Estrogens- produced ovary and placenta, testes, and adrenal cortex.
Progesterone- produced in the adrenal glands, the gonads (specifically after ovulation in the CORPUS LUTEUM), the brain, and during pregnancy the PLACENTA.
-Begins with menstruation (3-6 days)
-Releases gonadotropin-releasing hormone (GnRH) to act on the anterior pituitary which stimulates FSH.
-FSH is released (ant. pit)
-Estrogen secretion dominates and increases.
-Causes endometrium to proliferate
-Stimulates ovulation at midcycle
-Surge of LH started the luteal phase (ant. pit). LH SURGE TRIGGERS OVULATION!!!!!!
-LH surge causes Graffian follicle to swelland rupture resulting in ovulation
-Graffian follicle turns into the corpus luteum
-Preparation of uterus for pregnancy
-Secretes estrogen and progesterone
-If no pregnancy, corpus luteum decreases estrogen and progesterone and you menstrate.
-If pregnancy, placenta secretes human chorionic gonadotropin.
-FSH AND LH ARE HORMONES FROM THE ANTERIOR PITUITARY!!!!!
PHYSIOLOGIC EFFECTS OF ESTROGEN-
-Sensitize myometrium (in uterus) to oxytocin at parturition labor
-Stimulates secondary sex characteristics
-Affect mood andemotions
-Affect body feminine body fat distribution
-Enhances blood coagulation
-Inhibits bone resorption (STRENGTHENS THE BONES)
-Mild mineralocorticoid properties (SALT AND WATER RETENTION)
-Increase HDL (CHOLESTEROL LEVELS DECREASE)
PHYSIOLOGIC EFFECTS OF PROGESTERONE-
-Increase basal body Temperature at ovulation and luteal phase
-Affects emotional state
-Mild mineralcorticoid properties
PHYSIOLOGIC EFFECTS OF TESTOTERONE-
-Development of 2ndary sex characteristics in males
-Growth of larynx, thickening of vocal cords
-Stimulates growth of penis, scrotum, seminal vesicle and prostate gland
-Stimulates and maintains sexual function
-Increases in lean body mass
-Stimulates skeletal growth
-Accelerate epiphyseal closure
-Incrases sebaceous gland activity and sebum production which produces acne
-Incrases erythropoietin in the kidneys
-Decreases HDL cholesterol
-Mild mineralcorticoid properties
ESTROGENS- 2 TYPES-
-Conjugated estrogens (OBTAINED FROM THE URINE OF A PREGNANT MARE (HORSE)
PHARMACOKINETICS OF ESTROGEN-
-Well absorbed from GI tract
-Natural estrogens rapidly metabolized in the liver
-Synthetic estrogens are degraded (metabolized) less rapidly
-Most estrogens are readily absorbed from skin and MM, and vaginally
-Enterohepatic cycling- (ESTROGEN GOES TO LIVER AND IS BROKEN DOWN THEN GOES TO GI AND BACTERIA REACTIVATES ESTROGEN MOLECULES AND THEY ARE REASBSORBED BACK INTO THE SYSTEM)accounts for drug interactions, broad-spectrum antibiotic use alters bowel flora and rend OC ineffective.
-Depends on the sexual maturity of the recipient
-Before puberty- Stimulate development of 2ndary sex characteristics
-Adult female- given cycliacally induce artificial menstrual cycle
-Used for contraception
-MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA
-At or after menopause- prevent s/s of menopause, MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA if patient has an intact uterus.
-Protects against Osteoporosis- but shouldn't be prescribed for this alone use Fosamax.
-THE ONLY TIME ESTROGEN CAN BE GIVEN ALONE IS IF PATIENT HAS NO UTERUS!!!
PHARMACOLOGICAL PREPARATIONS- what it is used for:
-replacement therapy- in men with decreased levels of testosterone.
-edema (NA AND H20 RETENTION)
-changes in libido
-HTN (NA AND H20 RETENTION)
-MONITOR PTS BP FREQUENTLY.
CLINICAL USE OF ESTROGENS-
-Replacement therapy for -
Primary ovarian failure (Turner's syndrome)- Estrogen will stimulate sexual characteristics.
