Fertility and Contraception Flashcards
What are the effects of high concentrations of progesterone on the endometrium during pregnancy?
Progesterone hyperpolarizes uterine smooth muscle membranes makign muscle non-excitable and prevents release of arachidonic acid (so prostaglandins are low)
How does the levles of progesteron changes as parturition approaches?
Estrogen levels rise compared to progesterone causing an increase in prostaglandin release that increases the number of gap junctions that electrically excite myometrial cells
What are some oxytocics?
Oxytocin (Pitocin)
What are the uses of oxytocics?
These can be used to induc labor in case of premature rupture of membranes, fetal growth restriction, uteroplacental insufficiency, pre/eclampsiathese can also be used to control postpartum uterine hemorrhage, induction of uterine contraction after C-section or during uterine surgery, or for induction of therapeutic abortion
What is the use of tocolytics?
delay or prevent premature parturition for brief periods to allow time for additional therapeutic measures including glucocorticoid therapy to increase pulmonary surfactant levels
What are some estrogen therapyoptions?
-Ethinyl estradiol (Estinyl)-Mestranol-Estrogen esters (Delestrogen, Valergen, Depo-estradiol Cypionate)
What are some progestintherapyoptions?
-Norethindrone-Norgestrel-Levonorgestrel
What are some selective estrogen receptor modulators?
Tamoxifene and Raloxifene
What are some antiprogestins?
Mifepristone and Onapristone
What are some aromatase inhibitors?
Anastrozole and Letrozole
What are some testosterone analogs?
Testosterone (systemic or transdermal patches)MethyltestosteroneTestosterone propionate/cypionateDanazol
What are some androgen receptor antagonists?
Flutamide and Bicalutamide
What are some 5a-reductase inhibitors?
Finasteride
Commercial pregnancy diagnostic kits depend on what?
qualitative detection of CG in urine of pregnant women (based on the use of AB specific for the CG unique B subunit)
The exact time of ovulation can be predicted by what?
measuring urinary LH- ovulation occurs 36 hrs after onset of LH surge
How does estrogen act?
Estrogen acts through cytoplasmic receptors, ERa and ERb, that translocate to the nucleus to initiate DNA transcription
Where are ERa receptors located?
in the female reproductive tract (uterus, vagina, and ovary)
Where are ERbreceptors located?
prostate and ovary
How does estrogen affect HDL levels? LDL? TAGs?
Increase HDL and TAG levels and lower LDL cholesterol
How does estrogen affect bone?
It is osteo-protective, hastens bone maturation, and quickens closure of epiphyseal plates in long bones more effectively than testosterone (thus women are shorter than men!)
How does estrogen affect the myometrium?
Increases muscle content (and causes prolfieration of the endometrium during the follicular phase of the menstrual cycle)
T or F. Estrogen increases the production of clotting factors
T. So oral contraceptives and post-menopausal estrogen promote a pro-thrombotic state
How do defective estrogen receptors affect bone in males?
These men suffer from osteoporosis, unfused epiphyses, and increased bone turnover and delayed bone age
How does progesterone affect cholesterol?
decreases HDL and stimulates LDL
Why are native, exogenous estrogens not a good option for hormone therapy?
Estrogens are rapidly degraded by the liver (high first-pass effect), so they are not very effective when given orally.Synthetic estrogens, such as ethinyl estradiol (Estinyl) and mestranol have ethinyl groups which decrease hepatic metabolism
What are the benefits of long-acting esters of estradiol?
These are converted to estradiol in the body (typically administered by IM) (e..g estradiol cpionate)
How does the continuous administration of estrogen (especially in combo with a progestin) affect the pituitary?
it inhibits secretion of gonadotropins
What are some potential AEs of giving estrogen to young girls?
It can cause premature closure of the epiphyses and result in short stature
When used as HRT, estrogen increases the risk of _____
endometrial cancer. This effect is prevented by combining the estrogen with a progestinsmall increase risk of breast cancer and CV events (MI, stroke)
What are the dose-dependent AEs of estrogen therapy?
Nausea, DVT, gallbladder disease,hyperTAGemia and HTN
AEs of Diethylstillbestrol?
infertility, ectopic pregnancy, and vaginal clear cell adenocarcinoma
High doses of progestins cause what?
suppresion of gonadotropin secretion, often causing anovulation in women (thus can be used for birth control, either alone or with estrogen)
What are the toxicities of progestins/?
