wk 12, lec 2 Flashcards
two types of menopause
physiologic and artificial
physiologic menopause
natural process via depletion of ovarian follicles
oocyte depletion (gradually lost over years via ovulation and atresia)
2 key processes in menopuase
loss of gonadotropin responsive oocytes
remaining oocytes become unresponsive to gonadotropins
gonadotropin levels (FSH, LH) in menopause
high (bc of ovarian failure)
what factor accelerate menopause
smoking
(not age, childbearing, weight, OCP)
premature menopause (primary ovarian insufficiency)
cessation of menstruation before age 40
-genees, autoimmune, radiation, chemo, tumor, infection
artificial menopuase
cessation of ovarian function bc of medical intervention
chemo, radiation, oophorectomy (remove ovaries)
indications for artificial menopause
-endometriosis
-estrogen sensitive cancers
-intra-ab disease (i.e fibroids)
-prophylactic oophorectomy (BRCA gene)
androstenedione and testosterone and DHEAS changes in menopause
A: drops a lot
T: stable
DHEA: decrease a lot (adrenopause)
estrogen changes in menopause
estradiol drops a lot (comes from estrone conversion and ovarian secretion)
estrone more stable bc of peripheral conversion (from aromatization of androstenedione in fat, muscle, liver)
progesterone changes in menopuase
source: corpus luteum in premenopausal, and adrenal secrete post menopause
drops lots
gonadotropins (LH and FSH) post menopuase
increase lots becasue lack of ovarian feedback from estradiol
pulsatile release remains but with greater amplitutde
FSH levels rise earlier and are higher than LH
2 criteria for diagnosis of menopause
FSH > 40 IU/L and estradiol < 75 pmol/L.
- No need to measure LH clinically for menopause confirmation.
androgen, estrogen, progesterone, gonadotropin changes in menopause
- Androgens: Decrease in androstenedione, mild decrease in
testosterone. - Estrogens: Major drop in estradiol, moderate decrease in estrone.
- Progesterone: Significant decline; adrenal source only.
- Gonadotropins: Large increase in LH & FSH due to loss of ovarian
feedback.
clinical implications of homrone changes in menopause
decrease estrogne= osteoporosis, CVD, vasomotor sx
persistent androgens: hirsutism, defeminization
high LH and FSH: ovarian failure and also stimulate androgen secretion
perimenopuase
over aging the mean cycle length shortens
** Shortening of follicular phase; luteal phase remains constant
hormonal changes after age 45 in perimenopause
shorten follicular phase
lower estradiol
elevated FSH
LH unchanged
perimenopause; role of inhibin in FSH regulation
inhibin via granulosa cells; negative feedback on FSH
ovarian reserve declines –> inhibin level drop
leads to increased FSH
transition to menopause changes
- Marked by menstrual irregularity
- Variability in cycle length increases
- Shorter transition in women with early menopause
- Longer transition in women with later menopause
perimenopause and estrogen and impacts
not a state of estrogen deficiency!
can have higher estradiol levels (irregular secretion)
Occasional corpus luteum formation with limited progesterone
secretion
Increased risk of endometrial hyperplasia due to unopposed estrogen
sx: irregular bleed, hot flash, mood swing
hromones in perimenopause
Elevated FSH and irregular estradiol secretion
pros and cons of uterine atrophy in menopause
shrink endometrium and myometrium
pro: reduce fibroids, adenomyosos, endometriosis
risk: Postmenopausal bleeding from atrophic or hyperplastic
endometrium.
ovarian and oviduct changes in menopuase
decrease in size
palpable ovaries in post menopause –> possible ovarian neoplasm
reproductive tract changes in menopusae
pelvic floor weak; prolapse
vaginal atrophy; flatten rugae and thin epithelium
vaginal pH increase- predispose to infections (staph, strep, dip.)
cervical atrophy- vaginal dryness and dyspareunia
libido in menopause
- Decline in estrogen → vaginal dryness, discomfort with sex
- Decrease in testosterone → reduced sexual desire
- Changes in progesterone → mood changes that may indirectly affect
libido
psychological and social: sleep, mood, stress, self image, relationships
urinary tract changes in menopause
- Atrophic Cystitis: Urgency, frequency, incontinence, dysuria.
- Recurrent UTIs: Due to thinning of bladder & urethral epithelium.
- Urethral Caruncle: Pouting meatus, possible dysuria & hematuria.
mammary gland changes in menopause
breast regression
resolve breast pain and cysts and cyclic sx
CVD system and estrogen and menopause
estrogen decerases CVD risk (decrease in menopause)
benefits:
* Improves lipoprotein profile
* Promotes vasodilation
* Inhibits vascular injury response
* Reduces atherosclerosis
risks:
* Promotes coagulation
* Increases thromboembolic events
bone metabolism and impacts of menopause of which type of bone
cortical bone: dense, in appendicular skeleton (i.e. legs, arms)
trabecular bone: porous, metabolically active, in axial skleleton (i.e. spine, pelvis, femur)
–> respond to hormones; loss of estrogen
RANK/RANKL/OPG pathway
osteoblasts express RANKL (ligand)
RANKL bind RANk receptors on osteoclast precursors –> promote osteoclast formation and activity
osteoprotegerin (OPG), secreted by osteoblasts, inhibits RANKL by binding it
= regulate bone turnover
impacts of estrogen on bone remodelling and the RANK/OPG system
- Suppresses RANKL expression
- Stimulates OPG production
- Inhibits osteoclast formation and activity
–> so in postmenopause: a decrease in estrogen causes more RANKL and less OPG
–> excess osteoclast; and bone resorption and bone loss; postmenopausal osteoporosis
RANK + RANKL= osteoclast make
OPG + RANKL = inhibit osteoclast
mood changes in menopause from hormones
- Estrogen fluctuations affect serotonin and other mood-related
neurotransmitters. - Progesterone changes may influence GABA pathways (calming
effect). - Lower hormone levels may heighten emotional sensitivity.
sleep in menopuase
bad especially in late menopausal transition
night wakings and hot flashes
sleep disordered breathing
homrone therapy may help with sleep and hot flashes
condition in menopause
memory decline is age related; some show more so in menopuase
estrogen neuroprotective
high progesterone for mood and cognition
risks: alcohol, smoke, TIA, hypertension
vasomotor sx in menopause
hot flash usually 4.5 yrs
begin with pressure in head –> increase to physiologyc flush
palpitation, hot face neck and chest, sweat
moments to 10 mins
experience of hot flush
- cutaneous vasodilation and increased perspiration
- ↓ Core body temperature
- ↑ Pulse rate
- No significant changes in heart rhythm or BP
thermoregulatory dysfunction in menopuase causing hot flashes
defect in central thermoregulation
set point narrows; so minor temp changes trigger heat-loss mechanisms –> sweat, vasodilate
thermoregulatory center: rostral hypothalamus
estrogen withdrawal hypothesis of hot flashes in menopause
not triggered by low estrogen alone (ie.. prepubertal kids dont have)
occur after estrogen exposure is withdrawn (i.e. menopause, oophorectomy)
neurochemical factors in hot flashes
NE increases post-flush (narrows thermo-neutral zone)
serotonin; thermostimulus increase serotonin receptor –> hot flush
SSRIs can improve VMS
associated with LH surges but not caused by
- Kallmann’s syndrome (no GnRH) → still experience flushes
- Hypothalamic amenorrhea (low estrogen, no flushing) suggests:
- Dopamine & opioid suppression of GnRH → protective?
