Chapter 48: Estrogens, Progestins, and the Female Reproductive Tract

INTRODUCTION

Estrogens and progestins are endogenous hormones that produce numerous physiological actions. In women, these include developmental effects, neuroendocrine actions involved in the control of ovulation, the cyclical preparation of the reproductive tract for fertilization and implantation, and major actions on mineral, carbohydrate, protein, and lipid metabolism. Estrogens also have important actions in males, including effects on bone, spermatogenesis, and behavior. Well-characterized receptors for each hormone mediate biological actions in both the unliganded and the liganded states.

The most common uses of estrogens and progestins are for contraception and menopausal hormone therapy (MHT) in women, but the specific compounds and dosages used in these two settings differ substantially. Antiestrogens are used in the treatment of hormone-responsive breast cancer and infertility. Selective estrogen receptor modulators (SERMs) that display tissue-selective agonist or antagonist activities are useful to prevent breast cancer and osteoporosis. The main use of antiprogestins has been for medical abortion.

Several naturally occurring and synthetic environmental chemicals mimic, antagonize, or otherwise affect the actions of estrogens in experimental test systems. The precise effect of these agents on humans is unknown but is an area of active investigation.

ABBREVIATIONS

ESTROGENS

Chemistry and Synthesis

Chemistry

Many steroidal and nonsteroidal compounds, some of which are shown in Table 48–1 and Figure 48–1, possess estrogenic activity. Estrogens interact with two receptors of the nuclear receptor superfamily, termed ERα and ERβ. The most potent naturally occurring estrogen in humans, for both ERα- and ERβ-mediated actions, is 17β-estradiol, followed by estrone and estriol. Each contains a phenolic A ring with a hydroxyl group at carbon 3 and a β-OH or ketone in position 17 of ring D.