NURS 301 Revision notes on estrogen.pdf

estrogen

has roles in both males and females. Males - growth spurt, skeletal maturation,

epiphyseal closure, and maturation of sperm. Females - development of female sex

organs and secondary sex characteristics, regulation of menstrual cycle, and skeletal

maturation. Most prevalent forms of this are estradiol and estrone. Both are produced

and secreted by ovaries, although estrone is also made in adrenal glands and other

organs.

estrogen effects

in reproductive tissues: growth of vaginal epithelium, ovarian follicle, mammary gland,

sperm transport, growth of endometrium. In non-reproductive tissues: lowers plasma

releases estrogen which exerts a positive feedback to the hypothalamus, leading to

more GnRH released, more FSH, and continued follicle development. 5. Estrogen has a

simultaneous negative influence on the pituitary, however, inhibiting FSH secretion. 6.

Eventually, the circulating estrogen levels reach a critical threshold concentration and a

large amount of GnRH is released from hypothalamus. 7. This leads to burst of LH from

pituitary. 7. Surge in LH causes the now mature follicle to rupture and release the egg.

8. The follicle secretes progesterone that negatively regulates GnRH, LH, and FSH.

therapeutic estrogens

indications - primary hypogonadism, postmenopausal hormonal therapy, oral

contraceptives, suppress ovulation in patients with intractable dysmenorrhea or

hirsutism, and fetility treatments. Includes estradiol, ethinyl-estradiol, and estrone.

estradiol

main estrogen in premenopausal women. Poor oral bioavailability. Effective as a patch

(estraderm, estrogel). Intramuscular delivery sustains release for weeks (depo

estradiol). Topical administration with vaginal cream (estring).

ethinyl-estradiol

semi-synthetic therapeutic estrogen. Commonly used on oral contraceptives.

complications, endometrial carcinoma, breast carcinoma, and hypertension. In men may

cause feminization of genitalia and impotence. Contraindicated in pregnancy,

incomplete bone growth, undiagnosed genital bleeding, stroke, thrombophlebitis, or

thromboembolic disease, and heart disease. Also shouldn't give to women with BRCA

gene. Decrease efficacy of oral anticoagulants and hypoglycemic agents. Increase

adverse effects of tricyclic antidepressants. Increase the effects of oxytocin on the

uterus. St. John's wort may cause loss of contraceptive or hormonal-replacement

efficacy of estrogens.

hormone replacement therapy (HRT)

good effects during menopause include strengthens bones, lowers LDL cholesterol,

raises HDL cholesterol, reduces menopausal symptoms (like hot flashes). Bad effects

include increases breast cancer risk, increases uterine cancer risk, increases blood clot

risk, increases risk of MI and stroke, especially in the first year. Increased risk of uterine

cancer can be reduced or eliminated by using progesterone alone with estrogen. May

cause higher rate of death.

HRT formulations

May include vaginal creams (premarin) or ring device (estring). THose are used instead

of oral doses. Reduces vaginal dryness, yeast infections, and urinary tract infections.

Combipatch transdermal patch (estradiol/norethindrone acetate) - alcohol free and lasts

3.5 days.

selective estrogen receptor modulators (SERMs)

selectivity is possible because estrogen receptors (alpha and/or beta) show differential

tissue expression; conformation dependent binding to DNA and transcription factors;

and tissue dependent responses ranging between pro-estrogenic, particular estrogenic

and anti-estrogenic effects.

tamoxifen

type of SERM for breast cancer. It is most effective in treatment of tumors that are

estrogen-receptor positive or ER and PR positive. Responses of ER negative tumors is

less than 10%. Adjuvant therapy with chemo or radiation in treatment. Preventative

agent for women at high risk for breast cancer. Resistance usually developed in 5 years

which may, in part, reflect alterations in the ER receptors in the tumors.

raloxifene (Evista)

a type of SERM. High affinity for both ER alpha and beta. Acts as antagonist in breast

Hot flashes in 25%. Ampicillin reduces the absorption of this drug and this drug reduces

warfarin efficacy.

clomiphene

anti-estrogen; weak agonist and strong antagonist for ER alpha or ER beta. Oppose the

negative feedback effects of endogenous estrogen. Increase amplitude of the LH and

FSH pulses. Major use is for induction of ovulation in women with an intact

hypothalamic-pituitary-ovarian axis. Adverse effects for multiple births and ovarian

cysts.