Secondary ovarian failure (menopause) for flushing, vaginal dryness and to preserve bone loss
Male Cancer- decreases the aggressiveness of the cancer.
CONTRAINDICATED IN PREGNANCY, UTERINE FIBROIDS, HEPATIC DISEASE, ENDOMETRIOSIS, THROMBOEMBOLIC DISEASE, AND HYPERCALCEMIA.
-Suppress ovarian function
-Mifepristone-termination of pregnancy
-Cancers- breast, endometrial, and renal.
BIRTH CONTROL PILL NAMES TO RECOGNIZE-
-Estranes- Norethindrone and Norethynodrel
-Gonanes- Levonorgesterol, Desogestrel, and norgestimate.
HORMONE REPLACEMENT THERAPY-
-must be combinationwith progesterone
-giving estrogen alone to women who have not had a hysterectomy increases risk of endometrial cancer
-relieves vasomotor symptoms of meopause such as dizziness, h/a, tachycardia, palpitations, night sweats, atrophic vaginitis
-benefits in Osteoporsis and CV disease
-decreases levels of LDL and lipoproeinemia, increases levels of HDL - PROGESTERONE IS THE OPPOSITE!
TREATMENT FOR HRT-
1. Oral preparations-
-First pass metabolism
-gall bladder disease
-induction of drug-metabolizing enzymes-metabolize other drugs faster..which we don't want...ex. seizure med.
-increased r/f breast cancer-mild
2. Transdermal estradiol preparation-
-physiologic levels of estradiol
-consistent blood levels
-Long duration of action
-Apply 1-2 x per week
-Mild skin reactions
3. Vaginal administration- cream used primarily for vaginal s/s of menopause
4. Vaginal ring- releases estrogen for 3 months- helps atrophic vaginitis and releives menopause s/s
WHY DOES ESTROGEN WORK FOR CONTRACEPTION?
- It stops the pituitary gland from producing LH and FSH which causes a decreased level of estrogen. It also supports the uterine ling to prevent BREAK THROUGH bleeding mid-cycle
TREATMENT FOR HRT-
-cyclic or continuous replacement
-estrogen is for 25 days then progesterone starts on day 10 per cycle
-may or maynot have rx for 5-6 for menses
-progesterone suppresses risk of endometrial hyperplasia and r/f endometrial cancer.
-contain femail hormones
-estrogen and progestin or progestin only
-progestin- long acting subdermal implants and Depot IM injections.
-same amt of progestin and estrogen throughout cycle
-biphasic and triphasic- mimic menstrual cycle- incrased amount after first 1/3 cycle
USE OF CONTRACEPTIVES-
-prevent midcycle FSH/LH surge (big peak)
-Indications- 21 cycle day pilss, start day 5 of menstural cycle or "Sunday start", acne, dysmenorrhea (is a result of increase in uterine prostaglandins which cause ischemia from small arteries in uterus at time of menstration.
-NSAIDS- prohibit prostaglandin synthesis
ADVERSE EFFECTS OF ORAL CONTRACEPTIVES-
-risk of stroke
-smokeer over age 35- do not give!
-caution- in GB disease, thromboembolic disease, and h/o MI or CAD
-contraindicated in active liver disease (where they are metabolized), breast cancer, or CA of reproductive tract
-increased r/f ovarian and endometrial ca
-increased r/f breast ca
S/E OF ORAL CONTRACEPTIVES-
-acne better or worse
-Mastalgia- painful breasts
-migraines better or worse
-no menses- amenorrhea
POSTCOITAL CONTACEPTION RX-
-"The morning after pill- plan B"
-estrogen and progesterone
-not taking other contraceptives!
-taken 72 hours within intercourse
-followed by two doses 12 hours later
-inhibit transport of ova in fallopian tubes and later endometrium to prevent implantation of fertilized ovum
-adverse effects- N/V, h/a, dizziness, leg cramps, abdominal cramps
-comes with a pre-packaged uterine pregnancy test.
ORAL CONTRACEPTIVE DANGEROUS S/E'S-
A- abdominal pain (GB disease)
C- chest pain (MI)
E- eye problems
S- severe leg pain (DVT)
STOP TAKING IF ANY OCCUR!!!!