Low but they may increase BP and decrease HDL. Long-term use of high doses in premenopausal women is associated with a reversible decrease in bone density (a secondary effect of ovarian suppression and decreased ovarian production of estrogen) and delayed resumption of ovulation after termination of therapy
What do hormonal contraceptives consist of?
either a combo or an estrogen and a progestin or a progestin alone
What are some preparations of hormonal contraceptives?
oral pills, long-acting injections, subQ implants, transdermal patches, vaginal rings, and itrauterine devices (IUDs)
What are the three-types of oral contraceptives for women?
-combo progestin/estrogen tablets that are taken in constant dosage throughout the menstrual cycle (aka monophasic)-combo preps that change doses throughout the month-progestin only preps
T or F. The increased risk of TE events incurred by combined hormonal contraceptives and estrogen therapy is usually less than that imposed by pregnancy
T.
What are the AEs of low-dose combined oral and progestin-only contraceptives?
significant breakthrough bleeding, especially during the first few months of therapyNausea, breast tenderness, HA, skin pigmentation, and depression
What is Tamoxifen?
A SERM (mixed estrogen agonists that have agonizing effects in some tissues and acts as partial agonists or antagonists of estrogen in others) that is effective in tx of hormone-responsive breast cancer, where it acts as an antagonistto prevent receptor activation by endogenous estrogens (prophylactic use of tamoxifen reduces the incidence of breast cancer in high-risk women)
Why would tamoxifen increase the risk of endometrial cancer?
It is an agonist of endometrial estrogen receptors, thus promoting endometrial hyperplasia
What are the AEs of Tamoxifen?
hot flashes (antagonist action) and increases the risk of venous thrombosis (agonist action)
How does Tamoxifen affect bone health?
It has more agonist effect and is thus protective to preventing osteoporosis in post-menopausal women
How is Raloxifene differenet from Tamoxifen?
Similar to Tamoxifen, it can help prevent osteoporosis in postmenopausal women adncan reduce the risk of breast cancer in high-risk women via estrogen receptor antagonization, but has no estrogenic effects on endometrial tissue (thus no increased risk of endometrial cancer)AEs are similar to Tamoxifen
What is Clomiphene?
A nonsteroidal SERM compound with tissue-selective actions that is primarily used to induce ovulation in anovulatory women who wish to become pregnant. By selectively blocking estrogen receptors in the pitutitary, clomiphene reduces negative feedback and increased FSH and LH output to stimulate ovulation
What is Fulvestrant?
A pure estrogen receptor antagonist (all tissues) used in the tx of women with breast cancer that is resistant to tamoxifen
What are the main uses of aromataseinhibitors like Anastrozole and Exemestane?
these are competivite inhibitors used in breast cancer tx
T or F. The continuous admin of GnRH agonists like leuprolidesuppresses gonadatropin secretion and thus lowers FSH and LH levels
T.
What are some uses of GnRH agonists?
-precocious puberty-short term tx of endometriosis and uterine fibroids in women
Treatment beyond 6 mo in premenopausal women can result in what?
decreased bone density
What is Mifepristone?
A PO steroid antagonist of progesterone and glucocorticoids used to promote abortion in early pregnancy
T or F. orally given testosterone has little effect
T. Extensive hepatic metabolism
T or F. All so-called anabolic steroids (i.e. ones with the intended effects of anabolism but not adrogen effects) have full androgenic effects when used in humans
T.
What is the primary use of androgen therapy?
hypogonadism. Andorgens have also been used to stimulate RBC production in certain anemias and to promote weight gain in pts. ith wasting syndrome (AIDS)
How can high doses of androgen therapy affect the liver?
can cause jaundice, elevated LFTs, and possible hepatocellular carcinoma
What are Flutamide, Bicaulutamide, and Nilutamide?
nonsteroidal competitive antagonists of androgen receptors primarily used in prostate cancer tx
What is a diuretic with anti-androgen effects commonly used to treat hirsutism in women?
Spironolactone
Why would finasteride and dutasteride be unlikely to cause impotence, infertility, and loss of libido?
because it doesnt affect testosterone levels, only DHT
How else can testosterone production be limited?
continuous admin of aGnRH agonist
Why would combined hormonal contraceptives be used in women with androgen-induced hirsutism?
The estrogen in the contraceptive acts in the liver to increase production og SSBG, which in turns reduces the conc of free androgen
