Menopause Flashcards
what is the average age and range of menopause
~51yrs
45-55yrs
what is the menopause transition
when you start seeing changes i ncycle
what is perimenopause
menopausal transition + 1yr post menopause
what is considered early and premature menopause
early <45yrs
premature <40yrs
what happens biologically during the menopause transition
- FSH and LH
- E and P
- flow regularity and amount
- E types
↓ number and function of follicles + ↓ response to FSH and LH
No progesterone release = irregular + heavy (may also be lighter)
increased FSH and LH
prev more estradiol -. more estrone
increasing and fluctuating E and decreasing P in perimenopause
what happens to E and P in postmenopause
both plumet
what is estrone
⅓ potency of estradiol
Conversion in liver, androstenedione in peripheral tissue
what is estradiol
Most potent
Main endogenous hormone
Produced in ovaries
what is estriol
Least potent
Metabolite from estradiol and estrone
Highest levels in pregnancy as also produced by placenta
after menopause, where is estrogen made
androstenedione stored in body fat is converted into estrone which can be conv into estradiol
where is T made in women
25% ovaries, 25% adrenals, 50% peripheral conversion from androstenedione
T or F: T declines drastically after menopause
F- gradually as we age
unless surgical menopause- then decreases 50%
what is a dx of menopause
cessation of periods F12mths + elevated FSH (≥30mIU/ml)
is perimenopause dx with FSH levels
no
how long do VMS last
7-8yrs, median duration after last period ~4.5yrs
1/3 pts have it for 10yrs
what are VMS
hot flashes, night sweats
T or F: E levels predict severity of VMS
F
how does E changes in menopause cause hot flashes
↓E = ↓ endorphin conc in hypothalamus = ↑NE, ↓5HT levels = narrow thermoregulatory zone in hypothalamus (narrowed thermoneutral zone)
KNDy neurons in hypothalamus- control of thermoregulatory centers are stimulated by neurokinin B + inhibited by estrogen
↓ estrogen = hypertrophy of KNDy neurons = ↑activity = hot flashes
Target of new tx approaches for VMS (neurokinin 3 receptor antagonists)
when do VMS tend to peak
early in the evening
what is GSM
genitourinary sx of menopause
describe GSM sx and physiology
Degeneration of connective tissue (collagen, elastin, smooth muscle) = vaginal shortening + narrowing
Reduced vaginal blood flow and secretions
↓ Glycogen production = △ vaginal pH from acidic to alkaline (↑pH)
Thinning mucosa + ↓ blood flow = ↓ secretions
Sx: vaginal atrophy (dryness, irritation/ itch, dyspareunia, post coital spotting), lower urinary tract (recurrent UTI, LUTS), sexual fx (low libido)
what are some menopausal sx that are more common in perimenopause
breast tenderness, headaches
estrogens have a_______ effect on arteries
protective- prevents atherosclerosis
rapid effects of E on arteries
dilation and NO release
rapid effects of E on arteries
dilation and NO releasel
long term effects of E on CV health
↓atherosclerosis, vascular injury, smooth muscle cell growth ↑ endothelial cell growth
midlife changes on bone health
bone loss occurs at faster rate with loss of estrogens = always assess for osteoporosis RFs
midlife changes on cognition
estrogens modulate aspects of brain function (hippocampus) → NT (ie 5HT, NE, dopamine, ACh)
Loss of estrogens = may affect concentration, memory (esp verbal memory- what was that word?)
Eff on cognition LT unknown- is it the loss of estrogens or is it aging
early or premature menopause is associated with increased risk of
osteoporosis, CV disease, cog impairment/ memory, early mortality
lifestyle management of menopausal sx include
cooling techniques (layers, fan), avoid triggers (excessive alcohol, spicy foods), maintain healthy body weight, smoking cessation, exercise
what are phytoestrogens
plant compounds with estrogen like activity but 500-1000x weaker than estradiol
3 types of phytoestrogens
isoflavones
lignans
coumestans
3 isoflavones of soy
daidzein, genistein, glycetin
isoflavone supplement efficacy, how long to work, cautions
Marginal effect with hot flashes, inconsistent results
Takes 8-12wks to work
Food is a better source
Caution with hormone sensitive cancers and supplements
femarelle efficacy
RCT showed ↓in vasomotor sx, no adverse △ in breast or endometrium
black cohosh sus mech + AEs + efficacy
may act as a SERM, exact mech unknown
most studies have found no effect, but generally well tolerated
rare liver damage
what hormone replacement to use if pt has had a hysterectomy
E alone - no endometrial protection from systemic E required
systemic MHT is safe and effective for
healthy pts <60yrs of age or <10yrs after last menstrual period
For early or premature menopause, consider MHT until average age of menopause
why is P added in MHT
endometrial protection from systemic estrogen (prevents endometrial cancer)
what is E used for in MHT
sx management such as VMS + doses can be adjusted for sx management
vaginal estrogen is used for
1. GSM
2. VMS
1
what is the most common MHT regimen
EPT continuous
what is EPT cyclic
