Estrogen and Progestins Overview

Gonadal Hormones

• Gonadal hormones include estrogen, progesterone, and testosterone.
• Natural estrogens comprise Estradiol, Estrone, and Estriol.
• Synthetic steroids include Ethinyl Estradiol and Mestranol.
• Non-steroidal synthetics include Diethylstilbestrol and Dienestrol.

Physiological Actions of Estrogens

• Estrogens promote the synthesis of clotting factors II, VII, IX, X, fibrinogen, and anti-thrombin.
• Continuous estrogen exposure may lead to endometrial hyperplasia.
• Estrogens lower LDL and raise HDL cholesterol levels.
• They sensitize myometrium to oxytocin, aiding labor.
• Estrogens decrease bone resorption, impacting bone health.

Indications for Estrogen Use

• Treatment for hypogonadism in girls.
• Administered for hormonal replacement therapy.
• Used in contraception.
• Recommended for osteoporosis management.
• Useful in treating prostate carcinoma.
• Address conditions like Turner's syndrome (gonadal dysgenesis).

Adverse Effects of Estrogens

• Potential for gallstones and pulmonary embolism.
• Increased risks for endometrial and breast cancer associated with long-term use.
• Use of DES during pregnancy may increase vaginal adenocarcinoma risk in daughters.

Selective Estrogen Receptor Modulators (SERMs)

• Clomiphene: Enhances FSH/LH secretion by inhibiting estrogen feedback on hypothalamus/pituitary; used to induce ovulation; risks of multiple pregnancies.
• Tamoxifen: Acts as a partial agonist in certain tissues; used in advanced breast cancer, with endometrial cancer risk due to partial agonism.
• Raloxifene: Agonist for bone and lipid metabolism; antagonist for endometrium and breast; prevents post-menopausal osteoporosis without endometrial cancer risk.

Aromatase Inhibitors

• Anastrozole: Inhibits aromatase, reducing estrogen synthesis; indicated for post-menopausal breast cancer resistant to tamoxifen.

Progestins

• Synthetic analogs of progesterone are categorized by generation based on structure and potency.
• First generation: Norethindrone, Ethynodiol diacetate.
• Second generation: Levonorgestrel, Norgestrel.
• Third generation: Desogestrel, Norgestimate.
• Fourth generation: Drospirenone.

Clinical Uses of Progestins

• Administered for hormonal replacement therapy and contraception.

Adverse Effects of Progestins

• Possible effects include breakthrough bleeding, hirsutism, and acne (androgenic side effects).
• Alterations in lipid and glucose metabolism may occur.

Antiprogestins

• Mifepristone: Acts as a progesterone receptor antagonist and glucocorticoid receptor antagonist; effective in post-coital pregnancy prevention and early pregnancy termination.

Hormonal Contraceptives

• Two main types:
  • Combination of estrogen and progestin: Inhibits gonadotropin release, especially LH surge during midcycle.
  • Progestin-only options are also available.