Anti-estrogenic effects of contraceptive progestins on the dynamics of gonadotropin release

The hypophysiotropic effects of ethinylestradiol (EE) alone and in combination with three different progestins at various doses were assessed in 39 normal women. The compounds were given orally for 7 to 21 days. Serum LH and FSH were measured before and after GnRH double stimulation (2 x 25 micrograms i.v. at a two-hour interval); the ratio between second and first response served as an index of gonadotropin-synthesis capacity. Compared to pretreatment early follicular phase controls (LH and FSH ratios of 1.3 and 1.4), administration of 40 and 50 micrograms of EE daily elicited a significant amplification of LH and FSH synthesis (LH ratios of 2.2 and 3.3; FSH ratios of 2.8 and 3.3). By contrast, 80 micrograms of EE daily caused little change. The EE-induced rise of pituitary responsiveness to GnRH could be counteracted by the addition of progestins. The degree of inhibition as dependent on the type and dose of the progestational compound. It is concluded that the standardization GnRH double stimulation technique may serve as a pharmacodynamic model to quantitate the estrogenic and anti-estrogenic effects of contraceptive steroids at the pituitary level.