Oral contraceptives have been in general use for only slightly more than a decade, but during this time a large volume of literature has accumulated concerning primarily the mechanisms of action and the adverse reactions of the estrogenic and progestagenic components of these drugs. In addition, numerous reports have been published concerning clinical studies in which these synthetic hormones have been employed for the purpose of contraception, but in dosage forms and on dosage schedules differing, sometimes markedly, from those of the commercially available oral contraceptives. The purposes of this review are to discuss and to summarize the more recent developments concerning these various aspects of hormonal contraception. However, since the mechanisms of action of the oral contraceptives involve modifications of the hormonal and hormone-related events occurring during the normal ovula-* Editor's nore: Part I1 of this article will appear in the March 1973 issue of the Journul o/Phurmuccuticul Sclcnces.tory menstrual cycle, such a review would be incomplete unless prefaced by a summary of these events.
GENERAL CONSIDERATIONSMenstrual Cycle-The recently increased accumulation of knowledge concerning hypothalamic-pituitaryovarian interrelationships in the human have been made possible as a result of the discovery of the hypothalamic-releasing hormones (factors) (1) and the development of competitive binding techniques (2) that permit the accurate measurement of the minute amounts of gonadotropins and gonadal steroid hormones present in as little as 1 ml. of serum.A number of recent reviews (1-15) summarized the observations made in numerous studies since the late 1960's. Briefly, gonadotropin [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] secretion by the anterior pituitary is under the control of the hypothalamus which secretes small polypeptides into the portal system connecting the median eminence of the hypothalamus with the anterior pituitary. These hormone-specific releasing factors (FSH-RF and LH-RF) [designated by some investigators as releasing hormones (FSH-RH and LH-RH) (l)] act on the pituitary to stimulate the release and, perhaps, also the synthesis of FSH and LH. Furthermore, evidence indicates that two hypothalamic centers may be responsible for LH release: a "tonic" center concerned with the regulation of basal LH secretion and a "clonic" ("cyclic") center responsible for triggering the ovulatory surge in LH secretion. The hypothalamus, in turn, is influenced by the estrogen and progesterone secreted by the ovary Vd. 62, No. 2, February 1973 179