Oral Contraceptives
Serious side effects esp older women (older than 35) who smoke/predisposed to thromboembolic disease or cv disease. Start with lowest possible doses. (ie low dose tri-phasic preparation).
Combination OC: ethinyl estradiol (most common) or — estrogen component. 19-nor steroid — progestin. Higher doses of estrogen used for OC than for ERT. Monophasic, biphasic, and triphasic help reduce total amount of steroids used.
MOA: prevention of ovulation. (possible effects on cervical mucus or implantation).
Progestin Only Contraceptives
Mini-Pill – low dose 19-nor progestin (norgestrel/norethindrone) taken qd.
Implants containing norgestrel (Norplant)
Medroxyprogesterone acetate (Depot Provera) as depot injection.
MOA: 50-60% ovulation; other effects on cervical mucus, ovum transport, implantation.
Side Effects: menstrual irregularities, amenorrhea, irregular bleeding, edema, weight gain, HA. Suppress LH/FSH, estrogen levels decrease. May predispose to osteoporosis, esp thin women.
Post Coital/Emergency Contraception
1. Yuzpe method – high dose OCs Ç 50 micrograms of ethinyl estradiol and .25 mg
levonorgestrel. 1st dose of OC (2 tabs) taken within 72 hours of sex. Second dose 12 hours later. 75-80% effective. N/V are side effects.
2. Other Method – use of progestin (mini-pill but higher dose) within 72 hours of sex.
Efficacy 75-80%.
Anti Estrogens & SERMS
Competitive antagonists at estrogen receptor in some tissues
Tamoxifen – SERM which has antagonist axns in breast and CNS, agonist in other tissues including bone, cardiovascular and endometrium. Widely used for breast cancer. Acts directly on cancer cells to block the growth promoting effects of estrogens. Used for 5 years prophylactically. Decreases risk of a second tumor in women with one tumor, but may increase uterine cancer.
Clomiphene – treats infertility. Interacts with estrogen receptors in hypothalamus/ pituitary to block the negative feedback due to endogenous estrogens. Elevate LH/FSH secretion, causes ovulation.
Raloxifene – (Evista) SERM. Prevents osteoporosis in post menopausal women. (Agonist on bone, no antagonist in endometrium/breast). May precipitate hot flashes, does not have cardiovascular benefits.
GnRH Analogs
GnRH normally a pulsatile secretion. Continuous administration — inhibits pituitary LH/FSH secretion. Suppresses ovarian steroid pdn in women and testosterone pdn in men. Used to treat endometriosis. (No androgenic effects seen with danazol treatment). Also used for prostate cancer in men. Potential contraceptive agents.
Aromatase Inhibitors
Inhibit aromatase catalyzed step in estrogen biosynthesis. Functional antiestrogens. Treat breast cancer by reducing estrogens.
Exemestane – irreversible aromatase inhibitor.
Anastrozole – irreversible aromatase inhibitor.
Mifepristone (RU-486) et al anti-progestins
Mifeprix/Mifepristone – medical abortions within 49 days of conception. PG administered 2 days after antiprogestin. Antiprogestin causes implanted blastocyst to detach and PG ensures its expulsion. SE = vaginal bleeding and cramps. Could be used as contraceptive during luteal phase to prevent implantation, for emergency contraception, and for treatment of breast cancer.
Tags: Aromatase Inhibitors, Clomiphene, Competitive antagonists, ethinyl estradiol, Medroxyprogesterone acetate, mestranol, Mifepristone, progestrin, Raloxifene, thromboembolic disease, tri-phasic preparation, Yuzpe method
