Hypogonadism in men consuming sustained-action oral opioids

Naturally occurring opiates (endorphins) diminish testosterone levels by inhibiting both hypothalamic gonadotrophin releasing hormone production and testicular testosterone synthesis. Heroin addicts treated with a single daily dose of methadone and nonaddicts receiving continuous intrathecal opioids quickly develop low luteinizing hormone and total testosterone levels. A similar pattern was sought in men consuming commonly prescribed oral opioids. Free testosterone (FT), total testosterone (TT), estradiol (E(2)), dihydrotestosterone (DHT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in 54 community-dwelling outpatient men consuming oral sustained-action dosage forms of opioids several times daily for control of nonmalignant pain. Hormone levels were related to the opioid consumed, dosage and dosage form, nonopioid medication use, and several personal characteristics and were compared with the hormone analyses of 27 similar men consuming no opioids. Hormone levels averaged much lower in opioid users than in control subjects in a dose-related pattern (P < .0001 for all comparisons). FT, TT, and E(2) levels were subnormal in 56%, 74%, and 74%, respectively, of opioid consumers. Forty-eight men (89%) exhibited subnormal levels of either FT or E(2). Either TT or E(2) level was subnormal in all 28 men consuming the equivalent of 100 mg of methadone daily and in 19 of 26 (73%) consuming smaller opioid doses. Eighty-seven percent (39 of 45) of opioid-ingesting men who reported normal erectile function before opioid use reported severe erectile dysfunction or diminished libido after beginning their opioid therapy. Commonly prescribed opioids in sustained-action dosage forms usually produce subnormal sex hormone levels, which may contribute to a diminished quality of life for many patients with painful chronic illness.