Bind to estrogen response elements to activate gene transcription

Autocrine and paracrine actions

Activate intracellular signaling pathways

Enhanced coagulation, uterine

bleeding, cancer, breast

tenderness, migraine headaches, cholestasis, gallbladder disease, hypertension

Rx: Primary hypogonadism, Postmenopausal hormonal therapy (bone loss, ↑ LDL), suppress ovulation (intractable dysmenorrhea, hirsutism, amenorrhea)

CI: estrogen-dependent neoplasms

(endometrium, breast), undiagnosed genital bleeding, liver disease, thromboembolic disorder, smokers

Bind to progesterone response element to activate gene transcription

↓Na⁺  reabsorption, ↑body temp

↑BP, ↓HDL, combined progestin and estrogen therapy in postmenopausal women may ↑risk of breast cancer

Hormonal contraceptives: thromboembolism, cholestatic jaundice, depression

Rx: hormone replacement therapy, hormonal contraception, dysmenorrhea, endometriosis, test estrogen secretion

Bind to the intracellular androgen receptor

Growth, differentiation, & synthesis of enzymes and other functional proteins

Rx: gynecologic disorders, reverse protein loss (after trauma, surgery, prolonged immobilization), anemia, osteoporosis, growth stimulators, aging

First selective estrogen receptor modulator (SERM)

Partial agonist inhibitor of estradiol at the estrogen receptor

Hot flushes, nausea, vomiting;

Prevents expected loss of bone density and ↑atherosclerosis after menopause, but may ↑risk of endometrial cancer

Breast cancer (35% reduction of contralateral breast cancer for first 5 years), chemoprevention of breast cancer in high-risk women

Another selective estrogen receptor modulator (SERM) at some but not all target tissues

Similar effects on lipids and bone, but does not stimulate endometrium or breast

Prevention of postmenopausal osteoporosis and prophylaxis of breast cancer in women with risk factors

Partial agonist at estrogen receptors (SERM); inhibit action of stronger estrogens

Inhibits estrogen receptors in the hypothalamus, thereby inhibiting negative feedback of estrogen on gonadotropin production = causes surge of gonadotropins which leads to ovulation

Hot flashes, eye symptoms, reversible hair loss, ovarian enlargement, multiple pregnancy (10%)

Cataracts

Induce ovulation (in women with oligomenorrhea, amenorrhea, ovulatory dysfunction, polycystic ovary syndrome)

Binds strongly to progesterone receptor and inhibits activity of progesterone; luteolytic effect

Vomiting, diarrhea, abdominal or pelvic pain, vaginal bleeding requiring intervention (5%)

Emergency postcoital contraceptive

Inhibits 5α-reductase, thereby inhibiting conversion of testosterone to dihydrotestosterone

Impotence, abnormal sexual function/ED, gynecomastia

Benign prostatic hyperplasia

Competitive antagonist at androgen receptor

Mild gynecomastia is frequent, reversible heptatic toxicity

Prostatic carcinoma, management of excess androgen effect in women