THE RESPONSE OF THE PITUITARY-OVARIAN AXIS TO PULSATILE ADMINISTRATION OF GONADOTROPIN-RELEASING-HORMONE IN LONG-TERM ORAL-CONTRACEPTIVE USERS

OBJECTIVE: Our purpose was to differentiate between pituitary and hypo thalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intrave nously at 90-minute intervals for 4 days to 14 long-term users of a co mbined oral contraceptive (30 mu g of ethinyl estradiol and 150 mu g o f levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours . The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 mu g gona dotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovari an ultrasonography was performed. RESULTS: After 4 days of pulsatile g onadotropin-releasing hormone administration every exogenous gonadotro pin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteiniz ing hormone and follicle-stimulating hormone levels increased signific antly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The lut einizing hormone response to a 100 mu g bolus of gonadotropin-releasin g hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not ch ange. CONCLUSION: Pituitary sensitivity is not impaired during oral co ntraceptive use, suggesting that oral contraceptives exert their negat ive feedback effects predominantly at the hypothalamic level.