Menopause and HRT
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Transcript of Menopause and HRT
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Menopause and HRT
Maureen Mc Farland
October 2006
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Consultation
Ascertain menopausal status (LMP, symptoms, contraception)
Risk factors for CVD / VTE Risk factors for osteoporosis / breast Ca Woman’s personal views on the menopause
itself and on any interventions It is a woman’s evidence-based patient
choice to take or not to take HRT/ therapy Her decision recorded
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Menopause in perspective
Average age – 52 Average life expectancy – 81 and increasing women can expect to live around 30 years in
the postmenopausal state More women will live to be 100 Can now be considered to be a mid-life event
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Symptoms: vasomotor
About 70% in Western cultures will experience vasomotor symptoms
Prevalence highest in 1st year after FMP Sympathetic nervous control of blood flow to
the skin is impaired No reflex constriction to ice stimulus Serotonin and its receptors implicated
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Symptoms : psychological
While many symptoms have been associated with menopause
General population studies show most women do not experience major changes in mood
Likely to be associated with past problems and current life stresses
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Symptoms: sexual dysfunction
US National Health & Social Life Survey :
- SD is more prevalent for women (43%) than men (31%)
Population studies: numbers with FSD rise from 42% to 88% during early to late perimenopause (before FMP)
Underlying reasons for FSD are commonly multifactorial – hormonal and non-hormonal
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Long term complications of oestrogen deficiency
Greater bearing on women’s QOL Clinically silent for years Far greater problem in terms of morbidity,
mortality and economic burden
- Osteoporosis- CVD - Dementia- Urogenital atrophy
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Osteoporosis
1 in 3 women, 1 in 12 men National Institute of Health definition: -
skeletal disorder characterized by compromised bone strength predisposing to increased risk of fracture
Bone strength: integration of bone density and bone quality
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Determinants of bone mass:
Age – peaks mid 20s,
- begins to decline mid-40s
- accelerated rate of loss for 6-10 yrs after menopause
- slower rate of loss
- Seems sensible to encourage good diet in childhood, with exercise and no smoking – little evidence of efficacy of these
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Determinants of bone mass
Ethnicity and genetic factors – greater role than environmental influences
DMPA – relationship complex:- Amenorrhoea is associated with a 5-10% loss
of bone – not progressive- Patient’s own risk factors for OP- Should be stopped around 40- Long term effects on teenagers uncertain
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Risk factors for osteoporosis
Genetic – FH esp 1° relative with hip Constitutional – low BMI, early menopause Environmental – smoking, alcohol, diet,
sedentary Drugs – steroids Diseases – RA, neuromuscular,liver disease,
malabsorption, hyperparathyroid, hyperthyroid, hypogonadism
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Cardiovascular disease
Most common cause of death in women over 60yrs
Stroke – major cause of long term disability Oophorectomized women are at 2-3 fold
increase risk of CHD
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WHI (nearly 4 yrs ago)
Reported no beneficial effect and may increase the risk of CHD
BUT >20% of these women were >70yrs, mean age 63yrs
NOT age of typical menopausal woman with symptoms
WHI data overall cannot be used to discuss women <60yrs
WHI 50-59 – less CHD, CABG, PCTA, angina
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Danish Study
30% decrease in mortality from CHD
Interpretation: there may be a window of opportunity for CVD protection
No comment from regulating authorities
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Dementia
One of the major causes of disability world-wide
Women have a central role providing care and support to people with dementia
Swedish twin study 2005 (6604) Length of reproductive period and age at
menopause were inversely associated with risk of cognitive decline
Use of HT -> 40% decline in risk
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Urogenital Atrophy
Oestrogen deficiency after menopause cause atrophic changes in urogenital tract -> urinary symptoms eg frequency, nocturia, incontinence, recurrent infection.
