[Synergism and antagonism between estrogens and progestins: an update]

Our purpose is to provide a review of studies performed since forty five years, concerning interactions of natural or synthetic estrogens and progestins. In this paper, the terms synergism and antagonism have to be considered in a broader sense than usually done. In addition to the classical concepts of succession and of simultaneity synergism between estradiol and progesterone, notions of "saving" and of "necessity" synergism came from decidualization studies in the rabbit (1949). The necessity synergism put definitively and end to the idea that estradiol was only a female hormone and progesterone a mother one. Our research in the field of ovum implantation showed also that estrogens might be secreted by mammalian ova (1949), which is now well established. The participation of estrogens to the process of decidualization in the rat suggested even (1958, 1959) their role in the starting implantation. From 1960, synthetic estrogens and progestins were tested, in a first step especially ethynylestradiol and chlormadinone acetate. In the rabbit and in the rat, these new tools permitted us to dissociate the hormonal needs of embryonic growth and of morphogenesis (1965). The studies related to the effects of these analogs upon the adrenal gland, as upon the hypophysis (1963), led to their clinical use in the treatment of advanced breast cancers, and the studies concerning their effects in the ovulation to the discovery of the antiovulatory synergism of synthetic estrogens and progestins (1966, 1982). These observations are in agreement with the Courrier rules with regard to the relationships between the relative, but also absolute, quantities of estradiol and of progesterone administered, and the obtained biological effects. Nevertheless, progestins exist with incomplete or, on the contrary, superfluous pharmacological activities. In the extreme, the estrogenic properties of norethisterone take precedence over its progestogenic properties when administered doses are growing (1977). These phenomena have now to be understood at a molecular level. Though explanations are presently available for some processes, many of them remain to day unexplained, and inversely other explanations are coming into sight.