What is the antifungal medication associated with gynecomastia: ketoconazole, amphotericin B, fluconazole, or miconazole?

From the Guidelines

Gynecomastia is a side effect of ketoconazole (option a). Ketoconazole, an antifungal medication, can cause gynecomastia (enlargement of breast tissue in males) because it inhibits enzymes involved in steroid hormone synthesis, particularly testosterone production, as seen in a study published in The Lancet Diabetes and Endocrinology in 2021 1. By blocking the cytochrome P450 enzyme system, ketoconazole reduces testosterone levels while increasing estrogen-to-testosterone ratios, which can lead to breast tissue development in males. This side effect is dose-dependent and more common with oral formulations rather than topical applications. Some key points to consider about ketoconazole include:

• It blocks multiple adrenal enzymes, including those involved early in the steroid biosynthetic pathway, which can lead to decreased gonadal steroid synthesis and hypogonadism in men 1.
• Men may experience gynecomastia, which can limit prolonged treatment with ketoconazole 1.
• The other antifungal medications listed (amphotericin B, fluconazole, and miconazole) have different mechanisms of action and are not typically associated with gynecomastia as a common side effect. Patients taking ketoconazole should be monitored for this side effect, especially during long-term therapy.

From the Research

Gynecomastia Side Effects

• Gynecomastia is a side effect of certain medications, including:
  • Ketoconazole, an antifungal drug, which has been shown to cause gynecomastia in some patients by inhibiting androgen and glucocorticoid synthesis and increasing the estradiol-testosterone ratio 2, 3, 4
• Other medications that have been associated with gynecomastia include:
  • Spironolactone, cimetidine, hGH, estrogens, hCG, anti-androgens, GnRH analogs, and 5-α reductase inhibitors, which have a definite association with gynecomastia 3
  • Risperidone, verapamil, nifedipine, omeprazole, alkylating agents, HIV medications (efavirenz), anabolic steroids, alcohol, and opioids, which have a probable association with gynecomastia 3

Medications Not Directly Associated with Gynecomastia

• There is no evidence to suggest that amphotericin B, fluconazole, or miconazole are directly associated with gynecomastia 2, 3, 5, 4, 6