The effects of a long-acting progestin on the hypothalamic-pituitary-ovarian axis in women with normal menstrual cycles.

This study was performed to determine how a long-acting, slow-release preparation of norethindrone (NET) affects the hypothalamic-pituitary-ovarian axis of normal ovulatory women. Ten women were studied during the luteal phase of their menstrual cycle, and again at six and twelve weeks following intramuscular administration of 100 mg NET microencapsulated in poly-D,L-lactide-co-glycolide. Serial LH samples, serum E, P, and NET were followed by a GnRH stimulation test. Compared to luteal phase values, six and twelve weeks of treatment with NET inhibited serum E2 and P while mean serum LH remained unchanged and mean serum FSH increased significantly (p < 0.05). LH pulse frequency after NET treatment was twice the rate (p < 0.01) as that of the luteal phase, whereas LH pulse amplitude was decreased significantly (p < 0.05). Finally, although there was no significant change in pituitary LH secretion in response to GnRH, NET treatment augmented FSH responsiveness to GnRH at the times studied. Preserved pituitary responsiveness to GnRH in NET-treated patients suggests that inhibited ovarian function results in an increase in GnRH pulse frequency but not GnRH pulse amplitude. Since the progestational milieu is maintained in these patients by NET treatment, the decrease in serum E2 may be responsible for the increase in GnRH pulse frequency. The presence of a critical level of E2 may be necessary for progestins to affect the hypothalamic GnRH pulse generator.