The Second Generation of Hormonal Contraceptives

Abstract

Until the middle of the 1960s, hormonal contraception and ovulation suppression were felt to be synonymous. The estrogens were thought to inhibit ovulation, while the progestin enhanced this antiovulatory action and regulated the growth of the uterine endometrium. Then Rudel, Martinez-Manautou, and Maqueo-Topete (1965, 1966), in Mexico City, undertook a systematic study of the role of certain progestins in preventing ovulation and of antifertility effects produced by progestin-induced alteration of the uterine endometrium and the cervical mucus. They observed suppression of ovulatory pregnanediol values in most cases when they gave 10 mg norethindrone in either estrogen-contaminated (0.7% mestranol content) or estrogen-free form. A similar result was obtained with the 17-acetoxyprogestin, chlormadinone acetate (table 4.1). The clear dose-response relationship led Rudel and Martinez-Manautou to speculate on the possibility of finding a progestin dose that would alter the structure and milieu of the reproductive tract sufficiently to be contraceptive but without inhibiting ovulation. The progestins investigated were shown to exert a suppressive influence on uterine endometrial development when given throughout a menstrual cycle (fig. 4.1). The degree of suppression was correlated with the relevant antiestrogenic activity of a particular compound (Rudel, Martinez-Manautou, and Maqueo-Topete 1965; Rudel et al., 1967).