Sept10 A1-Hormone Replacement Therapy

Question 1

HRT def

Answer 1

using E and P

Question 2

normal E drop in men and women in life

Answer 2

• women increase mid 20s then big drop at menopause but stays good amount
• men drops slowly throughout life (elderly men more estrogen than elderly women)

Question 3

normal testo drop in men and women in life

Answer 3

-men drops slowly in life and always have much more than
women
-women same slow drop but always much less

Question 4

menopause def

Answer 4

permanent cessation of menstruation resulting from loss of ovarian fct

Question 5

FSH and LH after menopause

Answer 5

high levels bc no P and E

Question 6

why less P and E after menopause

Answer 6

• no more coming from follicles (theca cells and GCs)

- comes fro mother sources

Question 7

source of estradiol and estrone after menopause

Answer 7

estradiol from adrenals

estrone from adipose tissue

Question 8

receptors for estrogen

Answer 8

• nuclear Rs ERalpha and ERbeta. turn on gene expression. diff effect in diff tissues
• GPCRs for E

Question 9

location of estrogen R in the body + most important ones that HRT works on

Answer 9

• brain
• heart
• liver (so E can regulate prot synthesis)
• breast
• uterus
• bone
• HRT especially for osteoporosis and heart disease*

Question 10

ERalpha and beta diff and significance

Answer 10

• sequences are similar but still differ
• diff organs have diff ratio of ER alpha and ERbeta number of Rs.
• can use diff ER agonists or antagonists that bind ERa and ERb with diff ratio to get diff effects

Question 11

Rs for progesterone

Answer 11

• PRa and PRb (nuclear)

- GPCR

Question 12

ERa and ERb vs PRa and PRb

Answer 12

• ERa and ERb = 2 diff genes

- PRa and PRb = 1 gene undergoes alternative splicing

Question 13

Rs for progesterone are where

Answer 13

• CNS
• hypoth
• systemic (metabolism)
• endometrium
• mammary glands

Question 14

name of HRT with estrogen only

Answer 14

not called HRT but called ERT (estrogen replacement therapy)

Question 15

why add P with E to make HRT

Answer 15

give HRT to women with a uterus to avoid increased risk of endometrial cancer than comes from ERT

Question 16

early sx in menopause

Answer 16

don’t last long, short-lived. weeks to months

• hot flashes
• insomnia
• moodiness

Question 17

intermediate sx in menopause

Answer 17

months to years

• vaginal atresia
• bladder dysfunction
• skin atrophy

Question 18

late sx in menopause

Answer 18

years to decades

• osteoporosis
• CVD

Question 19

does HRT work for hot flashes (early sx)

Answer 19

yes

Question 20

does HRT work for vaginal dryness (interm sx)

Answer 20

yes but give as local low dose vaginal cream

Question 21

do phytoestrogens from some vegan food work as an alternative to HRT

Answer 21

maybe, limited evidence. not being tested well

Question 22

osteoporosis (late sx) def

Answer 22

decrease of bone mass density with aging

-is much greater in women due to menopause

Question 23

RFs for osteoporosis

Answer 23

• low Ca diet
• lack of exercise
• high protein diet
• high alcohol use
• smoking
• lack of vitD from sun, diet, pills
• high salt diet
• high caffeine use

Question 24

bone homeostasis

Answer 24

• osteoblasts making bone
• osteoclasts break down bone and remodel it
• E inhibits osteoclastic activity
• at menopause, osteoclastic activity increases bc of E drop

Question 25

what happens when lost bone density and then start taking HRT

Answer 25

you stop losing bone density and your current bone density is maintained

Question 26

alternatives to HRT for osteoporosis

Answer 26

- 1500 mg Ca per day - 800 IU vitD per day - biphosphonates and other meds - act on the risk factors * proven to decrease fractures probability*

Question 27

mech of action of biphosphonates

Answer 27

- incorporate in PO4 and OH of bone matrix - osteoclast eat the BPP while remodelling the matrix - BPP kills the osteoclast that ate it

Question 28

risk of BPP

Answer 28

rare type of femur fracture

Question 29

osteoporosis, if pharmacology therapy is indicated, what are the meds that can be used

Answer 29

- BPP - selective estrogen R modulator - PTH - estrogens - calcitonin

Question 30

SERMs mech of action

Answer 30

- look like E but interact with ERs with diff ratio of ERa and ERb activity (in the nucleus) - change the conformation of ERa and ERb to modify their activity (make them active or inactive depending on tissue)

Question 31

perfect SERM would do what

Answer 31

- strengthen bone - lower LDL cholesterol and raise HDL cholesterol - relieve hot flashes - reduce breast cancer risk - reduce uterine cancer risk

Question 32

one example of SERM

Answer 32

raloxifene - agonist of the Rs in bone and lipids (helps for osteoporosis and CVD risk) - antagonist of the Rs in breast and endometrium (reduce cancer risk)

Question 33

HDL vs LDL

Answer 33

- HDL (high density lipoprotein) is good cholesterol and helps move cholesterol back to the liver for removal - LDL (low density lipoprotein) is bad cholesterol, helps cholesterol stick to artery walls (increases risk of heart disease)

Question 34

estrogen effect on CVD

Answer 34

- increases HDL - reduces LDL - increases vascular dilation - reduces coronary artery LDL uptake

Question 35

women risk of CVD compared to men

Answer 35

- reduced before menopause | - same after menopause

Question 36

HRT effect on CVD less than 10 years after menopause

Answer 36

decreases CVD

Question 37

HRT effect on CVD if given after 20 years after menopause

Answer 37

increased risk for CVD

Question 38

is HRT good for CVD

Answer 38

only in women under 60 years within 10 years of menopause

Question 39

HRT effect on colon cancer

Answer 39

reduces risk by 20% in post menopausal women

Question 40

HRT effect on brain

Answer 40

enhances mood and depressive symptoms

Question 41

HRT effect on DVT risk

Answer 41

increased but still low so only contraindicated if existing risk of DVT

Question 42

HRT effect on breast

Answer 42

higher risk of breast cancer but minimal if short term