OPIOIDERGIC REGULATION OF LH PULSATILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

Women with polycystic ovary syndrome (PCO) display disordered patterns of LH pulsatility and may have an impairment of opioidergic regulation of GnRH‐LH. In order to ascertain if these patterns reflect an inherent hypothalamic abnormality or a functional state consequent to the acyclicity of sex steroids, LH pulsatility and gonadotrophin responses to naloxone were examined in six PCO women before and after treatment with incremental daily doses of a progestogen, medroxyprogesterone acetate (MPA), for 10 days to determine (i) if progestogen treatment would alter the LH pulse pattern to resemble that of the luteal phase; and (ii) if the conversion to a luteal phase LH pulse pattern by MPA would involve the induction of opioidergic regulation. LH pulsatility and FSH levels were determined by blood sampling at 10 min intervals for 8 h before and after MPA treatment during a saline infusion on the control day and during a naloxone infusion (1.6 mg/h) on the following day. Basal levels of oestradiol, oestrone. androstenedione, testosterone, and dehyd‐roepiandrosterone‐sulphate were measured before and after MPA. All six PCO women responded to MPA administration with a significant reduction in LH pulse frequency (P<0.005), an increase in LH pulse amplitude (P<0.0025), and an increase in LH pulse duration (P<0.025), without changes in mean LH, mean FSH, androgen, or oestrogen levels. Thus, a luteal phase LH pulse pattern was induced by MPA. Naloxone reversed the MPA‐induced changes in LH pulsatility, indicating that these responses involved the induction of central opioidergic activity. These results suggest that progestogen modulation of LH pulsatility in PCO women is similar to that of cycling women. The establishment by MPA treatment of opioidergic regulation of GnRH‐LH pulsatility implies that the opioidergic impairment seen in PCO women is a functional state