Hypogonadism and methadone: Hypothalamic hypogonadism after long-term use of high-dose methadone

To assess the relationship between hypogonadism and long-term administration of high-dose methadone.

We present a case of a 47-year-old man with a history of heroin use and treatment with high doses of methadone (130 mg/day), who complained of gynecomastia and impotence. Baseline levels of serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), plasma testosterone, and prolactin were determined, and then the response of gonadotropin levels to stimulation with gonadotropin-releasing hormone (GnRH) was examined at 30, 60, 90, 120, and 180 minutes.

Basal values of testosterone, LH, and FSH were below normal levels, whereas prolactin was normal. After administration of GnRH, the patient had a suboptimal increase in LH levels and lack of a response of FSH. When the daily dose of methadone was decreased to 40 mg, the patient's libido returned, and LH, FSH, and testosterone levels increased.

These findings could indicate the presence of (1) a direct effect of methadone on the hypothalamus that leads to an alteration in normal gonadotropin pulse patterns, or (2) a selective effect of methadone on the anterior pituitary that alters its response to GnRH, with either mechanism leading to a reversible, dose-related depression of testosterone levels.