Evidence against the involvement of opiate neurons in mediating the effect of clomiphene citrate on gonadotropin-releasing hormone neurons*†‡*Presented in part at the Twenty-Eighth Annual Meeting of the. Endocrine Society of Australia, August 26 to 28, 1985, Adelaide, Australia.†Supported in part by the National Health and Medical Research Council of Australia.‡Part of this material formed the basis of a fourth-year medical student elective (J. A.).

This study was designed to assess whether the hypothalamic action of clomiphene citrate (CC) on gonadotropin-releasing hormone (GnRH) neurons required activity of opiate neurons. Ten women were studied in two successive cycles. In the first cycle they infusion of saline or naloxone (2mg intravenous bolus followed by 1.6mg/hour) for 9hours, in random order on days 5 and 6 of the cycle. In the second cycle each woman was treated with CC (100mg) for 5days before study on day 6. In each study, blood samples were collected at 15-minute intervals for 9hours; during the last hour 10μg GnRH was given to test the pituitary response. After CC, luteinizing hormone (LH) pulse frequency was accelerated, and mean serum LH, serum follicle-stimulating hormone, and estradiol increased, but the pituitary response to GnRH was unchanged. These changes are best explained by an increase in activity of GnRH neurons. Conversely, naloxone had no effect on LH pulsatility or the pituitary response to GnRH. This indicates that the action of CC at least during the early follicular phase is exerted primarily at the levels of the hypothalamic GnRH pulse generator and does not depend on the activity of opiate neurons.