ketoconazole, cimetidine, finasteride, certain antipsychotics, and hormone therapies
- Underlying health conditions, such as hypogonadism, hyperthyroidism, liver disease, kidney failure, and certain tumors that produce estrogen or human chorionic gonadotropin
- Substance use, particularly anabolic steroids, marijuana, and alcohol
Mechanism and Evaluation
The underlying mechanism of gynecomastia involves either increased estrogen activity, decreased testosterone activity, or both, which stimulates proliferation of breast ductal tissue. In evaluating gynecomastia, it is essential to distinguish true glandular enlargement from pseudogynecomastia (fat deposition) and to identify potentially reversible causes through careful history-taking, physical examination, and sometimes laboratory testing.
Relevance of Recent Studies
A recent study published in 2023 found that the use of spironolactone, a medication commonly used in heart failure patients, can lead to gynecomastia in a small percentage of patients, with an absolute difference in frequency of 0.9% between the intervention and placebo arms 1. Another study published in 2001 noted that painful gynecomastia can develop in patients taking spironolactone, and that the new selective aldosterone receptor antagonist eplerenone may reduce the risk of gynecomastia 1.
Clinical Implications
In clinical practice, it is crucial to consider the potential causes of gynecomastia and to evaluate patients carefully to identify potentially reversible causes. The use of medications such as spironolactone should be carefully weighed against the potential benefits and risks, particularly in patients with heart failure. The decision to use spironolactone or other medications that may cause gynecomastia should be based on a thorough evaluation of the patient's individual risk factors and medical history, as well as the potential benefits of the medication 1.
From the Research
Gynecomastia Etiology
Gynecomastia is a benign proliferation of glandular tissue of the breast in males, resulting from an imbalance between estrogen and androgen action at the breast tissue level 2, 3, 4. The etiology of gynecomastia can be classified into different categories, including:
- Physiological causes: Gynecomastia can occur during three phases in the age distribution curve: the neonatal period, puberty, and senescence 2, 4.
- Pathological causes: Underlying pathological conditions, such as hypogonadism, can lead to gynecomastia 2, 5.
- Pharmacological causes: Certain medications, such as spironolactone, cimetidine, and ketoconazole, can induce gynecomastia 6.
- Idiopathic causes: In some cases, the cause of gynecomastia remains unknown 2, 4.
Risk Factors
Several risk factors can contribute to the development of gynecomastia, including:
- Age: Gynecomastia is more common in older adults 2, 4.
- Obesity: Excess body fat can lead to an increase in estrogen levels, contributing to gynecomastia 5.
- Medication use: Certain medications, such as those listed above, can increase the risk of gynecomastia 6.
- Hormonal imbalances: Imbalances in sex hormone levels, such as low testosterone or high estrogen, can contribute to gynecomastia 2, 5.
Associated Conditions
Gynecomastia can be associated with various conditions, including:
- Metabolic syndrome: The prevalence of metabolic syndrome is higher in patients with gynecomastia, particularly those with medication-induced or hypogonadal gynecomastia 5.
- Hypogonadism: Gynecomastia can be a symptom of underlying hypogonadism 5.
- Male breast cancer: Although rare, gynecomastia can increase the risk of male breast cancer 2.