Hormone Contraception

Question 1

Describe the Mechanism of estrogen and progestin-induced gene transcription.

Answer 1

Both of these hormones will bind two their receptors in the nucleus of a target cell. Binding causes a conformational change leading to the dissociation of deactivating-heat shock proteins. Afterwards, the homodimerized receptors are free to bind DNA or other transcription factors.

Question 2

What are the clinical uses of estrogens?

Answer 2

HRT of primary hypogonadism - given at 11-13 y/o and progestin follows first uterine bleed

Postmenopausal HRT - reduces hot flashes, fractures, and urogenital atrophy

Suppression of ovarian function in hirsutism and acne

Contraception and dysmenorrhea

Question 3

What are the clinical uses of progestins?

Answer 3

Postmenopausal HRT and contraception

Question 4

Describe the MOA of hormonal contraceptives

Answer 4

Prevent ovulation via feedback inhibition of the hypothalamic-pituitary axis.

Note: In combination, progestins and estrogens are more successful at suppression of LH and FSH and ovulation than either alone.

Question 5

Describe the MOA of progestin-only contraceptives

Answer 5

Block ovulation in only 60-80% of cycles

Effectiveness - thickening of cervical mucus and endometrial alterations that impair implantation

Question 6

What are the non-contraceptive benefits of oral contraceptives?

Answer 6

Reduced risk of epithelial ovarian and endometrial carcinoma

Reduced ectopic pregnancy and benign breast disease

Reduced Dysmenorrhea, hirsutism, and acne

Question 7

What are the mild ADRs of oral contraceptives?

Answer 7

Nausea, mastalgia, breakthrough bleeding, edema, and migraines (indication to discontinue)

Question 8

What are the moderate ADRs of oral contraceptives?

Answer 8

Breakthrough bleeding (avoided in combination therapies)

Androgenic effects (avoided with higher estrogen and anti-androgenic progestins)

Question 9

What are the severe ADRs of oral contraceptives?

Answer 9

Vascular disease - thromboembolism (estrogens), myocardial infarction and CVA (elevated risk in smokers)

GI disease - cholestati jaundice and hepatic AD

Depression

Slightly increased risk of breast cancer

Question 10

What are CIs for the use of estrogen-containing contraceptives?

Answer 10

Smokers > 35 y/o
Cardiovascular disease
Migraines
Incomplete epiphysial closure
Estrogen-dependent neoplasms

Question 11

What are the CIs for the use of progestin-only contraceptives?

Answer 11

liver disease and breast cancer

Question 12

Describe the androgenic and estrogenic profiles of progestins

Answer 12

Progestins vary in their estrogenic and androgenic potencies:

More androgenic activity (e.g., L-Norgestrel, Norethindrone) leads to acne, hirsutism, weight gain, etc.

Progestins with lower (Norgestimate) or anti-androgenic (Drospirenone) potency actually treat acne

Question 13

What are the different metabolic effects of L-Norgestrel?

Answer 13

Androgenic, anti-estrogenic, and anabolic

Question 14

What are the different metabolic effects of Norethindrone?

Answer 14

Androgenic, anti-estrogenic, and anabolic

Question 15

What are the different metabolic effects of Drospirenone?

Answer 15

Anti-androgenic

Question 16

Rank the methods of contraception (Oral, transdermal, vaginal ring, injections, IUDs, and implants) with respect to failure rate.

Answer 16

Oral > transdermal > vaginal ring > injections > IUDs > implants

Question 17

Which oral contraceptives allow rapid return to fertility?

Answer 17

Oral, transdermal, vaginal ring, IUDs, and implantations

Note: Injections do not

Question 18

Rank the methods of contraception (Oral, transdermal, vaginal ring, injections, IUDs, and implants) with respect to duration of effectivity.

Answer 18

IUD > Implant > Injection > vaginal ring > transdermal patch, and pills

Question 19

Describe injectable progestin-only contraceptive

Answer 19

Medroxyprogesterone acetate
Injected intramuscularly every 3 months
The return of fertility can be delayed for 6-18 months after the last injection in some patients

Question 20

Describe IUD, progestin-only contraceptive

Answer 20

L-norgestrel

Effective for 5-7 years

Question 21

Describe the implantable progestin-only contraceptive

Answer 21

Etonogestrel
Placed under the skin of the upper arm and is effective for 3 years
Bleeding abnormalities are common

Question 22

Describe the transdermal combo contraceptive

Answer 22

Ethinyl estradiol and norelgestromin
A new patch is applied each week for three weeks, followed by one patch-free week

More frequent breast discomfort, dysmenorrhea, nausea, vomiting, and skin irritation

Question 23

Descibe the vaginal ring combo contraceptive

Answer 23

Ethinyl estradiol and etonogestrel

The ring is inserted and left in place for 3 weeks followed by one ring-free week

Question 24

What are the risks and benefits of estrogen-only HRT?

Answer 24

Decreased osteoporosis

Increased thromboembolism and ischemic stroke

Question 25

What are the risks and benefits of estrogen-progestin HRT?

Answer 25

Decreased osteoporosis and colorectal cancer | Increased breast cancer, MI, thromboembolism, and CVA

Question 26

What is the MOA of tamoxifen and toremifene?

Answer 26

Partial competitive agonist inhibitor of ER

Question 27

What are the uses of tamoxife and toremifene?

Answer 27

ER (+) breast cancer and chemoprevention of breast cancer

Question 28

What are the risks and benefits of tamoxifen and toremifene?

Answer 28

Reduced risk of osteoporosis and atherosclerosis | Slightly increased risk of endometrial cancer

Question 29

What is the MOA of Raloxifene?

Answer 29

Agonistic to ER in lipids and bone | Antagonistic at endometrium and breast

Question 30

What are the clinical uses of raloxifene?

Answer 30

Prevention of post-menopausal osteoporosis and chemoprevention of breast cancer

Question 31

What is the MOA and use of Mifepristone?

Answer 31

MOA - Progesterone receptor antagonist Use - terminate early pregnancy and emergency contraceptive Note: used with misoprostol (synthetic PGE-1)

Question 32

What is the MOA and use of levonorgestrel

Answer 32

MOA - progesterone receptor agonist; unknown how emergency contraception is implemented Use - Plan B; CAN'T reverse an established pregnancy

Question 33

What is the MOA of Ulipristal Acetate?

Answer 33

MOA - similar to levonorgestrel, but longer duration of efficacy Use - contraception, may interfere with established pregnancy