Opioid control of LH secretion in humans: menstrual cycle, menopause and aging reduce effect of naloxone but not of morphine.

A number of studies have been made on the role played by endogenous opioid peptides in the secretion of LH in humans. However no previous studies have compared the effects of the most potent pharmacological agonist and antagonist, morphine and naloxone, in the same subjects. The present study examined the acute effects of injections of morphine and naloxone on plasma LH levels in 30 healthy subjects (18 women and 12 men). Fertile women were subdivided into follicular (n = 6) and luteal (n = 6) phase groups; the remaining 6 were postmenopausal women. The 12 men were sub-divided in two groups of 6 subjects according to age (24-33 years, and over 60 years). There was a two day interval between injection studies in the same subjects. Morphine significantly decreased plasma LH levels in all groups examined (P less than 0.01). On the other hand, naloxone caused a significant increase in plasma LH levels in fertile women during the luteal phase of the cycle, but not during the follicular phase or in postmenopausal subjects, and in young but not in aged men (P less than 0.01). These results indicate that in humans there is a change in the activity of the opioids regulating LH secretion during the menstrual cycle, after menopause and in aged men and that these may be studied by the use of naloxone. The inability of naloxone under certain conditions to increase LH levels reflects the decreased activity of the endogenous system, while morphine, being active in all the subjects, seems to be less discriminative, at least in physiological conditions.