Female reproduction drugs Flashcards
What is clomiphene citrate used for?
Clomiphene citrate promotes folliculogenesis
What is the MoA of clomiphene citrate?
Clomiphene citrate is a hypothalamic estrogen receptor antagonist
How does antagonizing hypothalamic estrogen receptors promote folliculogenesis?
Estrogen works via feedback inhibition to reduce FSH levels…FSH causes follicular maturation
What side effects are possible with clomiphene citrate?
Hot flashes
Ovarian hyperstimulation syndrome
What are menotropins used for?
Menotropins promote ovulation in anovulatory women and production of multiple follicles
What are menotropins?
Menotropins are gonadotropins (FSH and LH) purified and concentrated from postmenopausal women’s pee
What is usually given in sequence with menotropins? Why?
hCG is given in sequence with menotropins because it helps induce ovulation via LH-like surge
What drug is given to induce ovulation in women with polycystic ovarian disease?
Urofolitropin promotes ovulation in polycystic ovarian disease patients
(unless clomiphene citrate worked)
What is urofolitropin?
Similar to menotropins…but only FSH; no LH
What are follitropin a and b?
Recombinant FSH…induces follicular development
What side effects would be expected with follitropin a or b?
Hyperstimulation –> multiple fetuses
Ovarian hyperstimulation syndrome –> shift of vascular fluids to abdominal and thoracic regions
What is leuprolide?
Leuprolide is a synthetic GnRH
What is leuprolide used for?
Shut down HPO and paired with FSH/LH or clomiphene to stimulate follicle production
Reducing symptoms (like bleeding) of uterine fibroids
Controlling hormone dependent prostate and breast cancers
What is seen with leuprolide nonpulsatile administration?
Initially transiently increases FSH and LH…then suppresses them
What are cetrorelix and ganirelix?
Cetrorelix and ganirelix are GnRH antagonists
What are cetrorelix and ganirelix used for?
Fertility: prevent endogenous LH surge while giving exogenous gonadotropins
Prostate/breast cancer: inhibit steroid production
Benign uterine diseases (fibroids)
What is seen with cetrorelix and ganirelix administration?
Decrease in endogenous FSH and LH…NO transient rise (seen with GnRH agonist)
What is an orally available 17β estradiol (E2)?
Ethinyl estradiol (has a C-17 addition)
What are the metabolic effects of estrogen?
Sodium and water retention
Increases HDL and decreases LDL
What are some uses of estrogen?
Oral contraceptives
Hormone replacement therapy
Dysmenorrhea
How is estrogen used as an oral contraceptive?
In combination with progestins…interferes with LH surge and ovulation
What is given with estrogen for hormone replacement therapy?
Progesterone and estrogen are given for hormone replacement therapy
What form of estrogen is given as a transdermal patch, topical gel, or vaginal ring?
Estradiol valerate can be given as a patch, gel, or ring
Where is estradiol valerate metabolized? Excreted?
Estradiol valerate is metabolized in the liver
Conjugates are excreted in urine or bile
What does circulating estradiol bind to?
SHBG binds to estradiol…estradiol increases synthesis of SHBG
What are three Selective Estrogen Receptor Modulators (SERMs)?
Tamoxifen
Raloxifene
Toremifene
Are SERMs estrogen agonists or antagonists?
SERMs are BOTH estrogen agonists and antagonists
Where does tamoxifen act as an estrogen antagonist?
Breast
Vasculature
Where does tamoxifen act as an estrogen agonist?
Uterus
Bone
Lipoproteins
Can tamoxifen be used in premenopausal women?
Yes…unlike other SERMs/SERDs
What is tamoxifen used to treat?
Estrogen positive breast cancer (and infertility)
What are some potential side effects of tamoxifen?
N/V Skin rashes Hot flashes Thromboembolic events Endometrial cancer
What are some differences between tamoxifen and raloxifene?
Antagonist sites (R only breast and uterus)
Side effects (R only DVT and leg cramps)
Where does toremifene work?
Toremifene is an estrogen antagonist in breast
What are some potential side effects of toremifene?
Hot flashes
Lowers LDL
Raises HDL
What is fulvestrant?
Fulvestrant is a Selective Estrogen Receptor Down-regulator (SERD)
What is the action of fulvestrant?
Fulvestrant is an estrogen antagonist in all tissues
What is fulvestrant used for?
Estrogen positive breast cancer treatment
Where is fulvestrant excreted?
Feces (it is oxidized and conjugated)
What is a major (very broad sense) difference between fulvestrant and the SERMs?
Fulvestrant is given IM
The SERMs discussed are oral
What are the potential side effects of fulvestrant?
GI disturbances
Hot flashes
Thromboembolism
What aromatase inhibitors re non-steroidal and reversible?
Anastrozole and letrozole
What aromatase inhibitor is steroidal and nonreversible?
Exemestane
What are aromatase inhibitors used for?
Estrogen receptor positive cancer in postmenopausal women
What side effects are expected with aromatase inhibitors?
Hot flashes
Long-term…unknown
What are natural and synthetic progestins used for?
Oral contraceptives
Hormone replacement therapy
Treatment of dysmenorrhea
Luteal support for implantation and pregnancy
There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of a progestane?
Medroxyprogesterone
There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of an estrane?
Norethindrone
There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of a gonane?
Levonorgestrel (more potent)
How do progestins work?
Progesterone suppresses ovulation (likely via feedback inhibition of HPO/HPG axes)
What are some advantages to using progestins?
Reliable contraception
Decrease risk of endometrial and ovarian cancer
Decrease incidence of ectopic pregnancy
Menses regulation
What are some disadvantages to using progestins?
Daily administration
No STD protection
Increased risk of breast cancer with triphasic oral E & P
Other side effects (depression, wt. gain, nausea, HTN, DVT)
What are mifepristone and ulipristal acetate?
Mifepristone and ulipristal acetate are progesterone antagonists
What is mifepristone used for?
Emergency contraceptive (low dose) Termination of early pregnancy w/prostaglandin (higher dose)
What are some side effects of mifepristone use?
Vomiting, diarrhea, and abdominal pain
Heavy vaginal bleeding
What is ulipristal used for?
Emergency contraception
How do progesterone antagonists work?
Interferes with or delays ovulation
Also alters endometrium
