Inhibition of ovulation: comparison between the mechanism of action of steroids and GnRH analogues.

The pulsatile secretion of GnRH is achieved by the fine regulation of oestrogens and progesterone. Progesterone is mainly responsible for a negative feedback effect at the hypothalamic level which decreases GnRH pulse frequency. Oestradiol exerts both a positive and a negative feedback effect, mostly at the pituitary level, and the use of steroids to prevent ovulation combines both effects. Recent developments in steroid research suggest a potential interest in the use of non-androgenic progestins which reproduce the negative feedback effect of progesterone with fewer metabolic side effects. GnRH agonists, although responsible for low plasma levels of oestradiol, may be useful in women at risk for steroid contraception. GnRH antagonists suppress transient gonadotrophin-dependent events in the menstrual cycle. Studies with the second generation GnRH antagonist, Nal--Glu, suggest a potential use of these compounds in suppressing ovulation.