Medicinal Chemistry as Foundation for Contraception, Birth Control, Family Planning and Fertility

Abstract

Contraception plays a pivotal role in birth control and family planning and thus affects millions of women not only in the U.S. but also world-wide. Efforts are made in the U.S. to reduce the percentage of unwanted pregnancies, i.e., 49%, which compares unfavorably with Western Europe's percentage of 34% [1,2]. Despite a vast and steadily-increasing literature on the issues of family planning and birth control, several questions are still awaiting clarification, especially with regard to medicinal chemistry, i.e., effects of chemical substances on human endocrinology. The following analysis aims at identifying problem areas in contemporary research and draws attention to flawed data in scholarly publications. Hormones: Endocrinology and ChemistryThe menstrual cycle of the female reproductive system is primarily under the control of the hypothalamic Gonadotropin Releasing Hormon (GnRH) and the hormons released by the anterior pituitary, i.e., Luteinizing Hormon (LH) and Follicle Stimulating Hormon (FH). The uterine cycle is divided into a proliferative phase and a secretory or luteal phase. The proliferative phase, also called preovulatory or follicular, is under the influence of estrogens stemming from the developing follicle and lasts from the 5th to the 14th day of the menstrual cycle. The secretory phase is under the influence of estrogen and progesterone from the corpus luteum and lasts from the 15th day to the 28th day. Late in the luteal phase the anterior pituitary and the endometrium produce prolaktin, whose function is not fully understood. The ovarian steroids like cholesterol, bile acids, and vitaminD contain the cyclopentanoperhydrophenanthrene nucleus. Figures 1 and 2 shows the biosynthesis and metabolism of estrogens as well as the precursor steroids Cholesterol and Pregnenolone. Ovarian Hormones: 17beta-estradiol, estrone, and estriol.The naturally occurring estrogens secreted by the theca interna and granulosa cells of the ovarian follicles, the corpus luteum, and the placenta are the following C 18 steroids: 17beta-estradiol, estrone, and estriol. These steroids do not have an angular methyl group attached to the 10 position or a Delta -3-keto configuration in the A ring [3,4].In the biosynthetic pathway they are formed from androgens, but they are also formed in the circulation by aromatization of androstenedione. The enzyme aromatase catalyzes both, the conversion of androstenedione to estrone and the conversion of testosterone to 17beta-estradiol (E2) [2]. 17beta-estradiol (E2), the major secreted estrogen, is in equilibrium in the circulation with estrone. Estrone ist metabolized to estriol, probably primarily in the liver. Estradiol is the most potent and estriol the least potent of the three estrogens.Estrogens: secretion and metabolism. The concentration of estradiol in the plasma during the menstrual cycle varies and reaches a first peak of approximately 200 pg/mL around day 13, i.e., just before ovulation, and a second peak of about 110 pg/mL around day 19-22, i.e., during the m...