Inhibition of ovulation: comparison between the mechanism of action of steroids and GnRH analogues
Bouchard, P.; Wolf, J.P.; Hajri, S.
Human Reproduction 3(4): 503-506
1988
ISSN/ISBN: 0268-1161 PMID: 3292571 DOI: 10.1093/oxfordjournals.humrep.a136735Document Number: 359944
Recent developments in steroid research suggest the potential of steroids and gonadotropin-releasing hormone (GnRH) analogues and antagonists in blocking selective events in the menstrual cycle. GnRH analogues suppress gonadotropin secretion by inhibiting GnRH action at the pituitary level, while gonadal steroids regulate gonadotropin secretion both at the pituitary and hypothalamic levels. The pulsatile secretion of GnRH is achieved by the fine regulation of estrogens and progesterone. Progesterone is chiefly responsible for a negative feedback effect at the hypothalamic level, which decreases GnRH pulse frequency. Estradiol exerts both a positive and negative feedback effect, mostly at the pituitary level, and the use of steroids to prevent ovulation combines both effects. GnRH agonists suppress bioactive luteinizing hormone (LH) secretion and, to a lesser extent, that of follicle-stimulating hormone (FSH). The repeated administration of GnRH agonists blocks ovulation and prevents normal follicular development. Agonists such as Buserelin nasal spray and nafarelin have resulted in significant levels of amenorrhea, and GnRH agonists may provide an alternative for women over 35 years of age or those who are at risk from the use of steroids. GnRH antagonists are still in a developmental phase, but are able to suppress bioactive gonadotropin production by competing with endogenous GnRH for its receptors. Preliminary human data suggest that the administration of a GnRH antagonist during the follicular phase will inhibit ovulation. Unfortunately, the longterm administration of these compounds is contraindicated by their side-effect of a decrease in bone mass.