Endogenous opioids and hypogonadism in human obesity

Abstract Massively obese males often show symptoms of hypogonadism, but the mechanism for this is unclear. Increased endogenous opioid inhibition of the hypothalamic GnRH pulse generator resulting in insufficient stimulation of the pituitary gonadotroph has been proposed as a possible mechanism. If this hypothesis is correct, obese males should be more sensitive to the LH-elevating effects of the opiate antagonist, naloxone, than men of normal weight and gonadal status. This study investigated the etiology of obesity-related hypogonadism by examining luteinizing hormone (LH) and follicle stimulating hormone (FSH) responses to gonadotropin-releasing hormone (GnRH) and to infusions of saline or naloxone. Subjects were five obese (201 ± 14% IBW ) and five normal weight (control) (97 ± 4% IBW ) males. Before treatment, obese males had significantly ( p ng / dl ), whereas estradiol, androstenedione, and dehydroepiandrosterone levels were not different between the two groups. Both groups showed equivalent elevations in LH (fourfold to sixfold) in response to GnRH stimulation, but obese patients had significantly lower basal ( p p p ng / ml during naloxone vs. 21.7 ± 1.8 ng / ml during saline, p pulses / h during saline infusion to 0.68 ± 0.13 pulses / h during naloxone treatment ( p