Pharmacology of Estrogens and Progestins

Question 1

What’s the main difference between tamoxifene and raloxifene?

Answer 1

Tamoxifene can cause endometrial and breast cancers, while raloxifene cannot.

Question 2

What metabolic effects does estrogen have on the liver?

Answer 2

Decreased LDL and increased HDL (cardioprotective)

Question 3

What is MHT?

Answer 3

Menopausal Hormone Therapy

Question 4

Risk of ____________ in women being treated with MHT decreases with supplemental progestin.

Answer 4

endometrial cancer

Question 5

What’s the difference between pharmacologic and physiologic doses of estrogen and progesterone?

Answer 5

Pharmacologic doses are much higher and are used to suppress gonadal hormones. Physiologic doses supplement absent estrogen and act to support end organs.

Question 6

Rising ____________ during the follicular stage stimulates a positive feedback mechanism that increases secretion of ____________.

Answer 6

estradiol; LH

Question 7

The __________ surge triggers ovulation.

Answer 7

gonadotropin

Question 8

How are gonadotropins suppressed during the luteal phase?

Answer 8

Progesterone –stimulated by hCG on the corpus luteum –suppresses LH and FSH.

Question 9

How do androgen antagonists affect the estrogen response element?

Answer 9

They also cause a conformational change, but they do so in a different way than estrogen, thus preventing transcription.

Question 10

How does estrogen lead to thrombosis?

Answer 10

It stimulates the production of factors II, VII, IX, and X (just like how it up-regulates thyroid-binding globulin).

Question 11

There is a reduced _____________ effect if estrogen is given transdermally.

Answer 11

hepatic

Question 12

Estrogen is often used to treat __________________ in post-menopausal women.

Answer 12

vasomotor symptoms (e.g., hot flashes)

Question 13

How can the risk of endometrial cancer be reduced in a patient taking estrogen?

Answer 13

They can switch to progestin for a brief bit each month.

Question 14

Where do SERMs have agonist and antagonist activity?

Answer 14

Agonist in bone and liver (excellent!–mostly, there is also a rise in thromboembolic risk, however) and antagonist at breast and uterus (also excellent!).

Question 15

Estrogen has _______________ bioavailability.

Answer 15

good

Question 16

What other GI/metabolic disorder can estrogens cause?

Answer 16

Cholestatic jaundice

Question 17

Use of hormonal contraceptives is contraindicated in ___________.

Answer 17

women older than 35 who smoke

Question 18

In young women, estrogens are often used to treat ______________.

Answer 18

dysmenorrhea

Question 19

What side effect does levonorgestrel (Plan B) have?

Answer 19

Emesis

Question 20

What drug-drug interaction is most common with oral contraceptives?

Answer 20

Hormonal contraceptives are hepatically metabolized, so co-administration of rifampin or phenytoin (just to use two examples) can reduce contraceptive effect.

Question 21

What does SERM stand for?

Answer 21

Selective Estrogen Receptor Modulator

Question 22

Which SERM raises the risk of endometrial cancer

Answer 22

Tamoxifen

Question 23

How does mifepristone work and what is it used for?

Answer 23

It is a progesterone antagonist that causes the corpus luteum to rupture. It is used for terminating early pregnancies –in conjunction with prostaglandins to stimulate uterine contraction.

Question 24

Other than letrozole, what is another aromatase inhibitor?

Answer 24

Exemestane

Question 25

What does estrogen do to the bone?

Answer 25

It stimulates closure of the epiphyseal plate.

Question 26

Other than by inhibiting osteoclast differentiation, how else does estrogen increase bone strength?

Answer 26

It stimulates the production of osteoprotegerin, which binds and captures RANK-L.

Question 27

Although raloxifen is great because it doesn’t increase risk of endometrial or breast cancer, it lacks one of the main therapeutic benefits of estrogen: ______________.

Answer 27

it cannot treat hot flashes

Question 28

How doe tamoxifen and raloxifen affect clotting factors?

Answer 28

They, like estrogen, increase the concentration of clotting factors so they also predispose women to DVTs.

Question 29

What is the mechanistic utility of medroxyprogesterone?

Answer 29

It does not inhibit the pituitary, so it can help end-organ lack of estrogen without disrupting the normal cycle.

Question 30

The most successful contraceptive method is _______________.

Answer 30

subdermal implants followed by IUDs

Question 31

Oral contraceptives increase the risk of _____________ cancer.

Answer 31

cervical

Question 32

The best progestin to add to a regimen aimed at treating acne is _______________.

Answer 32

desogestrel