menopause Flashcards
(41 cards)
Menopause
Final menstrual period - defined once followed by 12 months of amenorrhoea.
Retrospective clinical diagnosis.
Given many women may not be naturally menstruation (contraception, hysterectomy/ablation) pragmatic definition is permanent cessation of ovarian function.
Early menoapuse <45years.
POI <40 years. (cessation of ovarian funciton before age of 40yrs)
Average age 51years in caucasians - varies across ethnicities.
AFC, AMH, early follicular FSH, inhibin B more useful in a fertility context and are not essential in diagnosis of menopause.
STRAW+10
Stages of Reproductive Aging Workshop.
Three broad stages.
Reproductive
Menopausal transition
Postmenopause
These three further categorised into -
early, peak (repro stage only) and late.
Can’t be used in POI, PCOS, those with hormonal suppresion of menstrual, endometrial ablation, removal of a single ovary or hysterectomy. In these woman supportive criteria should be used to determine reproductive stage.
POI
Primary hypogonadism prior to age 40 in women who previously had normal menstrual cycles.
Diagnosed:
- 2 x elevated FSH results (>40iu/l) 4-6 weeks apart.
- Characterised by menopausal symptoms and oligomenorrhoea or amenorrhoea.
1% <40
0.1% <30
POI risks
Premature morbidity and mortality
Impaired endothelial function, IHD, ischemic stroke, osteoporotic fractures, impaired cognition, diminished sexual well being.
POI etiology
Can be primary or secondary.
Primary:
Idiopathic (30% of these will have FHx suggestive genetic etiology)
Turner Syndrome (monosomy X, mosaicism, X chromosome rearrangements, X-autosome transloactaions, isochromosomes)
FMR1 premutation
Others genes (BMP15, INHA, GDF9, NOBOX, FSHRmutation)
Enzyme deficiencies
Autoimmune - polyendocrinopathy, polyglandular autoimmune diseases can occur. (AIRE)
Secondary:
Chemo
RT
Surgical - oophorectomy
Hyst/salpingectomy if blood supply to ovary comprimised
Infections
Inappropriate luteinisation of graafian follicles can occur (due to very high LH levels), prevents ovulation and pregnancy.
Investigations for POI
FSH, LH, E2, Testosterone, DHEAS, cortisol (morning), ACTH, TSH, T4, AMH
Karyotype and FMR1 gene mutation. (guidelines say in <30 yos)
Adrenal antibodies, thyroid antibodies, HbA1c.
Pelvic USS.
DEXA (dual xray absorptiometry) if concerns for BMD.
MHT for POI
Need higher doses than older women.
MHT may reduce symptoms and preserve bone density and should be advised until at least average age of menopause.
estradiol valerate - 2mg daily
CEE (conjugated equine estrogen) 1.25mg
Transdermal oestradiol 75-100mcg/24hour patch, twice weekly.
Ethinyoestradiol 10mcg daily
Or COCP (though may be suboptimal for bone and cardiovascular health, data lacking, small RCTs suggest MHT better for these)
Progesterone component.
Mirena - 20mcg/day - 52mg levonorgestrel.
Micronized progesterone - 200mg nocte 12 days per month or if continuous 100mg nocte.
Consideration of testosterone if hypoactive sexual desire dysfunction.
10mg/ml gel, apply 5 mg (0.5 mL) once daily to the upper thigh or buttock
Follow up of POI
Reviewed at least annually.
Assessment of symptom control. Adherence to tx. CVD assessment.
BMD ideally assessed every 2 years however availability of DEXA scans is limited.
Breast cancer screeninge every 2 years from 45-69 with a mammogram
Fertility options
- Oocyte freezing (if known risk whilst still fertile)
- Embryo freezing (as above)
- ovarian tissue cryopreservation and subsequent transposition (OTC) +/- IVF.
- Ovarian PRP (very experimental still)
- Donor oocyte.
- Donor embryo.
- Adoption.
- Childlessness.
Life style interventions for menopause.
Diet, nutrition
Exercise cardiovascular + weight bearing x2/week
Decrease caffeine
Decrease alcohol
Avoid smoking
Loose and cool clothing + layering
Environment
Weight management (obesity associated with more hot flushes)
Urogenital symptoms
female genital tract and lower urinary tracts both arise from urogenital sinus. Both are sensitive to effects of female sex steroid hormones throughout life. ER and PR found in vagina, urethra, bladder, pelvic floor.
Urinary incontinence - cochrane review (2012) showed systemic worsened incontinence.
Topical oestrogen - appears to be of benefit.
Recurrent UTIs
- Decrease vaginal pH and reverse the microbiological changes that occur in the vagina following the menopause (Cochrane review 2008)
SUI
Pelvic floor muscle training
Surgery
Overactive bladder
Lifestyle changes and bladder retraining
Antimuscarinics (oxybutynin)
Local e2 may have a role
Urogenital atrophy
Improves dryness, pruritis, dyspareunia
Cochrane 2016 low-quality evidence showing improvement in symptoms.
Osteoporosis - diagnosis/definition
Systemic skeletal disease characterised by diminished bone strength, with the risk of sustaining a fragility fracture (own body height fall)
Can occur from - failure to attain peak bone density, accelerated bone loss after menopause (induced by E2 deprivation), age related bone loss.
Definition - T-score <-2.5 (compared to healthy young persons bones) on DEXA or fragility fracture.
