Estrogen and Progesterone

Question 1

Which estrogen in the major circulating one in pre-menopausal women?

Answer 1

17-beta-estradiol (E2)

Question 2

Which estrogen is the main one in post-menopausal women? And where is it produced in the body?

Answer 2

Estrone (E1); produced in the adipose tissue from adrenal androgens

Question 3

What is the metabolic product of estrone and estradiol?

Answer 3

Estriol

Question 4

In response to which hormone, does follicular cells decrease production of estradiol and begin producing progesterone?

Answer 4

Luteinizing Hormone

Question 5

Which hormones does the corpus luteum produce?

Answer 5

Estradiol and progesterone

Question 6

Which hormone can cause endometrial hyperplasia and increase risk of endometrial cancer?

Answer 6

Estrogen

Question 7

What is the effect of estrogen on bones?

Answer 7

Maintain density by decreasing resorption; promote closure of epiphyses (termination of bone growth)

Question 8

What is the effect of estrogen on cardiovascular system?

Answer 8

Increases HDL and decreases LDL; increase blood coagulation through enhanced hepatic production of clotting factors

Question 9

What is the mechanism of estrogen action?

Answer 9

• binding to nuclear receptors (inactive form)
• binding causes dissociation of co-repressor, dimerization of receptor, and binding to ERE (estrogen response elements)
• coactivators recruited and transcription and protein synthesis follows

Question 10

Definition of menopause

Answer 10

cessation for 12 months

Question 11

Define perimenopause

Answer 11

period before menopause which symptoms such as hot flashes and night sweats first begin

Question 12

What were the findings of Womens’ Health Initiative?

Answer 12

E+P or E alone increased risk of CV disease and decreased risk of fracture in post-menopausal women

Question 13

What risks are associated with HRT therapy in post-menopausal women?

Answer 13

CHD; venous thromboembolism; non-fatal stroke; breast cancer (but not E alone); Endometrial cancer (if used E alone); gall bladder disease; cognitive decline and dementia

Question 14

What is Premarin?

Answer 14

Conjugated equine estrogens: mix of estrogens but mainly estrone

Question 15

What are the benefits of transdermal route administration of estrogen?

Answer 15

Avoids first pass metabolism so you’re not getting as much effects of clotting factors. This lowers risk of VTE.

Question 16

What is Estring?

Answer 16

Vaginal ring containing 17-beta-estradiol which is sustained release for 90 days.

Question 17

What is vagifem?

Answer 17

Estradiol hemihydrate tablets inserted vaginally daily then 2x/week for maintenance.

Question 18

What is the mechanism of SERM?

Answer 18

Selective estrogen receptor modifiers bind to nuclear estrogen receptors and competitively inhibit the binding of estrogen. Can either produce antagonistic effect or agonistic effect depending on tissue.

Question 19

Which drugs are considered SERM?

Answer 19

Tamoxifen, Raloxifene, Clomiphene

Question 20

Tamoxifen is used as first line therapy for breast cancer in pre-menopausal women or post-menopausal women?

Answer 20

Pre-menopausal women. Post-menopausal, it is 2nd line therapy.

Question 21

In which tissue is tamoxifen agonistic and which tissue is it antagonistic?

Answer 21

Agonist in uterus and bone. Antagonist in breast cancer.

Question 22

Tamoxifen is used as adjunct therapy in early stage breast cancer or advanced stage?

Answer 22

Early stage; in adjunct to surgery or chemo

Question 23

In which tissue is raloxifene agonistic and which tissue is it antagonistic?

Answer 23

Agonist at bone and antagonist at uterus and breast

Question 24

Uses of raloxifene?

Answer 24

• Preventing invasive breast cancer in women at high risk

- Post-menopausal osteoporosis (vertebral fracture, not hip)

Question 25

Which SERM increases risk of endometrial cancer?

Answer 25

Tamoxifen

Question 26

What is clomiphene used to treat?

Answer 26

Anovulatory infertility

Question 27

What is the mechanism of action of clomiphene?

Answer 27

Blocks negative feedback of estrogen on hypothalamus and increase pituitary production of gonadotropins.

Question 28

Name the 2 aromatase inhibitors and their type.

Answer 28

Exemestane: Type 1, steroidal, irreversible
Anastrozole: Type 2, non-steroidal, competitive

Question 29

Mechanism of Fulvestant

Answer 29

Binds to ER, competitive inhibition of estrogen, prevents ER dimerization which leads to ER degradation

Question 30

When is fulvestant used?

Answer 30

Treatment of metastatic breast cancer in postmenopausal women who have disease progression following prior endocrine therapy

Question 31

What are the physiological effects of progesterone in pregnancy?

Answer 31

Suppresses menstruation, decrease uterine contractility, role in preparing breasts for lactation

Question 32

Progestins oppose which effects of estrogen?

Answer 32

Endometrium and lipoprotein-cholesterol levels

Question 33

Progestins enhance which effects of estrogen?

Answer 33

Effects on Breast and Bone

Question 34

What effect does progestin have on breast cancer?

Answer 34

Progestin may actually increase risk of breast cancer however in high doses it is used ad adjunct or palliative treatment of breast cancer and endometrial cancer.

Question 35

What is mifepristone?

Answer 35

Competitive inhibitor of progesterone receptors. Can be used as abortion pill, emergency contraceptive, to treat endometriosis

Question 36

What is ulipristal acetate?

Answer 36

Selective progesterone receptor modifier. Partial agonist activity

Question 37

What are the uses of ulipristal acetate?

Answer 37

Treatment of uterine fibroids, emergency contraceptive (not approved in Canada)