Gonadal Hormones Flashcards
inhibin produced by the ovaries/testes inhibits ______
FSH
in females, LH acts on _____ cell and converts ____ to ____ via _____ (enzyme)
LH acts on the thecae called and ↑ desmolase which converts cholesterol to androgens
androgens are converted into estrogen in ______ cells via _____ (enzyme) and the hormone that ↑ the activity of this enzyme is _____
granulosa cells; aromatase; aromatase activity ↑ by FSH
LH in males ↑ desmolase activity in _____ cells
Leydig cells
desmolase in both males and females is stimulated by _____ (hormone) in the _____ or ____ cells
LH in theca (females) and Leydig (males) cells
FSH in males ↑ the activity of what enzyme?
androgen binding protein
what occur in the Sertoli cells in male gonands due to FSH being secreted?
↑ 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
testosterone binding to ABP makes the testosterone more/less lipophilic
less
meatranol is a __________
pro drug that is converted to ethinyl estradiol (synthetic estrogen)
estrogens ↑/ ↓ bone resorption
↓ (increases bone mass and thus is protective against osteoporosis and why it is more likely to get osteoporosis in menopause)
what is the effect of estrogen on lipids?
↑ HDL and ↓ LDL (good effects) but cannot be used to treat CVD
what is the risk of giving estrogen to patients?
↑ risk for thromboembolic events due to
- ↑ hepatic production of factors 2, 7, 9, 10 and fibrinogen
- ↓ antithrombin III activity
estrogen ↑/ ↓ the activity of antithrombin III
↓
what are the effects of estrogen on the vasculature?
NO production
prostacyclin production
↑ NO production
↑ prostacyclin production
how is estrogen metabolized?
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
what are some of the more moderate/severe AE of estrogens?
- ↑ risk for endometrial cancer (offset risk by giving estrogen with progestin)
- ↑ frequency of migraines
- choelstatis/gallbladder isease
- thromboembolism
- depression
what are the SERMs (selective estrogen receptor modulators)
- tamoxifen
- raloxifene
- clomiphene
SERMs bind to ______
estrogen receptors and can have agonist or antagonist effects
________ is a SERM that can be used in the treatment of infertility associated with anovulatory cycles (try this before IVF)
clomiphene
tamoxifen is a _____ (type of estrogen drug). what is its MOA and what is it used for?
SERM
- antagonist in breast tissue and against in non breast tissue (endometrium, liver, bone)
used in prevention AND treatment of hormone responsive breast cancer
______ is a SERM used in the prevention of hormone responsive breast cancer
Raloxifene; (tamoxifen is used for prevention and treatment of hormone responsive breast cancer)
raloxifene is used in the prevention and treatment of ________
osteoporosis in post menopausal women
acts as an agonist in bone (inhibits resorption)
what is the MOA of clomiphene?
antagonist in the hypothalamus and thus inhibits the normal feedback inhibition
_______ is a SERM used in the treatment and prevention of osteoporosis in post menopausal women
raloxifene
_______ is a SERM with a ↑ risk for endometrial cancer
tamoxifen because it is an agonist at the endometrial tissue
and example of an SERD is _______
fulvestrant; causes estrogen receptors to be degraded and down regulated in all tissues
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
first line: tamoxifen (SERM)
now give fulvestrant (SERD)
what are the non steroidal aromatase inhibitors?
- anastrozole
- letrozole
they are competitive, reversible inhibitors
what is the steroidal aromatase inhibitor?
- exemestrane
irreversible inhibitor
what are the main effects of progestins (4)
- 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
which is associated with ↑ risk of endometrial cancer: tamoxifen or raloxifene
tamoxifen
what are some of the major AE of progestins?
- uterine bleeding (even though it is given to treat uterine bleeding)
- weight gain
- ↓ HDL levels (especially in androgens progestins)
- thromboembolic events (extremely rare)
_____ is an anti progestin
mifepristone which is a competitive inhibitor at the progesterone receptor and can be used in combination with misoprostol as an abortifacient
what type of drug is danazol
androgen that also has anti estrogen activity
what are 3 AE of using high dose testosterone
- reduction in testicular size
- hepatic abnormalities
- ↑ aggression
spironolactone is a ______ antagonist
androgen receptor antagonist
what kind of drug is finasteride
5 α reductase inhibitor
spironolactone and _______ are androgen receptor antagonists
flutamide
ketoconazole inhibits ______
steroid synthesis
flutamide is used for the treatment of ______
prostate carcinoma (it is a androgen receptor antagonist)
_______ is one of the main treatments for BPH (benign prostatic hyperplasia) and also male pattern baldness
finasteride (5 α reductase inhibitor)
what are some of the clinical uses of ketoconazole?
- treat non operable Cushing’s syndrome and prostate cancer
non selective inhibitor of adrenal and gonadal steroid synthesis
______ is the form of estrogen in post menopausal
estrone (E1)
______ is the form of estrogen in reproductive years
estradiol (E2)
______ is the form of estrogen in pregnancy
estriol (E3)
