Estrogens

Question 1

What is estrogen and what does it do?

Answer 1

1. development and maintenance of reproductive tissues
2. regulate CNS
3. effects in peripheral tissues

Question 2

what is progesterone and what does it do?

Answer 2

1. development and maintenance of reproductive tissues
2. maintenance of pregnancy
3. effects in other tissues

Question 3

what is the change in estrogen/ progesterone levels during the early follicular phase?

Answer 3

estrogen suppresses the production of FSH

Question 4

what is the change in estrogen/ progesterone levels during the late follicular phase?

Answer 4

estrogen stimulates the surge of LH & FSH –> ovulation and formation of corpus luteum

Question 5

what is the change in estrogen/ progesterone levels during the luteal phase?

Answer 5

estrogen and progesterone suppress production of LH and FSH

Question 6

describe the regulation of estrogen synthesis?

Answer 6

Question 7

list the physiological effects of estrogen?

Answer 7

1. female maturation
2. endometrial effects
3. metabolic and cardiovascular effects
4. blood coagulation
5. CNS

Question 8

what effects go with female maturation?

Answer 8

1. development in vagina
2. stromal development and duct growth in breast
3. accelerated growth phase
4. growth of pubic and armpit hair
5. alteration in body fat
6. pigment in places

Question 9

what effects go with endometrial effects?

Answer 9

1. development of lining in menstrual cycle
2. prolonged exposure leads to hyperplasia of endometrium and abnormal bleeding

Question 10

what is the consequence of enterohepatic recirculation in estrogen metabolism?

Answer 10

if orally administered there can be hepatic and peripheral adverse effects due to reabsorption back into the liver thats why we use other routes to avoid this

Question 11

what are the clinical uses for estrogens?

Answer 11

hormone replacement therapy, osteoporosis, and hormonal contraception, replacement therapy for hypogonadism

Question 12

why do we use estrogen for hormone replacement therapy?

Answer 12

1. relief in CNS (hot flashes, sweating, flushing)
2. relief in atrophy ( vag dryness, inc. risk of infections)
3. physiological effects ( mood swings, insomnia, depression, nervous)

Question 13

why do we use estrogens for osteoporosis?

Answer 13

1. post menopausal women only
2. dec. reabsorption rate of bone

Question 14

why do we use estrogen in people with hypogonadism?

Answer 14

1. failure of development of ovaries
2. chromosomal disorders
3. castration

Question 15

what are the adverse effects of estrogens?

Answer 15

uterine bleeding, endometrial carcinoma, breast cancer, nausea, headache, weight gain, and fluid retention

Question 16

tell me why estrogen causes uterine bleeding?

Answer 16

1. major cause for post menopausal bleeding
2. endometrial hyperplasia
3. can be prevented by admin of progestin in each cycle

Question 17

tell me why estrogen causes breast cancer?

Answer 17

1. long term use
2. can promote growth if hormones aren’t normal –> additional progestin

Question 18

tell me why estrogen has an effect of endometrial carcinoma?

Answer 18

concomitant use of progestin reduces the risk
1. if given more than normal can result in hyperplasia

Question 19

what is the mechanism of action for SERMs?

Answer 19

1. designer estrogen; partial agonist
2. if the ligand binding is bound with an agonist then helix 12 will allow confirmation and coactivator binding
3. has estrogenic and antiestrogenic effects

Question 20

what is the mechanism of action for antagonists?

Answer 20

if ligand is a SERM modulator bound then helix 12 will block coactivator and have antagonist effect

Question 21

what drugs are aromatase inhibitors?

Answer 21

Question 22

what are aromatase inhibitors used for?

Answer 22

1. block biosynthesis of estrogens
2. gynecomastia
3. off label: ovulation induction
4. used in breast cancer if resistant to tamoxifen

Question 23

what drugs are used as SERMs?

Answer 23

1. tamoxifen
2. toremifene
3. ospemifene
4. raloxifene/bazedoxifene
5. clomiphene

Question 24

What is tamoxifen?

Answer 24

1. pro drug and partial agonist
2. antiestrogen actions: breast cancer
3. estrogenic action: osteoporosis, increase blood clots, weak estrogen agonist

Question 25

what is toremifene?

Answer 25

1. similar to tamoxifen structure 2. serm 3. advanced breast cancer

Question 26

what is ospemifene?

Answer 26

1. serm 2. estrogenic effects on vaginal epithelium 3. treat dyspareunia in post-menopausal women

Question 27

what is raloxifene/ bazedoxifene?

Answer 27

1. SERM/ partial agonist 2. estrogenic actions: osteoporosis in postmenopause, dec. LDL, inc. blood clots 3. antoestrogenic actions: dec. breast cancer, doesn't stimulate endometrial cells, may cause hot flashes

Question 28

what is clomiphene?

Answer 28

1. SERM/ partial agonist 2. inc. secretion of FSH and LH by inhibiting negative estradiol feedback 3. stiulate ovulation in women with amenorrhea, oligomenorrhea, and ovulatory dysfunction 4. PCOS

Question 29

what is Fulvestrant?

Answer 29

1. SERD 2. pure estrogen antagonist 3. breast cancer treatment 4. more effective than SERM if tolerance to tamoxifen

Question 30

what do steroidal estrogens look like?

Answer 30

Question 31

what do non-steroidal estrogens look like?

Answer 31

Question 32

what are estrogenic esters?

Answer 32

1. esterification dec. solubility and slow absorption 2. slow absorption (IM) --> prolong action --> less injections 3. examples: --> estradiol valerate and estradiol cypionate

Question 33

what are conjugated esters?

Answer 33

1. collected from pregnant mares urine (premarin) 2. mix of estrogens --> 50-60% (estrone sulfate) --> other (equilin sulfate)

Question 34

what is 17a- alkylated estrogens?

Answer 34

1. prevents conversion to estrone--> enhance bioavailability and inc. half life 2. 3-alkylated ether is dealkylated quickly in vivo 3. examples: -- mestranol, quinestrol, ethinyl estradiol

Question 35

what happens if there is no pregnancy in the menstrual cycle?

Answer 35

1. corpus luteum degenerates 2. production of estrogen and progesterone by corpus luteum declines --> menstruation

Question 36

what happens if you become pregnant in the menstrual cycle?

Answer 36

1. fertilized egg secretes hCG 2. hCG act like LH to stimulate corpus luteum to produce progesterone in 1st trimester 3. assays can be used to test hCG for pregnancy tests

Question 37

what are the metabolic and cardiovascular effects of estrogen?

Answer 37

1. dec. in rate of reabsorption to bone 2. stimulate transcortin and SHBG 3. alteration in plasma levels ( inc. HDL, dec. LDL)