These may co-exist with symptoms of genital atrophy – dyspareunia, itching, burning, dryness
Smoking decreases bioavailability of oestrogen -> inc symptoms
Timing of symptoms varies
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Vaginal atrophy
Pre-menopausal vaginal epithelium pH <4 Post-menopausal – glycogen depletion ->
loss of lactic acid-> vaginal more easily colonised by other bacteria
Changes in collagen in pelvic floor -> pelvic floor atrophy and shortened urethra
Women using systemic HT may need additional vaginal oestrogen
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Identify the “at risk” patients
Young women with premature menopause hormone profile in all hysterectomised
women women with fragility fractures Integrated care within a practice - include
Practice nurses doing “well-woman” clinics discharge letters from hospital
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examination
BMI BP Breast and pelvic examination ONLY if
clinically indicated (as with OCP) Encourage cervical and breast screening
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HRT Prescribing
Risk / benefit analysis
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Follow-up
3 months - symptom relief,
- persistence of s/es
- abnormal bleeding
- (BP) Yearly - risk / benefit discussion
- BP
- abnormal bleeding
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Investigations
FSH levels are only helpful if diagnosis is in doubt FSH not a guide to fertility status FSH no help in monitoring HRT Measure FSH if suspected premature Ov
failure Sample FSH ASAP after day 1 Oestradiol levels only useful for monitoring
non-oral HRT
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Investigations
TFT – abnormalities can be confused with menopausal symptoms
Urinary catecholamines – rare cause of hot flushes
Total testosterone unhelpful (Most bound to SHBG [2/3] or albumin [1/3] )
Free testosterone index not available routinely
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Investigations
Mammography: no evidence supports routine, over and above NHSBSP
Only 1 in 4 women on combined HRT showed increase breast density
Increase was 3%-6% MWS – observational data from uncontrolled
trials – increase interval cancers WHI O-only arm – NO increased Ca risk
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Side effects and Risks
Oestrogen-related: fluid retention, bloating, breast tenderness, nausea, headaches, leg cramps, dyspepsia
Progestogen-related: fluid retention, breast tenderness, headaches or migraine, mood swings, depression, acne, lower abdominal pain, backache
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Weight gain?
Major reason given why women are reluctant to try HRT
BUT Randomized placebo-controlled trials
repeatedly show no evidence of HRT – induced weight gain!
Oestrogen deficiency alters fat metabolism -> increased male distribution of fat deposition
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Abnormal vaginal bleeding
With sequential – change in pattern or BTB CCT – persists > 4-6 months Concordance, other medication Examine, cervical cytology / Chlamydia TVS – endometrium > 4 mm – endometrial
biopsy / hysteroscopy
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HRT and risk of VTE
HRT is associated with significant (but small ) increased risk of thrombosis & stroke
Possibly worse in first years of treatment No increase with transdermal oestrogen If high risk for VTE – consider transdermal
eg women with BMI >30,
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WHI data (average age 63yrs)
Extra 7 CHD events per 10,000 Extra 8 strokes per 10,000 Extra 8 breast cancers per 10,000 Extra 18 VTE per 10,000 5 less hip fractures per 10,000 6 less colorectal Ca per 10,000 total mortality - no significant difference
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Breast Cancer data
Breast cancers from age 50 - 70 /1000 women
time on HRT Breast Cancers extra Ca
never 45 per 1000 -
5 years use 47 per 1000 2 / 1000
10 yrs. use 51 per 1000 6 / 1000
15 yrs. use 57 per 1000 12 / 1000Beral et al Lancet 1997
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WHI breast Ca risk data for 5 years use per 1000 women
Increase only seen in combined therapy
Age absolute difference in risk (death)
50-59 +3 (+1.4)
60-69 +4 (+1.5)
70-79 +7 (+2.2)
All +4 (+1.8)
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Osteoporosis Clear evidence of reduced hip and spinal
fracture risk with lower doses Long-term treatment needed for ongoing
fracture prevention Regulatory authorities Dec 2003: HRT not
to be used as a first line prevention Alternatives are available for prevention
and treatment in older women Oestrogen - best option in women who are
younger or symptomatic or both
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Osteoporosis
NICE guidelines next year Calculation of 10 year fracture risk Cost of achieving gain in QALY Focus is moving away from prevention, and
towards older age groups (GP contract has failed to reward OP
management)
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Osteoporosis
Anti-resorptive agents – oestrogen, SERMs, Bisphosphonates, calcitrol, calcitonin
Anabolic agents – Teriparatide ( pulsed subcutaneous administration parathyroid hormone)
Dual action – strontium (Protelos) Women >65 who show unsatisfactory response to
bisphosphonates – PTH (osteonecrosis of jaw – seen in high dose
bisphosphonates used to treat Ca)
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Summary
Decision making is based on Negotiation indication should dictate the duration HRT remains treatment of choice for relief
of symptoms and early prevention of Osteoporosis
Switch to period - free once clearly postmenopausal
Lower dose preparations are better tolerated
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Summary
indications for longterm (> 10 yrs.)HRT:
-continuing symptoms
- benefits outweigh risks
-no alternative for osteoporosis reassess individual risks regularly in light of
changing personal circumstances and new data
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Women in the Autumn of their lives deserve an Indian Summer, rather than a Winter of Discontent
Robert Greenblatt