Estrogens and Progesterone

Question 1

List the 3 main types of estrogens in order of their estrogenic effects (potency)

Answer 1

Estradial (E2) > Estrone (E1) > Estriol (E3)

Question 2

Describe how estrogen is made in females

Answer 2

Theca cells are sitmulated by LH to make testosterone, which is then brought to the Granulosa cells and made to estradiol by aromatase enzyme

Question 3

What are the primary roles of activin and inhibin?

Answer 3

Released by gonads.
Work to either activate or inhibit FSH release at the anterior pituitary

Paracrine– work opposite their namesake

They have NO effect on LH

Question 4

List some Clinical Uses of estrogens (ethinyl estradiol, DES, mestradiol)

Answer 4

Hypogonadism or ovarian failure

Menstrual abnormalities

HRT in postmenopausal women

Men with androgen-dependent prostate cancer

Question 5

DES

Adverse Effect

Answer 5

For moms who took DES while they had a baby girl in utero, the daughters have an increased risk of clear cell adenocarcinoma of the vagina

Question 6

Estrogens

Adverse Effects

Answer 6

Increased risk endometrial carcinoma

Bleeding in postmenopaual women

Increased risk of thrombi

Question 7

Estrogens

Contraindications

Answer 7

ER-positive breast cancer
History of DVTs
Pregnancy

Question 8

List the 3 SERMs

Answer 8

Tamoxifen
Clomiphene
Raloxifene

Question 9

Tamoxifen

Indication and MOA

Answer 9

Indication: used in ER positive breast cancer

Antagonist or ER in breast tissue
Agonist or ER in bone and uterus tissue

Question 10

Clomiphene

Indication and MOA

Answer 10

Antagonist of ER at hypothalamus. Used to promote ovulation by blocking estrodiol negative feedback –> increase GnRH release and increase LH/FSH to increase ovulation

Question 11

Raloxifene

Indication and MOA

Answer 11

Agonist of bone ERs.

Antagonist of ERs at uterus and breast.

Question 12

Fulvestrant

MOA

Answer 12

Estrogen Receptor Antagonist

Question 13

Fulvestrant

Indication

Answer 13

Used in ER positive breast cancer

Question 14

List some aromatase inhibitors

Answer 14

Anatrozole

Exemestane

Question 15

Anatrozole

MOA

Answer 15

Competitive, reversible inhibitor of aromatase

Question 16

Exemestane

MOA

Answer 16

Irreversible inhibitor of aromatase

Question 17

Aromatase inhibitors

Indications

Answer 17

ER positive breast cancers (early stage, locally advanced, and metastatic)

Question 18

What are the 3 main types of oral contraceptives?

Answer 18

Progestins only

Combined (progestins and estrogen)

Emergency

Question 19

Progestins

MOA

Answer 19

Alter frequency of GnRH pulsatility and decrease anterior pituitary responsiveness to GnRH

Make cervical mucus thicker, preventing egg and sperm from moving around well

Question 20

What is the classic schedule for oral contraceptives?

Answer 20

21 days on, 7 days of placebo

Question 21

What is the basic goal of oral contraceptives?

Answer 21

Suppress GnRH release and LH/FSH surge to prevent ovulation

Question 22

Oral Contraceptives

Contraindications and Side effects

Answer 22

Increased risk thromboembolic events
HTN

Contraindicated in smokers > 35 yo, patients with history of thromboembolism, history of estrogen-dependent tumor

Question 23

Mifepristone (RY-486)

MOA and Indication

Answer 23

Used for abortion (through day 49 of pregnancy)

Competitive inhibition of progesterone at progesterone receptors

Question 24

What are some general symptoms of menopause (estrogen deficiency)?

Answer 24

Early: Vasomotor, insomnia, fatigue, mood change

Intermediate: Urogenital atrophy, urinary incontinence, skin changes

Long term: CV disease, Osteoporosis

Question 25

Relationship between estrogen and endometrial carcinoma

Answer 25

Estrogen therapy increases risk of endometrial carcinoma by 5-8x

Inclusion of progestin may eliminate risk, but this is controversial