Sex Hormones Flashcards
(30 cards)
Therapeutic Estrogens
Estradiol, Ethinyl-estradiol, Estrone
Indications: primary hypogonadism, postmenopausal hormonal therapy, oral contraceptives, suppress ovulation in patients with intractable dysmenorrhea or hirsutism, fertility treatments
Side Effects: nausea, fluid retention, breakthrough bleeding, change in menstrual flow, breast tenderness
Adverse Effects: thromblytic complications; endometrial/breast carcinoma; HTN (IN MEN: feminization of genitalia & impotence)
Contraindications: pregnancy, incomplete bone growth, undiagnosed genital bleeding, stroke, thrombophlebitis, thromboembolic disease, heart disease; women with Hx of breast/uterine CA (BRCA gene)
DRUG INTERACTIONS: Decrease efficacy of anticoagulants and hypoglycemics; increase effects of tricyclic antidepressants; increase effects of oxytocin on uterus; St. John’s wort may lose efficacy of contraceptive or HRT of estrogens
Estradiol
Therapeutic estrogen
- main estrogen in premenopausal women
- poor oral bioavailability
- effective as a patch (ESTRADERM, ESTROGEL)
- IM lasts for weeks (DEPO Estradiol
- Topical with vaginal cream (Estring)
Ethinyl-esradiol
Therapeutic Estrogen
- commonly used for orl contraceptives
Estrone
Therapeutic Estrogen
- natural estrogen-main ingredient of conjugated estrogens (PREMARIN)
HRT Formations
DON’T HAVE TO KNOW ALL FOR TEST- JUST KNOW THAT MANY FORMS EXIST, including those in cream and patch forms, not just oral
Estrogen alone caused uterine (endometrial CA)- now combo with progestins (Medroxyprogesterone-MPA)
- various regimens now used- estrogen for 25 days with inclusion of MPA during last 10-13 days of estrogen, 5-6 days with no hormones
combo formulas
- PREMPRO (estrone plus MPA) given at fixed daily dose - PREMPHASE (Estrone for 28 days and MPA last 14-28 days)
Newer combos of estrogens with progestins:
- FEM HRT (estradiol plus norethindrone acetate)
- ORTH PREFEST(estradiol plus norgestimate)
- Vaginal creams (PREMARIN) or a ring device (ESTRING): can be used instead of oral doses . Reduces vaginal dryness, yeast infections and urinary tract infections.
CombiPatch (estradiol/norethindrone acetate) transdermal patch
Alcohol free, lasts 3.5 days
Tamoxifen
Selective Estrogen Receptor Modulator (SERM)
Good Effects: reduces breast CA risk, lowers LDL cholesterol, strengthens bones
Bad Effects: Increases uterine CA risk, increases blood clot risk (2-3 fold increase with DVT, PE)
- commonly used as an adjuvant with chemo or radiation in treatment
- preventative agent for women at high risk for breast CA
-* resistance usually develops in 5 years, may reflect alterations in the ER receptors in the tumors
Raloxifene (Evista)
- High affinity for both ER-a and ER-b (antagonist in breast, agonist in bone)
- Treatment of osteoporosis in post-menopausal women
- INVASIVE breast cancer in post-menopausal women (Less effect than tamoxifen against non-invasive)
More effective in women with a uterus than tamoxifen against invasive breast cancer, about the same as tamoxifen in women without a uterus - Does not cause proliferation of the endometrium or breast tumor cells
- No indication for pre-menopausal women, or men
Side effects: 2-3 fold ↑ risk of deep vein thrombosis and pulmonary embolism; Hot flashes (~25%)
Interactions: Ampicillin reduces absorption of raloxifene; Raloxifene reduces warfarin efficacy
Clomiphene
ANTI-ESTROGEN
- Weak agonist and strong antagonist for ER-a or ER-b (partial agonist)
- Oppose the negative feedback effects of endogenous estrogen. ↑amplitude of the LH and FSH pulses
- Major use: induction of ovulation in women with an intact hypothalamic-pituitary-ovarian axis (fertility treatment)
Adverse effects: multiple births, ovarian cysts
HRT Effects of Treatment (Estrogen effects associated tih HRT during menopause
GOOD:
strengthens bones, decreases LDL, increases HDL, reduces menopausal symptoms (hot flashes)
BAD:
increases risk for breast CA & uterine CA (uterine CA risk can be reduced or eliminated by using progesterone with estrogen), increases risk of blood clot (* increased risk of MI/stroke, especially in FIRST YEAR)
- therefore, contraindicated in women with personal/family Hx of CA or CV disease
ICI 182,870 / Fulvestrant (Faslodex)
ANTI-ESTROGEN
- pure estrogen antagonist
- effective in treating tamoxifen-resistant tumors
Progestins - Therapeutic progesterone
Naturally occurring progesterone (low oral bioavailability)
- Micronized particles suspended in oil and packaged in gelatin capsules (PROMETRIUM) - Vaginal gel (CRINONE) - Slow-release intrauterine device (PROGESTASERT)
Mechanism of Action: Interacts with PR to mimic the stimulatory affects of progesterone
Physiological Target: Reproductive Tract
- Decreases estrogen-driven endometrial proliferation
- Establishment and maintenance of pregnancy
Common Uses:
- Oral contraceptives
- HRT to limit estrogen’s effects on the endometrium
- Uterine Bleeding disorders
- Premature labor (decrease uterine contractions)
- Stimulate Appetite in AIDS or cancer patients
Mifepristone (RU 486) (mifeprex)
Anti-progesterone (PR antagonist)
- Used in first trimester to terminate pregnancy(along with prostaglandins to increase uterine contractions)
- Post-coital contraceptive (prevent implantation)
- Investigational: induction of labor after fetal death and treatment of endometriosis.
