Sept10 A1-Hormone Replacement Therapy Flashcards
HRT def
using E and P
normal E drop in men and women in life
- 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)
normal testo drop in men and women in life
-men drops slowly in life and always have much more than
women
-women same slow drop but always much less
menopause def
permanent cessation of menstruation resulting from loss of ovarian fct
FSH and LH after menopause
high levels bc no P and E
why less P and E after menopause
- no more coming from follicles (theca cells and GCs)
- comes fro mother sources
source of estradiol and estrone after menopause
estradiol from adrenals
estrone from adipose tissue
receptors for estrogen
- nuclear Rs ERalpha and ERbeta. turn on gene expression. diff effect in diff tissues
- GPCRs for E
location of estrogen R in the body + most important ones that HRT works on
- brain
- heart
- liver (so E can regulate prot synthesis)
- breast
- uterus
- bone
- HRT especially for osteoporosis and heart disease*
ERalpha and beta diff and significance
- 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
Rs for progesterone
- PRa and PRb (nuclear)
- GPCR
ERa and ERb vs PRa and PRb
- ERa and ERb = 2 diff genes
- PRa and PRb = 1 gene undergoes alternative splicing
Rs for progesterone are where
- CNS
- hypoth
- systemic (metabolism)
- endometrium
- mammary glands
name of HRT with estrogen only
not called HRT but called ERT (estrogen replacement therapy)
why add P with E to make HRT
give HRT to women with a uterus to avoid increased risk of endometrial cancer than comes from ERT
early sx in menopause
don’t last long, short-lived. weeks to months
- hot flashes
- insomnia
- moodiness
intermediate sx in menopause
months to years
- vaginal atresia
- bladder dysfunction
- skin atrophy
late sx in menopause
years to decades
- osteoporosis
- CVD
does HRT work for hot flashes (early sx)
yes
does HRT work for vaginal dryness (interm sx)
yes but give as local low dose vaginal cream
do phytoestrogens from some vegan food work as an alternative to HRT
maybe, limited evidence. not being tested well
osteoporosis (late sx) def
decrease of bone mass density with aging
-is much greater in women due to menopause
RFs for osteoporosis
- 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
bone homeostasis
- osteoblasts making bone
- osteoclasts break down bone and remodel it
- E inhibits osteoclastic activity
- at menopause, osteoclastic activity increases bc of E drop
what happens when lost bone density and then start taking HRT
you stop losing bone density and your current bone density is maintained
alternatives to HRT for osteoporosis
- 1500 mg Ca per day
- 800 IU vitD per day
- biphosphonates and other meds
- act on the risk factors
- proven to decrease fractures probability*
mech of action of biphosphonates
- incorporate in PO4 and OH of bone matrix
- osteoclast eat the BPP while remodelling the matrix
- BPP kills the osteoclast that ate it
risk of BPP
rare type of femur fracture
osteoporosis, if pharmacology therapy is indicated, what are the meds that can be used
- BPP
- selective estrogen R modulator
- PTH
- estrogens
- calcitonin
SERMs mech of action
- 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)
perfect SERM would do what
- strengthen bone
- lower LDL cholesterol and raise HDL cholesterol
- relieve hot flashes
- reduce breast cancer risk
- reduce uterine cancer risk
one example of SERM
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)
HDL vs LDL
- 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)
estrogen effect on CVD
- increases HDL
- reduces LDL
- increases vascular dilation
- reduces coronary artery LDL uptake
women risk of CVD compared to men
- reduced before menopause
- same after menopause
HRT effect on CVD less than 10 years after menopause
decreases CVD
HRT effect on CVD if given after 20 years after menopause
increased risk for CVD
is HRT good for CVD
only in women under 60 years within 10 years of menopause
HRT effect on colon cancer
reduces risk by 20% in post menopausal women
HRT effect on brain
enhances mood and depressive symptoms
HRT effect on DVT risk
increased but still low so only contraindicated if existing risk of DVT
HRT effect on breast
higher risk of breast cancer but minimal if short term
