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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.



AF: activation function

CEE: conjugated equine estrogens

CHD: coronary heart disease

ER: estrogen receptor

ERα: estrogen receptor α

ERβ: estrogen receptor β

ERE: estrogen response element

FP: PGF receptor

FSH: follicle-stimulating hormone

GABA: γ-aminobutyric acid

GnRH: gonadotropin-releasing hormone

hCG: human chorionic gonadotropin

HDL: high-density lipoprotein

HERS: Heart and Estrogen/Progestin Replacement Study

HRT: hormone replacement therapy

HSDD: hypoactive sexual desire disorder

HSP: heat shock protein

IGF: insulin-like growth factor

IUD: intrauterine device

IUS: intrauterine system

IVF: in vitro fertilization

LDL: low-density lipoprotein

LH: luteinizing hormone

LNg: levonorgestrel, as in LNg-IUS

LNg14 or 20: LNg, 14 or 20 μg/24 h

LPA: lipoprotein A

MHT: menopausal hormone therapy

MPA: medroxyprogesterone acetate

NE: norepinephrine

OHSS: ovarian hyperstimulation syndrome

OPG: osteoprotegrin

PCOS: polycystic ovary syndrome

PG: prostaglandin

PR: progesterone receptor

PRE: progesterone response element

PRM: progesterone receptor modulators

SERM: selective estrogen receptor modulator

SHBG: sex hormone–binding globulin

WHI: Women’s Health Initiative


Chemistry and Synthesis


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.


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