FRAX model used to determine risk of fracture over 10 years.
Appropriate assessment of fracture risk and secondary causes of osteoporosis should precede any therapeutic decisions
cardiovascular disease
Principal cause of morbidity and mortality in PM women.
Primary prevention measures.
Aspirin and statin use do not improve mortality in women (as they do in men).
- MHT likely cardioprotective if started around the time of menopause, and may be harmful if started more than 10 years after menopause.
- Cochrane showed reduction in all cause mortality in 50-59yos and cardiovascular mortality (Non SS)
Stroke
Risk may increase is MHT started >60
<60yo no increased risk (cochrane and WHI)
Risk related to oral therapy, no sig risk with transdermal.
VTE
Orally administered estrogen (estradiol or CEE) may exert a prothrombotic effect through the hepatic impact of these molecules. The prothrombotic effect is possibly related to high concentrations of estrogen in the liver due to the ’first-pass’ effect.
Most prevalent adverse effect of oral oestrogens.
Risk increases with age, weight and thrombophilias.
Epidemiological studies don’t show a link with transdermal E2 only oral.
Oral 6/10 000 women-years oral E+P (MPA and continuous higher risk
4/10 000 women-years oral E)
Neurological
MHT should not be used to enhance cognitive function.
MHT after onset of Alzeihmer’s does not benefit cognitive function or slow disease progression.
MHT initiation >60 increases risk of dementia
MHT initiation <60 decreases risk of dementia
Finding are inconsistent as to whether MHT improves depressive symptoms. Short term use for depression which commences during menopause transition may help.
Breast cancer
In low risk women the benefits of HRT for up to 5 years probably outweigh the harms.
Combined E+P increases risk of BC. Likely duration dependent.
- avoidance of synthetic progesterone may help
- it is not dose dependent.
E2 alone - no inc risk. Vaginal e2 - no inc risk.
Inc risk of BC with combined MHT assoc with addition of synthetic progestogen to oestrogen therapy (CEE + MPA continous combined therapy) and related to duration of use.
Risk may be lower with micronized progestogen or dydrogesterone.
Increased risk is small (extra 8 women per 10 000), risk decreases progressively after treatment stops.
Lack of safety data to support the use of MHT in breast cancer survivors.
Breast cancer risk should be evaluated before MHT prescription.
Estrogen alone decreases risk.
Endometrial cancer
Progesterone required to prevent EC due to unopposed oestrogen.
Blind endometrial sampling is appropriate for initial evaluation but is only reliable when endometrial cancer exceeds more than 50% of the endometrial surface area. [B]
Adequate doses of micronised P4 = 200mg per day for 10-14days or 100mg per day if continuous combined and E2 dose is <2mg or 50mcg.
Higher BMI patients may need higher Prog doses.
other cancers and MHT
colorectal - reduced
Ovarian - uncertain, likely not increased
Lung - E only, no risk. E+P non sign trend towards inc non small cell lung ca.
cervical - no increased risk
Upper GI - possible reduction in stomach, no effect on oesophageal
Androgens and menopause
Ovary - produces testosterone and androstenedione.
Adrenal cortex zona reticularis - produces androstenedione, DHEA and DHEAS.
Androgen precursors are converted to testosterone peripherally.
Androgen levels decline with age in women with no acute change associated with natural menopause.
Surgical menopause causes a significant drop in testosterone production.
Bioidenticals/Bioidentical hormone therapy (BHT)
Having the same molecular structure as a substance produced in the body. ie. oestradiol if manufactured is a bioidentical.
BHT poorly defined to describe compounded hormone preparations containing a mixture of various hormones, prepared by compounding pharmacies. Not subject to the same regulatory oversight. Can cause endometrial cancer if prog not sufficient for oestrogen dosing.
Menopausal symptoms
Indication for MHT:
VMS (Hot flushes/flashes), sweats/night sweats.
Urogenital symptoms
vaginal irritation, burning, dryness, dyspareunia, urinary frequency, urgency, recurrent UTIs
Sx that may be menopause associated:
Psychological (low mood, anxiety, irritability) - NOT depression
Disturbed sleep and frequent waking
Lessened sexual desire.
MSK pain (particularly Asian women)
74% of PM women <55years experience VMS.
28% have moderate to severely bothersome VMS.
33% ages 65-79 till have VMS.
Tesotserone therapy for postmenopausal
Transdermal therapy can be considered for hypoactive sexual desire dysfunction. Given in a female appropriate dose, may improve sexual desire, arousal, orgasm and pleasure.
Oral DHEA is not effective.
How does menopause cause bone loss
E2 promotes calcium absoprtion at the intestine
Increases renal conversion of calcium
Increases active form of Vit D and Vit D receptors on osteoblasts.
Promotes osteoblast formation through cytokines.
MHT and # prevention
MHT prevents bone loss and fractures in PM women (even those not at high risk of #)
Only therapy available with proven efficacy in those with osteopenia.
In those age 50-60 or within 10yrs of menopause - benefits of MHT (particularly transdermal + MP) likely outweight risk an can be considered first-line therapy.
Protective effect on BMD declines after cessation at an unpredictable rate.
Tibolone prevented vertebral and non-vertebral # in one RCT.
E2 and SERM - bazedoxifene together prevent bone loss, effect on # reduction not explored. (this combo also protect endometrium)
