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Flashcards in Estrogens & progestins Deck (37):
1

What are the indications for estrogen therapy?

HRT for postmenopausal women
Component of oral contraceptive
Primary hypogonadism (eg Turner)
Primary ovarian insufficiency

2

When would you add a progestin to estrogen therapy? Why?

*If uterus present
- Add a progestin to reduce risk of endometrial cancer

3

Adverse effects of estrogen therapy?

Increased risk of:
Endometrial cancer
Thromboembolic disease
GB disease
Postmenopausal bleeding
Dementia (older pts)
Breast tenderness
Severe migraines

4

What are the contraindications for estrogen therapy?

High risk for or h/o breast cancer
H/o endometrial cancer
H/o thromboembolic disease
H/o genital bleeding
Liver disease
Heavy smoking (stroke risk)

5

Which CYP450 enzyme does estrogen interact w/, and how?

Estrogen metabolized by CYP3A4
- Decreased clinical efficacy in presence of CYP3A4 inducers

6

List the 3 SERMs.
What does SERM stand for?

Tamoxifen, Raloxifen, Clomiphene

Selective estrogen receptor modulator

7

Tamoxifen's MoA?

Raloxifen's MoA?

Clomiphene's MoA?

Tamoxifen: ER antagonist in breast
ER partial agonist–endometrium & bone

Raloxifen: Partial agonist bone (induces ER-dependent bone promoting genes)
ER antagonist in endometrium & breast

Clomiphene: ER antagonist hypothalamus/pituitary: inhibits ER negative feedback and maintains gonadotropin release
ER partial agonist in ovary

8

Indications for tamoxifen, raloxifen, and clomiphene, respectively?

Tamoxifen: Primary prevention of high risk breast cancer
Treatment of advanced breast cancer
Treatment male gynecomastia

Raloxifen: Treatment of osteoporosis in post menopausal women
Alternative to tamoxifen in breast cancer primary prevention (not approved for tx)

Clomiphene: Female infertility due to anovulation (e.g. PCOS)

9

What are the adverse effects of tamoxifen, raloxifen, and clomiphene, respectively.

Tamoxifen: Hot flashes
Increased risk of thromboembolic events
Increased risk of endometrial cancer

Raloxifen: Hot flashes
Increased risk of thromboembolic events
Leg cramps

Clomiphene: Hot flashes
Multiple pregnancies

10

What are the contraindications for tamoxifen, raloxifen, and clomiphene, respectively?

Tamoxifen: H/o thromboembolic events
H/o endometrial cancer

Raloxifen: H/o thromboembolic events
Pregnancy (birth defects)

Clomiphene: none listed

11

What is the name of the drug that is a selective estrogen receptor degrader (SERD)?

What is the MoA?

Fulvestrant

Binds the estrogen receptor and promotes its degradation via the proteosome- inhibits ER signaling

12

When would you use fulvestrant?

Treatment of advanced ER+ metastatic breast cancer, typically following failure of tamoxifen therapy

13

What are the adverse effects of fulvestrant?

Hot flashes
Increased risk of thromboembolic events
Elevated liver enzymes

14

When is fulvestrant contraindicated?

Pregnancy/lactation

15

What are the names of 3 drugs that are aromatase inhibitors?

What is the MoA?

Anastrozole, Letrozole, Exemestane
"Let Ana's Ex" inhibit Aram

Inhibit aromatase -> Prevent the conversion of androgens into estrogens

16

When are the aromatase inhibitors indicated?

Adjuvant therapy of ER+ breast cancer in post menopausal women

17

What are the adverse effects of anastrozole, letrozole, and exemestane?

How are they advantageous compared to tamoxifen?

Symptoms of estrogen deficiency
Increased bone fractures
Unlike tamoxifen does not increase endometrial cancer

18

What are aromatase inhibitors contraindicated?

Premonopausal women (since there is little effect due to increased homeostatic expression of aromatase)

19

Try to name the progestins. (6 we have to know)

Norgestrel
Levongestrel
Norethindrone (only 1 w/o gest in the name)
Desogestrel
Gestodene
Norgestimate

20

What is the MoA of progestins?

Agonists of the PR (some also weakly activate AR). Results in:
(A) Decrease in frequency of GnRH pulses
-> Decreased gonadotropins
-> Decreased ovulation
(B) Thickens cervical mucus
-> impairs sperm penetration
(C ) Reduces endometrial growth and impairs blastocyst implantation

21

When are progestins indicated?

Hormone replacement
Hormone contraception

22

What are the adverse effects of progestins?

Menstrual irregularities
Breast tenderness
Ovarian cysts
Acne

23

What is the MoA of combined oral contraceptive estrogen + progestin?

Estrogen + progestin
-> inhibit GnRH release
-> Inhibit LH + FSH
-> Inhibit follicular development and ovulation

Progestin also:
Promotes thickening of cervical mucus
Reduces endometrial growth

24

What are the indications for combined oral contraceptive estrogen + progestin besides contraception? (4)

What diseases does it decrease risk of?

- Tx of menstrual cycle disorders
- Hyperandrogenism (e.g. acne)
- Bleeding due to fibroids
- Tx of endometriosis

- Decrease risk of endometrial and ovarian cancer

25

What are the adverse effects a/w combined oral contraceptive estrogen + progestin?

Bloating, nausea
Breast tenderness
Breakthrough bleeding
Risk of venous thrombosis
Risk of MI
Increased risk hepatic adenoma

26

When is combined oral contraceptive estrogen + progestin contraindicated?

Age > 35 y & smoking
CAD
H/o venous thrombosis
H/o stroke
Systemic lupus (clotting)

H/o breast cancer
H/o liver disease

27

What are the names of the 2 emergency contraceptives? (which is given at high dose?)

Levonorgestrel (high dose)
Ulipristal

28

What is the MoA for levonorgestrel?

For ulipristal?

Levonorgestrel: Activates PR; Inhibits or delays ovulation by inhibiting the LH surge

Ulipristal: partial agonist of PR- acts as an antagonist in presence of progesterone; Inhibits or delays ovulation by antagonizing PR-dependent genes involved in follicular rupture.
Effective even if given at time of LH surge"

29

What are the indications for levonorgestrel?

For ulipristal?

Levonorgestrel: Prevention of pregnancy
Following unprotected sex or failure of barrier contraception"

Ulipristal: same, but also tx of uterine fibroids

30

What are the adverse effects a/w levonorgestrel?

For ulipristal?

Nausea
Delay of menses
(for both)

31

Which is containdicated during pregnancy: levonorgestrel, ulipristal, both, or neither?

Ulipristal

32

When must you give levonorgestrel for it to be effective as an emergency contraceptive?

Ulipristal?

Levonorgestrel: Only effective if given 1-2 days prior to LH surge.
*Must be given within 72 hrs of intercourse
- Taken once daily for 5 days

Ulipristal: effective when given up to 5 days after sex

33

What types of drugs are mifepristone + misprostol (given together), and what is each of their MoA?

Abortifacient

- PR antagonist, impairs development of endometrium and promotes menses.
- Also Glucocorticoid R and androgen R antagonist
- Misprostol (PGE1 analog) promotes uterine contraction and expulsion of blastocyst

34

When must mifepristone + misprostol be given by?

Before 70 days gestation

35

What are the adverse effects of mifepristone + misprostol?

Excessive vaginal bleeding
Abdominal cramps

36

When are mifepristone + misprostol contraindicated?

Chronic adrenal insufficiency as can precipitate an adrenal crisis
Bleeding disorder or anticoagulants

37

Name the progestin that doesn't have "gest" in it's name.

Norethindrone (AKA norethisterone)