estrogen therapy

Question 1

what cells in the ovary make estrogen?

Answer 1

granulosa cells

Question 2

major estrogen made by granulosa cells is

Answer 2

estradiol-17B (hydroxyl in 17 position)

Question 3

two weak estrogen forms?

Answer 3

estrone

estriol

Question 4

estrogen mechanism

Answer 4

diffuses through membrane
Binds to nuclear estrogen receptors (ER)
causing a conformational change
2 ERs form a homodimer that binds to an estrogen response element and coactivators
complex activates gene transcription

Question 5

at puberty, pulses of _____ stimulate the release of FSH and LH

Answer 5

GnRH

Question 6

effects of GnRH pulses during puberty

Answer 6

• At puberty, pulses of GnRH stimulate the release of FSH and LH
o small increase in estrogen causes breast enlargement and altered fat distribution (female body contour) and growth spurt
o increased clotting factors  increased risk of thromboembolism
o After a year, sufficient estrogen is produced to induce endometrial changes resulting in periodic bleeding

Question 7

menstrual cycle process

Answer 7

o 1 follicle develops under FSH influence (this one has increased expression of FSH receptors; all others regress)
o FSH and LH cause granulosa cells to secrete Estrogen
o Estrogen stimulates endometrium proliferation
o Estrogen peaks and begins to drop just before ovulation
o Now LH and FSH SURGE causing ovulation
o Follicle becomes corpus luteum and cells of it produce Estrogen and progesterone
o Progesterone stimulates glandular endometrium
o If no pregnancy, CL degenerates and menses

Question 8

o Equilin and equilenin

Answer 8

equine estrogens – conjugated with SO4 usually; not absorbed right away due to charge so it avoids 1st pass metabolism by liver and is absorbed in lower intestine

Question 9

oral estrogens

Answer 9

ethinyl estradiol and mestranol
o Not active orally regularly (liver)
Modification in the 17alpha position renders E orally active!

add an ethinyl group to create ethynyl estradiol and additional methyl for mestranol

Question 10

postmenopausal hormone replacement therapy PROs

Answer 10

o Treatment reduces these problems by: decreasing bone absorption, promotes vasodilation, increases vaginal glandular secretion and thickness/elasticity of vagina

Question 11

treatment for postmenopausal osteoporosis

Answer 11

give a bisphosphonate like alendronate
or SERMS (ralofifene or tamoxifen)

Question 12

SERMs

Answer 12

tamoxifen or raloxifene – estrogen agonist by increasing receptors

Question 13

raloxifene

Answer 13

Used for postmenopausal osteoporosis
o E antagonist in breast and sort of on endometrium - decreases breast cancer
o E agonist on bone (osteoporosis protection)
o E agonist on clotting factors (but less than tamoxifen)
o E antagonist in hypothalamus (increases hot flashes)

Question 14

tamoxifen

Answer 14

used to prevent breast cancer
o E antagonist in breast but agonist in endometrium – decreases breast cancer!
o E agonist in Bone (protects against osteoporosis)
o E agonist in increasing clotting factors (risk of thrombosis)
o E antagonist in hypothalamus (increases hot flashes)

Question 15

• Ospemifene

Answer 15

only SERM that is an E agonist on vaginal epithelium  treat dyspareunia in postmenopausal women/reverses vaginal atrophy
o Agonist on bone and endometrium
o Antagonist breast tissue and hypothalamus