Ovarian failure/menopause Flashcards
Natural menopause definition
permanent loss of ovarian follicular activity
12 consecutive mo of amenorrhea
no other obvious pathologic/physiologic cause
avg age 51
Perimenopause definition
time prior to menopause and 1st year after menopause
Induced menopause definition
cessation of menstruation due to surgical removal of ovaries
OR iatrogenic ablation (chemo/radio)
Premature menopause/POI definition
menopause occurs >2 SD below mean age
FSH > 30 mIU/mL x 2 at least 1 mo apart
amenorrhea > 4 mo
preceded with a duration of disordered menses
Pathophysiology of menopause
depletion of ovarian follicles
reduced inhibin due to low FSH
increased activin - increases with reduced inhibin, tries to increase FSH
high FSH/LH
low Estrogen - dysfunctional granulosa cells
low progesterone
low androgen levels
Menopause symptoms
headaches/hot flashes teeth loosen, gums recede nipples become smaller and flatten breasts droop and flatten skin becomes drier, develops rougher texture backaches risk of CV disease abdomen loses muscle tone vaginal dryness, itching, shrinking stress/urge incontinence
Issues involved in ovarian failure
menstrual changes vasomotor symptoms urogenital changes mood changes sexual changes CVD bone health
Menopause - menstrual changes
Cycles initially get shorter before longer
- rapid follicular recruitment
- initially loop cycle: Luteal Out Of Phase follicular event (short)
- then lag cycles (long)
AUB
Depletion in primordial follicles
amenorrhea eventually occurs
LOOP cycle
Luteal Out Of Phase follicular event
premature formation of a follicle due to major surge in FSH during luteal phase
Lag cycles
Long follicular phase with aberrant folliculogenesis
high E2, low P4
Vasomotor symptoms during menopause
Hot flashes/night sweats
sudden onset - begins in chest, may progress to neck/face
often associated with anxiety, palpitations and sweating
can interfere significantly with life
75-80% of women experience them
generally from 6 mo - 5 y, but can last as long as 15 years
can occur in perimenopause
Etiology of vasomotor symptoms during menopause
Estrogen withdrawal --> Dysregulation of firing rate of thermosensitive neurons in preoptic hypothalamus decreased alpha2 activity significantly smaller thermoneutral zone
Management of vasomotor symptoms during menopause
Lifestyle - cool rooms, regular exercise, stop smoking
HT: estrogen alone or with progestin - lowest dose for shortest duration
Non-hormonal therapy: clonidine alpha 2 agonist
gabapentin
SSRI
Stellate ganglion block
Non-Rx - controversial, vitamin E??
Urogenical consequences of menopause
vaginal atrophy
UTI
incontinence
pelvic prolapse
Atrophy of urogenital epithelium and subepithelial tissues
Degeneration of collagen, elastin, sm
decreased blood flow to tissues
Estrogen-sensitive pelvic tissues
receptors found in: Introitus vagina bladder urethra pelvic floor musculature
Vaginal atrophy (menopause)
DYspareunia
vaginal dryness
itching
irritation
Pathophysiology of vaginal atrophy
thinning of epithelium less blood flow vaginal length/diameter shrink nerve endings exposed increased trauma
UTI during menopause pathophys
mucosa is thinner
glycogen production declines
decreasing level of lactobacilli
reduced lactic acid production
Urinary incontinence during menopause pathophys
reduction in mean uretrhal closure pressure
thinning of bladder mucosa and increased irritation
increased likelihood of urinary incontinence
Mood changes during menopause
some evidence for increased irritability, tearfulness, anxiety, poor concentration
secondary to - ??
- fluctuating E levels (E has positive effects on serotonin activity, upregulation of 5-HT1 receptors, decreased MOA activity)
- sleep disturbance
Depression during menopause
Risk factors:
- Hx of depressive disorders
- poor physical health
- Life stressors
- Hx of surgical menopause
- Long transition
Sexual concerns during menopause
Lack of E: dyspareunia, decreased vaginal blood flow, altered sesation
Reduction in ovarian testosterone
AUB is problematic
depressive symptoms
Managing sexual concerns during menopause
Address interpersonal/contextual components
Address biologic factors (AUB, vaginal atrophy, mood/anxiety)
Routine evaluation of hormone - limited value
testosterone therapy by experienced physicians
CVD during menopause
women who have had oophorectomy: higher age adjusted risk than those with intact ovaries
Adjusting for age, postmenopaulsa women - 2x risk seen in premenopausal
Less favourable lipid profiles
increased insulin resistance
increased likelihood of thrombosis
HT no longer indicated
Bones - menopause
Higher rates of fracture in postmenopausal women
loss of bone density
preservation of bone mineral density/fewer fractures with HT
Tx of osteoporosis in women
recommended for:
T-score =3% for risk of hip fracture
- FRAX >=20% for risk of a major osteoporotic fracture (forearm/hip/shoulder/clinical spine fracture) in next 10 years
Raloxifene, bisphosphonates, PTH, denosumab, calcitonin
POI - HT
premature menopause/ POI - associated with lower risk of breast ca and earlier onset of osteoporosis, CHD
HT recommended for them at least until median age of normal menopause
Considerations with HT use - cognition
WHI: no improvement in cognitive function
prospective study on women with mild-moderate AD: no effect for 1 yr on disease progression/cognitive function/global outcome
HT and breast cancer
HT use 1-4 y: no added risk
5 or more: RR 1.35, risk increased by 2.3% per year of use
elevated risk disappeared by 5 y after stopping
greater risk is still family history
HT and colon cancer
WHI observational
no protective effect on colorectal cancer mortality
HT and lung cancer
WHI: no significant increase in incidence
significant increase in death from lung ca in women who took EPT
HT and ovarian ca
current/recent use of MHT - RR 1.37 for serious endometriod ovarian cancer
HT and endometrial ca
only progestin / continuous combined reduces risk of endomterial ca
HT and stroke
EPT - no increase in stroke risk or an increased risk (HERS, WHI)
oral route higher RR than transdermal
HT and venous thromboembolism
no consistently observed procoagulant effect of HT in prospective studies
oral E mor econsistently affects coagulation and fibrinolysis and transdermal
HT and CHD
CV risks improve on HT in those >70 y (but not symptomatic for menopause)
HT conclusions
ET does NOT increase risk of CVD in early postmenopausal years, but increases it if begun some time after menopause
HT and gallbladder disease
increased risk
EPT risks
venous thromboembolism stroke (inconsistent data) breast ca for use beyond 5 y ovarian cancer gallbladder disease
EPT benefits
QOL
bone density
colon ca
ET in women with previous hysterectomy - risks
venous thromboembolism
storke (inconsistent)
ovarian ca
gallbladder disease
ET in women with previous hysterectomy - benefits
QOL
bone density
Causes of POI
Accelerated follicle depletion Primary hypogonadism Common causes: Turner Fragile X Somatic and X chromosome gene defects AI ovarian failure Toxins
Polyglandular autoimmune syndrome
adrenal, thyroid, pancreatic failure
Estrogen supplementation for depression
Not effective
