Female reproduction drugs

Question 1

What is clomiphene citrate used for?

Answer 1

Clomiphene citrate promotes folliculogenesis

Question 2

What is the MoA of clomiphene citrate?

Answer 2

Clomiphene citrate is a hypothalamic estrogen receptor antagonist

Question 3

How does antagonizing hypothalamic estrogen receptors promote folliculogenesis?

Answer 3

Estrogen works via feedback inhibition to reduce FSH levels…FSH causes follicular maturation

Question 4

What side effects are possible with clomiphene citrate?

Answer 4

Hot flashes

Ovarian hyperstimulation syndrome

Question 5

What are menotropins used for?

Answer 5

Menotropins promote ovulation in anovulatory women and production of multiple follicles

Question 6

What are menotropins?

Answer 6

Menotropins are gonadotropins (FSH and LH) purified and concentrated from postmenopausal women’s pee

Question 7

What is usually given in sequence with menotropins? Why?

Answer 7

hCG is given in sequence with menotropins because it helps induce ovulation via LH-like surge

Question 8

What drug is given to induce ovulation in women with polycystic ovarian disease?

Answer 8

Urofolitropin promotes ovulation in polycystic ovarian disease patients

(unless clomiphene citrate worked)

Question 9

What is urofolitropin?

Answer 9

Similar to menotropins…but only FSH; no LH

Question 10

What are follitropin a and b?

Answer 10

Recombinant FSH…induces follicular development

Question 11

What side effects would be expected with follitropin a or b?

Answer 11

Hyperstimulation –> multiple fetuses

Ovarian hyperstimulation syndrome –> shift of vascular fluids to abdominal and thoracic regions

Question 12

What is leuprolide?

Answer 12

Leuprolide is a synthetic GnRH

Question 13

What is leuprolide used for?

Answer 13

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

Question 14

What is seen with leuprolide nonpulsatile administration?

Answer 14

Initially transiently increases FSH and LH…then suppresses them

Question 15

What are cetrorelix and ganirelix?

Answer 15

Cetrorelix and ganirelix are GnRH antagonists

Question 16

What are cetrorelix and ganirelix used for?

Answer 16

Fertility: prevent endogenous LH surge while giving exogenous gonadotropins

Prostate/breast cancer: inhibit steroid production

Benign uterine diseases (fibroids)

Question 17

What is seen with cetrorelix and ganirelix administration?

Answer 17

Decrease in endogenous FSH and LH…NO transient rise (seen with GnRH agonist)

Question 18

What is an orally available 17β estradiol (E2)?

Answer 18

Ethinyl estradiol (has a C-17 addition)

Question 19

What are the metabolic effects of estrogen?

Answer 19

Sodium and water retention

Increases HDL and decreases LDL

Question 20

What are some uses of estrogen?

Answer 20

Oral contraceptives
Hormone replacement therapy
Dysmenorrhea

Question 21

How is estrogen used as an oral contraceptive?

Answer 21

In combination with progestins…interferes with LH surge and ovulation

Question 22

What is given with estrogen for hormone replacement therapy?

Answer 22

Progesterone and estrogen are given for hormone replacement therapy

Question 23

What form of estrogen is given as a transdermal patch, topical gel, or vaginal ring?

Answer 23

Estradiol valerate can be given as a patch, gel, or ring

Question 24

Where is estradiol valerate metabolized? Excreted?

Answer 24

Estradiol valerate is metabolized in the liver

Conjugates are excreted in urine or bile

Question 25

What does circulating estradiol bind to?

Answer 25

SHBG binds to estradiol...estradiol increases synthesis of SHBG

Question 26

What are three Selective Estrogen Receptor Modulators (SERMs)?

Answer 26

Tamoxifen Raloxifene Toremifene

Question 27

Are SERMs estrogen agonists or antagonists?