Adverse Effects: vaginal bleeding, abdominal pain and cramping
Contraindicated in patients with vaginal bleeding, adrenal dysfunction or asthma (due to anti-glucocorticoid actions)
Interactions:
- Decreases efficacy of anticoagulants.
- Inhibits hepatic metabolism by CYP3A4 (eg.anti-retroviral protease inhibitors, calcium-channel blockers, carbamazepine)
Mestranol / Ethinyl Estradiol
Contraception- therapeutic estrogens
- Absorbed efficiently in GI tract. Mestranol is biologically inactive and must be metabolized to ethinyl estradiol. Peak plasma levels within 1 hr after oral administration
- Clearance is ~ 60% 24 hr after oral dose
- Ethinyl estradiol is 2X more potent than mestranol
Norethindrone
Contraception- therapeutic estrogens
19-NOR Steroids : * Progestins
- Removal of 19-carbon changed major hormonal effect from an androgen to progestin while maintaining oral activity
- *Estranes: have some androgenic activity as well as estrogenic/anti-estrogenic actions. Rapidly absorbed (Norethindrone)
Norgestrel, Norgestimate, Desogestrel
Contraception- therapeutic estrogens
- Gonanes (progestins)
- More potent than estranes and less androgenic activity and are now used in the 3rd generation combination oral contraceptives
Monophasic Contraceptive
The concentrations of estrogens and progestins are fixed in the pill, which is taken for 21 days followed by 7 days of “hormone-free” pills.
Estrogen (fixed) + Progestin (fixed)
Biphasic Contraceptive
- Lower concentration in the first 7-10 days and then higher concentration for the next 11-14 days
- The rationale is to limit exposure to the higher concentration of the progestin.
Estrogen (fixed amt) + progestin (2 concentrations)
Triphasic Contraceptive
Fixed concentration of estrogen with 3 different concentrations of progestins
Progestin Only Contraceptives
- Oral formulations of norethindrone (micronor) or levonorgestrel (ovrette) taken daily
- Subdermal implants of levonorgestrel (norplant) for slow-release and long-term contraceptive actions (up to five years)
- IM injections of medroxyprogesterone (depo-provera) that provides effective contraception for 3 months
- IUD that releases low amounts of progesterone locally (progestasert).
Emergency Contraceptives
- Drugs used for the prevention of pregnancy following unprotected intercourse or a known or suspected barrier contraceptive failure.
- Emergency hormone contraceptive regimens are highly effective and decrease the risk of pregnancy by 75 percent
To be effective these must be taken * within 72 hours of intercourse*
- May also inhibit ovulation or fertilization depending on timing of administration
- Alteration of the endometrium, sperm penetration, and tubal motility are also affected (prevent implantation).
ESTABLISHED PREGNANCIES ARE NOT HARMED
Two products are available:
Plan B: 0.75 mg levonorgestrel
Preven: 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol (this product includes a pregnancy test kit)
Extended Regimen Contraception
Levonorgestrel / ethinyl estradiol 0.15 mg / 0.03 mg
And either placebo or ethinyl estradiol tablets 0.01 mg tablets)
Brand Names: Jolessa, Quasense, Seasonale, Seasonique
91-day courses of tablets
Advantages
• Period once every 3 months
• Period last about 3 days with decreased bleeding
Side Effects: Breakthrough bleeding and spotting
Seasonique:
Incorporates low-dose estrogen rather than placebo tablets in an effort to limit bloating, hormonal fluctuations, and breakthrough bleeding.
Benefits of Oral Contraceptives
Initiating Method:
• Start First day of next menstrual period
• Some suggest starting on first Sunday following onset of menses
- Usually avoids menstrual period on weekends
- Most clinicians recommend backup for at least 2 cycles
Other Beneficial effects
- Decreases Dysmenorrhea
- Decreases benign breast and ovarian cysts
- Regulates cycle in anovulatory women
- Decreased blood loss during menstruation
- 50% reduction in ovarian and endometrial cancer.
Oral Cotraceptive- Drug Interactions
Drugs that disrupt liver metabolism and increase
- oral contraceptive metabolism
- anti-seizure medications, St. John’s wort
- antibiotics tetracycline and ampicillin
- HIV protease inhibitors
- Anti-tuberculosis drugs such as rifampin
Oral contraceptives effect the activity of other drugs
- Decrease efficacy of anticoagulants
- Inhibit or increase metabolism of benzodiazepines depending on the drug
- Inhibit metabolism of beta-blockers
- Inhibit metabolism of corticosteroids, and tricyclic antidepressants
Oral Contraceptive Contraindications
- Absolute- KNOW THESE
- History of thromboembolism, MI, stroke
- Impaired liver function
- Known or suspected breast cancer
- Undiagnosed abnormal vaginal bleeding
- Known or suspected pregnancy
- Smokers over age 35 (may use progestin-only)
- Relative
- Migraine headaches
- Hypertension - ok if <35, or healthy, or BP controlled
- Elective surgery: Discontinue 4wks. prior to major surgery
- Gallstones/ Cholecystitis
- Epilepsy: anti-seizure meds may decrease effectiveness of OCP’s
- Diabetes: small risk or worsening vascular disease.
