The purpose of this study was to determine the prevalence of central hypogonadism and sexual dysfunction in male cancer survivors exposed to chronic high-dose oral opioid therapy. We studied 20 male patients with cancer-related chronic pain who were disease-free for at least one year. All patients consumed at least 200 mg-equivalent of morphine on a daily basis for at least one year. Participants completed the Sexual Desire Inventory questionnaire and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed. Serum testosterone levels were reduced in these patients. The median value was 140 ng/dL (normal 241-827). There was no compensatory increase in FSH and LH. The median FSH level was 3.5 mIU/mL (normal 1.4-18.1). The median LH level was 2.1 mIU/mL (normal 1.5-9.3). The mean dyadic sexual desire score was 23.9+/-15.7 (normal value, 42.8+/-8.9). The mean solitary sexual desire score was 1.3+/-1.9 (normal value, 10.6+/-1.9). Our data suggest that chronic exposure to high-dose oral opioid therapy may result in marked central hypogonadism and sexual dysfunction. Given the increasing use of long-term opioid therapy for chronic pain syndromes, further investigation into these findings is warranted.