Pharmacological and endocrine profiles of gestodene

Efforts to minimize oral contraceptive side effects have focused on the use of new dosage schemes and the synthesis of new steroids that can be used in safer, low-dose formulations. To determine whether the new progestogen gestodene offers an advantage in this regard, we studied its pharmacological and endocrine profiles. Gestodene was found to exhibit relative binding affinity and biological activity profiles similar to or better than those of progestogens in current use. Modulation by gestodene of luteinizing hormone-releasing hormone (LH-RH)-stimulated gonadotropin release in vitro and in vivo in a rat model system indicated that gestodene is some three times as biologically active as levonorgestrel. The borderline dose for inhibition of ovulation by gestodene was estimated in a total of 23 women with normal cycles. Levels of LH-RH, follicle-stimulating hormone, 17 beta-estradiol, and progesterone were estimated during the ingestion of various doses of gestodene. A dose of 30 micrograms of gestodene caused inhibition of ovulation in 11 out of 12 subjects, and eight out of 11 showed follicular maturation. When 40 micrograms of gestodene was taken, six out of seven women did not ovulate, and one out of seven had a cycle with luteal insufficiency. These data indicate that 40 micrograms of gestodene is the borderline dose for inhibition of ovulation. A combination of 75 micrograms gestodene with 30 micrograms ethinyl estradiol was found to inhibit ovulation in ten subjects, and no follicular maturation was noted.(ABSTRACT TRUNCATED AT 250 WORDS)