Partial Estrogen Receptor Agonist

• Partial agonist-antagonist at some but not all target tissues

• Prevention of postmenopausal osteoporosis and prophylaxis of breast cancer

• Increased risk for venous thrombosis

Partial Estrogen Receptor Agonist

• Newer SERM

• Used in combination with conjugated estrogens

• Menopausal symptoms and prophylaxis of postmenopausal osteoporosis

Partial Estrogen Receptor Agonist

• Old partial estrogen agonist closely related to chlorotrianicene

• Ovulation-inducing agent

• Inhibit the action of stronger estrogens

Partial Estrogen Receptor Agonist

• Stimulates ovulation in women with oligomenorrhea/ amenorrhea and ovulatory dysfunction

• Blocks the feedback inhibitory influence of estrogens on the hypothalamus, causing a surge of gonadotropins, which leads to ovulation

Partial Estrogen Receptor Agonist

Adverse Effects:

• Mild hot flushes (similar to menopausal patients) which disappear with continued drug use

• Eye symptoms

• Ovarian enlargement

• Incidence of multiple pregnancy

Pure Estrogen Receptor Agonist

• Used for Tamoxifen-resistant breast cancer

Pure Estrogen Receptor Agonist

• Used for Tamoxifen-resistant breast cancer

Pure Estrogen Receptor Agonist

• 19-norsteroid antagonist that binds strongly to progesterone and glucocorticoid receptor

• Used as a contraceptive

• Termination of early pregnancy (major use)

• Effective emergency postcoital contraceptive

Pure Estrogen Receptor Agonist

• Potent experimental progesterone inhibitor and abortifacient (25 mg twice daily)

• Has antiglucocorticoid activity

Aromatase Inhibitors

• Nonsteroidal

• Effective in some women with tamoxifen-resistant breast tumors

Aromatase Inhibitors

• Oral, Nonsteroidal

• As effective as tamoxifen

• Used in breast cancer

• Adjunct to androgen inhibitors in the treatment of precocious puberty

• Primary treatment in the excessive aromatase syndrome

Synthesis Inhibitors

• Isoxazole derivative of ethisterone w/ progestational, androgenic, and glucocorticoid activities

• Inhibits the midcycle surge of LH and FSH and can prevent the compensatory increase in LH and FSH following castration in animals

• Does not significantly lower or suppress basal LH and FSH levels in normal women

Synthesis Inhibitors

• Binds to androgen, progesterone, and glucocorticoid receptors

• Inhibits P450scc involved in gonadal steroid synthesis

• Does not inhibit aromatase

Synthesis Inhibitors

Clinical uses:

• Treatment of endometriosis (major use)

• Fibrocystic disease of the breast

• Hematologic and Allergic disorders

Synthesis Inhibitors

Adverse effects

• Major: Weight gain, edema, decreased breast size, acne and oily skin, increased hair growth, deepening of voice. headache, hot flushes, changes in libido, and muscle cramps

• Can cause adrenal suppression

Contraindications

• Used in caution in patients with hepatic damage

• Contraindicated during pregnancy and breast-feeding