Hormonal contraception, past, present, and future part 1: the early path - facts, stories, and controversies.

Introduction: Marketing in the late 1950s of Combined Oral Contraceptives (COC) represented the achievement of centuries of research in reproductive endocrinology that included the isolation of the main steroids produced, within the concept of 'internal secretion,' by the ovaries and corpus luteum.

Areas covered: Key observations made at the end of the 19th century proved that the presence of corpus luteum induces temporary infertility in animals and that ovaries secrete hormonally active substances. During the 1930s, the four main hormones (progesterone, estrone, estradiol, and estriol) were identified and their structure determined. The recognition that natural compounds are not effective when given orally, stimulated the search for synthetic steroids. Ethinyl-estradiol, synthesized in 1937, remains even today the most widely used estrogenic component of COC, although other compounds (micronized estradiol, estradiol valerate, estetrol) have been incorporated in COC. A variety of synthetic progestins have become available since the early 1950s having different progestogenic potency, pharmacokinetic and pharmacodynamic properties.

Expert opinion: Started with observations made three centuries ago, development of COC has gone beyond the dream of the early investigators: literally dozens of formulations are available today capable of satisfying the needs of the majority of women of fertile age and the work continues.