Decreased central opioid activity in premenstrual syndrome: Luteinizing hormone response to naloxone

Objective: To evaluate central opioid activity in women with prospectively documented premenstrual syndrome (PMS) and control women in the mid- and late luteal phases of the menstrual cycle. Methods: Blood was collected every 15 minutes 1 hours before (0800) and 2 hours after treatment (0900-1100). The treatment was administered in a randomized fashion and consisted of naloxone 1 or 4 mg or placebo, and blood was assayed for luteinizing hormone (LH). Baseline estradiol, progesterone, and prolactin were measured at 0800 and 0900 hours. Results: There was a significant increase in LH area under the curve and mean LH in response to naloxone in the midluteal phase in the controls (P < .001). The PMS subjects did not display a significant increase in LH concentration in response to naloxone in the midluteal phase. There were no significant LH responses to naloxone in either group in the late luteal phase. There were no significant differences in estradiol, progesterone, or prolactin concentrations or estrogen to progesterone ratios between groups. Conclusion: Control women have an enhanced central opioid tone during the midluteal phase that diminishes and becomes minimal in the late luteal phase of the menstrual cycle. In contrast, women with PMS have a loss of central opioid tone during the midluteal phase as indicated by the loss of LH response to naloxone. This attenuated central opioid tone in women with PMS as compared with asymptomatic control women may play a role in the pathophysiology of PMS.