ICI 182,870 Fulvestrant

this is a pure estrogen antagonist. Effective in treating tamoxifen-resistant tumors.

progestins

naturally occuring progesterone with low oral bioavailability. Includes micronized

particles suspended in oil and packaged in gelatin capsules (prometrium), vaginal gel

(crinone), and slow-release intrauterine devise (progestasert). Interacts with PR

(receptor) to mimic the stimulatory affects of progesterone. Targets reproductive tract -

decreases estrogen-driven endometrial proliferation, establishment and maintenance of

implantation). Investigational: induction of labor after fetal death and treatment of

endometriosis. Adverse effects include vaginal bleeding, abdominal pain and cramping.

Contraindicated in patients with vaginal bleeding, adrenal dysfunction or asthma (due to

anti-glucocorticoid action). Interactions: decreases efficacy of anticoagulants. Inhibits

hepatic metabolism by CYP3A4 (Anti retroviral protease inhibitors, calcium channel

blockers, carbamazepine).

oral contraceptives and GnRH analogs

these block contraception at the hypothalamus and pituitary.

tubal ligation

this blocks contraception at the fallopian tube.

IUD and progestin only contraceptive

these block contraception at the uterus.

barrier methods and natural family planning

these block contraception at the cervix and vagina.

estrogens as contraception

include mestranol and ethinyl estradiol. Absorbed efficient in the GI tract. Mestranol is

biologically inactive and must be metabolized into ethinyl estradiol. Peak plasma levels

effect from an androgen to progestin while maintaining oral activity. Include estranes.

estranes

19-NOR steroids that have some androgenic activity as well as estrogenic/anti-

estrogenic actions. Rapidly absorbed. Have norethindrone.

gonanes

therapeutic estrogen for contraception; more potent than estranes and less adrogenic

activity and are now used in 3rd generation combination oral contraceptives. Include

norgestrel, norgestimate, and desogestrel.

therapeutic estrogen and progestin combos

(for contraception) include 1st generation (products containing mestranol), low dose oral

contraceptives (products containing less than 50 mcg of ethinyl estradiol), 2nd

generation low dose (products with gonanes, norethindrone, and low doses of ethinyl

estradiol), and 3rd generation (desogestrel or gestrodene which are progestins with low

dose ethinyl estradiol OR drospirenone with low dose ethinyl estradiol.

monophasic formulation (for contraception)

triphasic formulation (for contraception)

fixed concentration of ethinyl estradiol with 3 different concentrations of noethindrone or

gonanes OR fixed concentration of ethinyl estradiol with three concentrations of

gonanes.

progestin only formulation for contraception

oral formulations of norethindrone (micronor) or levonorgestrel (orvette) taken daily.

Subdermal implants of levonorgestrel (norplant) for slow-release and long-term

contraceptive actions (up to 5 years). IM injections of medoxyprogesterone (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. Established pregnancies are not

Include 90-day course tablets (period once every 3 months, period last about 3 days

with decreased bleeding) but have side effects of breakthrough bleeding and spotting.

seasonique

extended regimen contraception; incorporates low-dose estrogen rather than placebo

tablets in an effort to limit bloating, hormonal fluctuations, and breakthrough bleeding.

intiating method

includes starting oral contraceptives on 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 uses for oral contraceptives

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.

drugs that disrupt liver metabolism and increase oral contraceptive metabolism

include anti-seizure medications, St. John's wort, antibiotics tetracyclin and ampicillin,

HIV protease inhibitors, anti-tuberculosis drugs such as rifampin.

suspected breast cancer, undiagnosed abnormal vaginal bleeding, known or suspected

pregnancy, smokers over age 35 (may use progestin-only)

relative contraindications for oral contraceptives

if there are migraine headaches, hypertension (ok if under 35 or healthy or controlled),

elective surgery (must be discontinued 4 weeks prior), gallstones/cholecystitis, epilepsy

(anti-seizure meds will decrease effectiveness), diabetes (these drugs will worsen

vascular disease).