-drugs which increase heaptic metabolism of OC
-increases possiblitly of contraceptive failure- metabolized out of the system
-Phenytoin, barbituates, carbamazepine, antibiotics alter intestinal flora, warfarin, cyclosporine, anti-depressants, glucosteroids, increased hepatotoxic effects with dantrolene.
PROGESTIN- ONLY CONTRACEPTIVES
-work against egg implantation in the uterus
-blunts LH surge that produces ovulation
-thickens and decreases cervical mucous
-create thin, atrophic endometrium hostile to implantation of blastocyt
-IUD- localized effects on the endometrium
-higher failure rates with progestin-only contraceptives
-increased r/f ectopic pregnancy
-Norethindrone (minipills", Medroxyprogesterone acetate- depo shot, progesterone IUD's- release a small amount locally.
ALL CONTRACEPTIVES SHOULD BE TAKEN?
AT THE SAME TIME EACH DAY TO DECREASE THE R/F BREAK THROUGH BLEEDING.
-Have tissue specific action- work against the estrogen in the body- meds treat infertility.
-med has to bind to estrogen receptors to be effective if blocked can't connect
-FOOL the body into thinking not enough estrogen so FSH and LH are increased to stimulate ovaries for ovulation
-exert tissues-specific antagonist or partial agonist effects
-taken day 5 of cycle- when ovulation occurs
-estrogen agonist and moderate estrogen antagonist
-indications- anovulatory infertility
-antagonizes estrogen receptors in hypothalamic-pituitary-ovarian axis- all of these need to be secreting normally for med to work- can't increase them if they are not functioning normally
-blocks estrogen negative feedback and incrases FSH and LH secretion helps ovarin follicle development and ovulation.
-anovulatory d/o; infertility
-inhibits GnRH by inhibiting neg feedbck effects of endogenous estrogen
-less successful in women with decreased estrogen levels
-unlikely to benefit women with FSH levals at or above 40.
-taken days 5-10 mesntrual cycle
-ovulation expected 5-10 days after last dose of clomiphene
-adverse effects- MULTIPLE BIRTHS
-breast tissue-estrogen receptor antagonist
-TREATS BREAST CANCER
-adverse effects- N/V, hot flashes, vaginal bleeding, menstrual irregularities
-possibly stimulates proliferation of endometrial cells-endometrial CA
-possibly stimulates proliferation of endometrial cells- endometrial CA
-selective estrogen receptor modulator (SERM)
-TREATS OSTEOPOROSIS IN MENOPAUSAL WOMEN.
-but allows estrogen-like effects on bone and lipid metabolims- good for bones
-antagonizes effects of estrogen on breast tissue
-estrogen antagonist in uterine tissue
-an antagonist of progesterone receptors
-sentisizes uterus to action of prostaglandins
-alternative to surgical termination of pregnancy before 9 WEEKS of pregnancy
ANDROGENS- TESTOSTERONE THERAPY-
1. Hypogonadism- primary testicular failure
2. Hypopituitarism- given with growth hormone to obtain maximal effect on skeletal growth. Occassionally used in given in GYN d/o of endometrial bleeding and osteoporosis.
TESTOSTERONE-(MAIN NATURALLY OCURRING ANDROGEN)-
-first-pass metabolism extensive- if taken orally and some is reabsorbed so give IM or TD.
-given parenterally or transdermally
-ONLY ORAL ONE IS METHYLTESTERONE- IF NO OTHER CHOICE- RESISTANT TO HEPATIC METABOLISM BUT CAN CAUSE HEPATIC DAMAGE AND LIVER FAILURE WITH PROLONGED TX.
ANDROGENS- TESTOSTERONE UNWANTED EFFECTS-
-if given for a long period the normal testosterone in your body will lose its effect
-salt and water retention with edema
-CA of liver
-impairs growth in children
-masulinization in girls
-3 x more potent than testosterone
-promote wt gain and muslce development
-what athletes use- ABUSE
-counteract protein metabolism
-treat breast CA
-increase body mass, strength, physical performance