Female Reproductive Pharmacology Flashcards
For women who have hypohtalamic anovulatory function, what should you give with daily injections?
FSH and LH
What will injections of FSH and LH on days 2-3 of menstrual cycle do in normal ovulatory women?
superovulation
For women with endogenous estrogen activity and normal hypothalamic pituitary-ovarian junction, you can use what drug to antagonist estrogen in order to induce FSH secretion?
clomiphene citrate
In all these cases, what do you give IM or SC when the follicle reaches 1.8-2.0 cm?
hCG
and sometimes progesterone
What are the two drugs that are urinary derived human gonadotropins pooled from postmenopausal women, concentrate and purified?
menotropin (both FSH and LH)
urofolitropin (FSH activity)
Who gets menotropin?
anovulatory women
Who gets urofolitropin?
women with polycystic ovarian disease
Recombinant human gonadotrpoins are also available - what are they?
follitropin A
follitropin B
What are the main gonadotropin stimulator side effects?
- hyperstimulation with multiple fetuses
ovarian hyperstimulation syndrome
Describe ovarian hyperstimulation syndrome
shift of vascular fluids to abdominal and thoracic cavities
usually mild symptoms, but occasionally severe.
What is clomiphene citrate
estrogen antagonist in hypothalamus
a SERM - nonsetoirdal selecive estrogen receptor modulator
What does climiphene citrate stimulate then?
release of GnRH and gonadotropins
It’s used as a fertility drug - about what percentage of patients will ovulate and what percentage will become pregnany?
80% of anovulatory women will ovulate
35% will become pregnant
What are the toxicities for clomiphene citrate?
hot flashes
ovarian hyperstimulatory syndrome
What is the 2-step ovulation induction?
- follicular stimulation using FSH, FSH and LH or clomiphene
- folow with hCG to stimulate the LH surge
WHat is the name of recombinant hCG?
choriogonadotropin alpha
What does hCG do in this context?
- binds to LH receptor to have LH-like induction of ovulation
- sitmulates estrogen primed follicle to induce meiotic resumption of oocytes
What is the synthetic GnRH we should know?
Leuprolide
Leuprolide given in nonpulsatile administration leads to what?
suppression of FSH and LH after an initial transient rise
What are the three reasons to give leuprolide?
- to hust down HPO and paired with a FSH/LH or clomiphene to stimulate follicle production
- For reducing symptoms of uterine fibroids (including bleeding)
- For controlling hormone dependent prostate and breast cancers
Pulsatile administration of leuprolide will cause what?
release of FSH and LH - used to induce follicle development
just mimics the normal axis
What are the two GnRH antagonists?
Ganirelix
Cetrorelix
What do Ganirelix and Cetrorelix do to gonadotropin release?
they anatonize GnRH, so they decrease LH/FSH secretion
Why are the GnRH antagonists used in fertility?
they prevent the endogenous LH surge, while promoting folliculogenesis with exogenous gonadotropins (used to suppress the woman’s own system if it’s not working and replace it with synthetic hormones)
Why are GnRH antagonists used in prostate an dbreast cancer?
inhibit steroid production
So if GnRH antagonists and continuous use of the GnRH agonists both cause decreased FSH/LH secreiton, what’s the difference?
you don’t see the transient increase in FSH/LH with the GnRH antagonists
What are the three natural estrogens?
17beta estradiol (E2) - this is prominent
estrone (E1)
estriol (E3)
What are the general effects of estrogen?
development, growth and maintenance of sex accessary tissue
skeletal growth and development of body shape (help the epiphyseal growth plates close - mutation makes you tall)
key regulator of the HPO axis and therefore in maintaining the menstrual cycle
What are the metabolic effects on estrogen?
sodim and water retention
increase in HDL and decreased LDL (heart protective)
What are the main uses of estrogen?
- oral contraceptives (usually with progestins)
2. Hormone replacement therapy
Estradiol 17b is the prinicpal natural hormone, what do we add to reduce metabolism and make orally active in a medication? What is this called?
OH at C17
this is ethinyl estradiol
What are the 4 general routes of admission?
injeciton
transdermal patch
topical gel
vaginal ring
How is ethinl estradiol metaolized?
mby the liver, excreted in kidney or bile
Circulating estradiol is bound to what?
steroid hormone binding globulin
Clomiphene citrate is a SERM. Is it an antagonist or agonist at the level of the hypothalmus
antagonist
What is clomiphene citrate used for?
- ovulatory dysfunction in patients who are not pregnant
- polycystic ovarian syndrome
- amenorrhea
What are the side effects of clomiphene citrate?
nausea, vomiting, skin rashes
hot flashes
thromboembolic events (esp those who smoke)
endometrial cancer
What is Tamoxifen?
also a selective estrogen receptor modulator
Where is tamosifen an anatonist?
breast and vasculature
Where is tamoxifen an agonist? good or bad
uterus (bad - endometriosis)
bone (good - less osteoporotsis)
What additional thing do we use tamoxifen fo?
treatment and prevention so festrogen positive breast cancers
What are two other SERMs?
Raloxifene
Toremifene
Where is Raloxifene an agonist and why is it better than Tamosifen?
agonist in bone and lipoprotein (good), but not in the uterus - which is why it’s sometimes preferred to tamoxifen
WHat is the selective estrogen receptor down regulator?
Fulvestrant
What are the side effects of fulvestrant?
GI disturbances
hot flashes
thromboembolism
How is fulvestrant administered?
IM injection once a month - helpful for compliance
What are the three aromatase inhibitors we know?
anastrozole
letrozole
exemestane
What are the two nonsteroidals? Reversible?
anastrozole
letrozole
are reversible
Which one is a steroid? Reversible?
exemesate is steroidal, not reversible
WHat are the aromatase inhibitors used for?
treat ER+ cancer in postmenopausal women
this is because in postmenopausal women, most estrogen is not made in the ovaries, it’s made by aromatase in the periphery
What are the actions of progesterone?
development and maintenance of secretory endometrium
promotes uterine relaxation during pregnanty - withdrawn during late pregnancy
prepares breast for lactation
What are the receptors for progesterone?
PR-A ad PR-B
What are the main uses for synthetic progestins?
- OCPs
- Hormone replacement
- Treatment of dysmenorrhea
- Luteal support for impoanation and pregnancy
- As plan B to interfere with ovulation
What is the natural progestin?
progesterone C21
What synthesizes progesteron?
Corpus luteum
placenta
testes and adrenal
What are the three progestins we should know for her?
medroxyprogesterone acetate
Norethindrone
Levonorgestrel
Which is the progestane?
medroxyprogesterone acetate
Whish is the estrane?
norethindrone
Which is the gonane?
levonorgestrel
Progestins are absorbed readily, but significantly metabolized in first pass. What will retard this?
17C substitutions
THey are metabolized and conjugated in the liver and excreted ….
by kidney and bile
Progesterone will bind to what in the serum
cortisol binding globulin
How about 19-nor progestins?
steroid hormone binding globulin
What are the two treatment modality for emergency contraception and abortefacient?
progesterone agonist: levonogestrel
Progesterone antagonist: mifepristone and ulpristal acetate
What is the plan B progestin?
levonogestrel
Can plan B terminate a pregnancy?
no - high dose progestin is required to maintain a pregnancy
What is Ella?
ulipristal - efficacy upt o 5 days
What is mifepristone?
it’s a weak anti-progesterone; a 19-nortestosterone analog which is used as emergency contraception or abortifacent
