AGE-RELATED DECREASE IN THE OPIOID CONTROL OF LH-SECRETION DURING REPRODUCTIVE YEARS IN NORMAL WOMEN

Our previous studies showed that naloxone is unable to stimulate LH se cretion in elderly men, suggesting a loss in the endogenous opioid inh ibitory control of LH in senescence. Methods: In the present study, we examined whether increasing age during the reproductive period in wom en is associated with alterations in the LH-releasing effect of naloxo ne. Studies were performed in younger (age 20-28 years, n = 8) and old er (age 40-48 years, n = 8) subjects with normal menstrual cycles and normal gonadal steroid levels to avoid the interference of premenopaus e or menopause on gonadotropin secretion. The LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h) was tested not only in normal conditions, but also after chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days), because this treatment has b een found able to restore normal LH responses to naloxone in elderly m en. All tests were performed on the 22nd day of normal menstrual cycle s. Results: Naloxone induced a 100% increase in plasma LH levels in th e younger group. In contrast, naloxone enhanced only by 50% LH secreti on in the older subjects. When experiments were repeated after bromocr iptine treatment, the effect of naloxone did not change in the younger subjects, whereas it was significantly higher in the older group. In the presence of bromocriptine, naloxone-induced LH increment in the ol der group was indistinguishable from that observed in the younger grou p. These data suggest that during the reproductive period, increasing age is associated with an impairment in the endogenous opioid control of LH secretion. In addition, age-related dopaminergic alterations ind ependent of circulating gonadal steroid levels appear to underlie the defective endogenous opioid control of LH secretion in normally cyclin g women.