Answer 27

SERMs are BOTH estrogen agonists and antagonists

Question 28

Where does tamoxifen act as an estrogen antagonist?

Answer 28

Breast | Vasculature

Question 29

Where does tamoxifen act as an estrogen agonist?

Answer 29

Uterus Bone Lipoproteins

Question 30

Can tamoxifen be used in premenopausal women?

Answer 30

Yes...unlike other SERMs/SERDs

Question 31

What is tamoxifen used to treat?

Answer 31

Estrogen positive breast cancer (and infertility)

Question 32

What are some potential side effects of tamoxifen?

Answer 32

``` N/V Skin rashes Hot flashes Thromboembolic events Endometrial cancer ```

Question 33

What are some differences between tamoxifen and raloxifene?

Answer 33

Antagonist sites (R only breast and uterus) Side effects (R only DVT and leg cramps)

Question 34

Where does toremifene work?

Answer 34

Toremifene is an estrogen antagonist in breast

Question 35

What are some potential side effects of toremifene?

Answer 35

Hot flashes Lowers LDL Raises HDL

Question 36

What is fulvestrant?

Answer 36

Fulvestrant is a Selective Estrogen Receptor Down-regulator (SERD)

Question 37

What is the action of fulvestrant?

Answer 37

Fulvestrant is an estrogen antagonist in all tissues

Question 38

What is fulvestrant used for?

Answer 38

Estrogen positive breast cancer treatment

Question 39

Where is fulvestrant excreted?

Answer 39

Feces (it is oxidized and conjugated)

Question 40

What is a major (very broad sense) difference between fulvestrant and the SERMs?

Answer 40

Fulvestrant is given IM | The SERMs discussed are oral

Question 41

What are the potential side effects of fulvestrant?

Answer 41

GI disturbances Hot flashes Thromboembolism

Question 42

What aromatase inhibitors re non-steroidal and reversible?

Answer 42

Anastrozole and letrozole

Question 43

What aromatase inhibitor is steroidal and nonreversible?

Answer 43

Exemestane

Question 44

What are aromatase inhibitors used for?

Answer 44

Estrogen receptor positive cancer in postmenopausal women

Question 45

What side effects are expected with aromatase inhibitors?

Answer 45

Hot flashes | Long-term...unknown

Question 46

What are natural and synthetic progestins used for?

Answer 46

Oral contraceptives Hormone replacement therapy Treatment of dysmenorrhea Luteal support for implantation and pregnancy

Question 47

There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of a progestane?

Answer 47

Medroxyprogesterone

Question 48

There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of an estrane?

Answer 48

Norethindrone

Question 49

There are three types of synthetic progestins; progestanes, estranes, and gonanes. What is an example of a gonane?

Answer 49

Levonorgestrel (more potent)

Question 50

How do progestins work?

Answer 50

Progesterone suppresses ovulation (likely via feedback inhibition of HPO/HPG axes)

Question 51

What are some advantages to using progestins?

Answer 51

Reliable contraception Decrease risk of endometrial and ovarian cancer Decrease incidence of ectopic pregnancy Menses regulation

Question 52

What are some disadvantages to using progestins?

Answer 52

Daily administration No STD protection Increased risk of breast cancer with triphasic oral E & P Other side effects (depression, wt. gain, nausea, HTN, DVT)

Question 53

What are mifepristone and ulipristal acetate?

Answer 53

Mifepristone and ulipristal acetate are progesterone antagonists

Question 54

What is mifepristone used for?

Answer 54

``` Emergency contraceptive (low dose) Termination of early pregnancy w/prostaglandin (higher dose) ```

Question 55

What are some side effects of mifepristone use?

Answer 55

Vomiting, diarrhea, and abdominal pain | Heavy vaginal bleeding

Question 56

What is ulipristal used for?

Answer 56

Emergency contraception

Question 57

How do progesterone antagonists work?

Answer 57

Interferes with or delays ovulation | Also alters endometrium