Menopause and HRT

1. Menopause and HRT Maureen Mc Farland October 2006

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. Danish Study • 30% decrease in mortality from CHD • Interpretation: there may be a window of opportunity for CVD protection • No comment from regulating authorities

15. 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

16. 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

17. 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

18. 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

19. examination • BMI • BP • Breast and pelvic examination ONLY if clinically indicated (as with OCP) • Encourage cervical and breast screening

20. HRT Prescribing • Risk / benefit analysis

21. Follow-up • 3 months - symptom relief, - persistence of s/es - abnormal bleeding - (BP) • Yearly - risk / benefit discussion - BP - abnormal bleeding

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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,

29. 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

30. 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 / 1000 Beral et al Lancet 1997

31. 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)

32. 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

33. 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)

34. 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)

35. 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

36. 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

37. Women in the Autumn of their lives deserve an Indian Summer, rather than a Winter of Discontent Robert Greenblatt