estrogen continuous, progestogen x12-14d
what is the timing hyp9othesis
: increased risk of atherosclerosis with age/ time after menopause (E is usually protective and prevents plaque formation)
If start E >10yrs after menopause = is actually harmful as it can dislodge the plaques that have already formed due to prothrombotic and proinflamamtory effects of estrogen
Primary benefit of MHT is <10yrs after menopause
what was the women’s health initiative
designed as an RCT to assess if MHT reduced CV morbidity and mortality (CEE and medroxyprogesterone were used)
describe the relationship between MHT and VTE
E has a dose dependent procoagulant effect
Increased risk of VTE with both WHI-EPT and ET with greatest risk in first year, with familial thrombophilia or other RFs
Transdermal E may have lower VTE risk, but are based on obs studies only (may just be d/t lower dose)
describe the relationship between MHT and CV risk
Age and time since menopause matter- those at high risk of CVD should avoid MHT (hx VTE, stroke, CHd event)
Mod risk with comorbidities may use transdermal or lower dose of E
Comorbidities: HPTN, smoking, obesity, DM
describe the relationship between MHT and breast cancer
EPT in WHI showed ↑ after 5yrs of use
ET alone did not show increase of breast cancer in WHI
May be differences in risk with type of progestogens - progesterone may have lower risk compared to synthetic progestins
Avoid MHT if personal hx of breast cancer
Caution if strong family hx
oral estrogen effects (TG, SHBG, TBG, CRP, hormones, lipids)
High first pass eff: ↑TG, SHBG, TBG, CRP
Some △ in hormones
Improve lipids ↑HDL, ↓LDL
when should you choose TD over PO estrogens
Avoid first pass effect: smokers, high TG, HPTN, ↓libido, gallbladder disease, RF for VTE/ CVD
For consistent lvls: migraine, shift workers, malabsorption issues
0.625mg CEE = ____ 17b-estradiol (oral) = __ug patch = ___pumps estrogel = ___ug EE
1mg
50ug patch
1-2 pumps
5ug EE
progesterone doses for systemic HT- continuous and micronized
P: continuous MPA 2.5mg or micronized progesterone 100mg daily// cyclic MPA 5mg or micronized progesterone 200mg F12-14d/mth
continuous EPT BTB is expected __________
up to 6-9mths after starting, if >!2 mths = investigate
cyclic EPT will lead to bleed when
withdrawal bleed when progesterone is stopped at the end of the 12-14d cycle
what is tibolone
Selective tissue estrogenic activity regulator (STEAR)- usually not 1st line
Synthetic steroid analogue of the progestin, norethynodrel
tibolone is converted into
3 active metabolites with estrogenic, progestogenic, and androgenic activity (doesn’t need + P)
androgenic eff of tibolone may help with
libido
AEs of tibolone
fatigue, breast tenderness, fluid retention, stomach upset/ nausea, increased appetite
Same risk profile as other MHTs
advantages of tibolone
less BTB compared to EPT, less mood effects b/c no progesterone
tissue selective estrogen complexes combined _____
E with a SERM
duavive is
bazedoxifen + CE
duavive effects
↓BTB and breast tenderness comp EPT
No increase in breast density (cancer)
bazedoxifen is a
SERM with antagonistic ER eff on uterus and breast- agonist eff on bones
Inhibits endometrial hypertrophy as an antagonist
bioidentical hormones are
chemically identical in molecular structure to human hormones
most MHT products come from
plant sources
biest =
estriol (80%) + estradiol (20%) or estriol (50%) + estradiol (50%)
triest =
estriol (80%), estradiol (10%), estrone (10%)
T or F:Natural progesterone creams (compounded) should not be used with estrogen for endometrial protection
T- lacks evidence that it will prevent endometrial hyperplasia
hormone customization for bioidentical hormones are made based on
blood levels or saliva testing
when to d/c MHT
Individualized decision on when to discontinue- decision to continue should be reassessed at regular intervals (ex- annually)
No age limit to continue MHT- can be continued as long as individual is getting benefit, even into 60s
Baseline risk changes over time
nonhormonal options for VMS
SNRIs/SSRIs
oxybutynin
gabapentinoids
clonidine
SSRI MOA in VMS
increase 5HT lvls in thermoreg zone
gabapentinoids MOA in VMS
for VMS unknown, may have direct eff on hypothalamic thermoreg center
clonidine MOA in VMS
centrally acting a2 adrenergic agonist, may decrease vascular reactivity
Not as effective as other nonhormonal rx options
nonpharm tx for GSM
regular sexual activity/ partner/ solo, dilators, pelvic floor physio, laser
nonhormonal GSM options
moisturizers and lubricants
what moisturizers can be used in GSM
polycarbophil
hyluronic acid
what hormonal therapies are available for GSM
vaginal E therapies
intarvaginal DHEA
ospemifene
systemic E therapies
ospemifene is an _______ for _____
oral SERM for vaginal dryness and dyspareunia
intravaginal DHEA AEs
vaginal discharge from melting of hard fat excipient in ovules
what is an Inactive sex steroid precursor converted to estroge and androgen in vaginal cell wall
intravaginal DHEA
waht are some vaginal estrogen therapies for GSM
estragyn
Estring
vagifem
