Gonadal Hormones

Question 1

inhibin produced by the ovaries/testes inhibits ______

Answer 1

FSH

Question 2

in females, LH acts on _____ cell and converts ____ to ____ via _____ (enzyme)

Answer 2

LH acts on the thecae called and ↑ desmolase which converts cholesterol to androgens

Question 3

androgens are converted into estrogen in ______ cells via _____ (enzyme) and the hormone that ↑ the activity of this enzyme is _____

Answer 3

granulosa cells; aromatase; aromatase activity ↑ by FSH

Question 4

LH in males ↑ desmolase activity in _____ cells

Answer 4

Leydig cells

Question 5

desmolase in both males and females is stimulated by _____ (hormone) in the _____ or ____ cells

Answer 5

LH in theca (females) and Leydig (males) cells

Question 6

FSH in males ↑ the activity of what enzyme?

Answer 6

androgen binding protein

Question 7

what occur in the Sertoli cells in male gonands due to FSH being secreted?

Answer 7

↑ the activity of ABP so you get more testoserone-ABP which ↓ the lipophilicity of the testosterone so that it stays within the seminiferous tubules so that spermatogenesis can occur

Question 8

testosterone binding to ABP makes the testosterone more/less lipophilic

Answer 8

less

Question 9

meatranol is a __________

Answer 9

pro drug that is converted to ethinyl estradiol (synthetic estrogen)

Question 10

estrogens ↑/ ↓ bone resorption

Answer 10

↓ (increases bone mass and thus is protective against osteoporosis and why it is more likely to get osteoporosis in menopause)

Question 11

what is the effect of estrogen on lipids?

Answer 11

↑ HDL and ↓ LDL (good effects) but cannot be used to treat CVD

Question 12

what is the risk of giving estrogen to patients?

Answer 12

↑ risk for thromboembolic events due to

1. ↑ hepatic production of factors 2, 7, 9, 10 and fibrinogen
2. ↓ antithrombin III activity

Question 13

estrogen ↑/ ↓ the activity of antithrombin III

Answer 13

↓

Question 14

what are the effects of estrogen on the vasculature?
NO production
prostacyclin production

Answer 14

↑ NO production

↑ prostacyclin production

Question 15

how is estrogen metabolized?

Answer 15

conjugated by cytochrome enzymes in the liver and then excreted in the bile and hydrolyzed by intestinal bacterial and then reabsorbed as an active drug

Question 16

what are some of the more moderate/severe AE of estrogens?

Answer 16

• ↑ risk for endometrial cancer (offset risk by giving estrogen with progestin)
• ↑ frequency of migraines
• choelstatis/gallbladder isease
• thromboembolism
• depression

Question 17

what are the SERMs (selective estrogen receptor modulators)

Answer 17

• tamoxifen
• raloxifene
• clomiphene

Question 18

SERMs bind to ______

Answer 18

estrogen receptors and can have agonist or antagonist effects

Question 19

________ is a SERM that can be used in the treatment of infertility associated with anovulatory cycles (try this before IVF)

Answer 19

clomiphene

Question 20

tamoxifen is a _____ (type of estrogen drug). what is its MOA and what is it used for?

Answer 20

SERM
- antagonist in breast tissue and against in non breast tissue (endometrium, liver, bone)

used in prevention AND treatment of hormone responsive breast cancer

Question 21

______ is a SERM used in the prevention of hormone responsive breast cancer

Answer 21

Raloxifene; (tamoxifen is used for prevention and treatment of hormone responsive breast cancer)

Question 22

raloxifene is used in the prevention and treatment of ________

Answer 22

osteoporosis in post menopausal women

acts as an agonist in bone (inhibits resorption)

Question 23

what is the MOA of clomiphene?

Answer 23

antagonist in the hypothalamus and thus inhibits the normal feedback inhibition

Question 24

_______ is a SERM used in the treatment and prevention of osteoporosis in post menopausal women

Answer 24

raloxifene

Question 25

_______ is a SERM with a ↑ risk for endometrial cancer

Answer 25

tamoxifen because it is an agonist at the endometrial tissue

Question 26

and example of an SERD is _______

Answer 26

fulvestrant; causes estrogen receptors to be degraded and down regulated in all tissues

Question 27

a patient is found to have hormone receptor positive metastatic breast cancer. the first line treatment of ______ was not useful. What should be given next

Answer 27

first line: tamoxifen (SERM) now give fulvestrant (SERD)

Question 28

what are the non steroidal aromatase inhibitors?

Answer 28

- anastrozole - letrozole they are competitive, reversible inhibitors

Question 29

what is the steroidal aromatase inhibitor?

Answer 29

- exemestrane irreversible inhibitor

Question 30

what are the main effects of progestins (4)

Answer 30

- prevents endometrial hyperplasia by ↓ growth and ↑ vascularization of endometrium - thickening of cervical mucus which inhibits moment of sperm - associated with ↑ in body temp - maintenance of pregnancy

Question 31

which is associated with ↑ risk of endometrial cancer: tamoxifen or raloxifene

Answer 31

tamoxifen

Question 32

what are some of the major AE of progestins?

Answer 32

- uterine bleeding (even though it is given to treat uterine bleeding) - weight gain - ↓ HDL levels (especially in androgens progestins) - thromboembolic events (extremely rare)

Question 33

_____ is an anti progestin

Answer 33

mifepristone which is a competitive inhibitor at the progesterone receptor and can be used in combination with misoprostol as an abortifacient

Question 34

what type of drug is danazol

Answer 34

androgen that also has anti estrogen activity

Question 35

what are 3 AE of using high dose testosterone

Answer 35

- reduction in testicular size - hepatic abnormalities - ↑ aggression

Question 36

spironolactone is a ______ antagonist

Answer 36

androgen receptor antagonist

Question 37

what kind of drug is finasteride

Answer 37

5 α reductase inhibitor

Question 38

spironolactone and _______ are androgen receptor antagonists

Answer 38

flutamide

Question 39

ketoconazole inhibits ______

Answer 39

steroid synthesis

Question 40

flutamide is used for the treatment of ______

Answer 40

prostate carcinoma (it is a androgen receptor antagonist)

Question 41

_______ is one of the main treatments for BPH (benign prostatic hyperplasia) and also male pattern baldness

Answer 41

finasteride (5 α reductase inhibitor)

Question 42

what are some of the clinical uses of ketoconazole?

Answer 42

- treat non operable Cushing's syndrome and prostate cancer non selective inhibitor of adrenal and gonadal steroid synthesis

Question 43

______ is the form of estrogen in post menopausal

Answer 43

estrone (E1)

Question 44

______ is the form of estrogen in reproductive years

Answer 44

estradiol (E2)

Question 45

______ is the form of estrogen in pregnancy

Answer 45

estriol (E3)