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Managing the Menopause

Managing the Menopause. Dr Julie Ayres Specialty Doctor in Gynaecology LTHT BMS Council. Management of the menopause with hormones. The menopause Definition Symptoms HRT Where are we now with it? Risks and benefits Who for? Which type?. The Menopause -Definition.

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Managing the Menopause

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  1. Managing the Menopause Dr Julie Ayres Specialty Doctor in Gynaecology LTHT BMS Council

  2. Management of the menopause with hormones • The menopause • Definition • Symptoms • HRT • Where are we now with it? • Risks and benefits • Who for? • Which type?

  3. The Menopause-Definition • The last menstrual period • i.e. only diagnosed in retrospect 12 months later

  4. When should we expect symptoms?

  5. Symptoms of the menopause?

  6. Menopausal symptomsVasomotor

  7. Menopausal SymptomsGenitourinary

  8. Menopausal Symptoms – Weight gain

  9. Menopausal Symptoms - confusion

  10. Menopausal symptoms – poor concentration

  11. Menopausal Symptoms – feeling more emotional

  12. Osteoporosis • Fractures • Wrist • Hip • Spine • Height loss • Dowager’s Hump • Back Pain

  13. Predictions about the menopause • It will happen • It will be unpredictable

  14. Menopausal women need help and advice

  15. Hormone Replacement Therapy - WHY? • Problem? • Oestrogen deficiency • Answer? • Oestrogen replacement

  16. HRT – Ups and Downs • HRT History • Used x 60 years+ • Past Issues • Endometrial cancer • Add progestogen (combined HRT) • Reduced risk of CHD • Reduced risk of osteoporosis • It was looking good! • Breast cancer • WHO data • RR 1.35

  17. HRT – More Ups and Downs Increased risk of Heart disease/Stroke • WHI (2002) • Many women stopped HRT altogether • Many doctors advised against starting/continuing HRT Higher risk of breast cancer • MWS (2003) • Many more women just stopped HRT • CSM reviewed WHI / MWS and issued guidance • Dec 2003 • ‘Knee-jerk reaction’ • ‘HRT TO BE USED AT THE LOWEST DOSE FOR THE SHORTEST POSSIBLE TIME’ • ‘Final nail in the coffin’ for prescribers

  18. HRT - Benefits • Well-established • CONTROL OF MENOPAUSAL SYMPTOMS • Maintenance of bone density • Reduction in risk of OP fractures • CSM advise not for first line use

  19. HRT - Benefits • Other benefits? • Reduced risk colon cancer • Observational studies • Alzheimer’s disease? • Jury is out • Coronary Heart disease • - benefit or risk?

  20. HRT – Risks • DVT • Stroke • Breast Cancer • Coronary Heart disease • Risk or benefit?

  21. HRT – Possible CV benefits? • Nurses Health Study • Observational study of 120 000 US nurses • 50% reduction in incidence and mortality from coronary heart disease • No effect on risk of stroke • NEJM M. Stampfer et al. 1991; 325 (11):756-762 • Other observational studies suggested similar benefits

  22. HERS Study • Secondary prevention study in 2763 women with CHD • RCT using CEE/MPA vs. placebo • 50% inc in ischaemic events in 1st yr in HRT group • No overall benefit at 5 and 7 years • JAMA 1998; 280: 605-13

  23. HRT Headlines

  24. WOMENS HEALTH INITIATIVE • RCT • Designed to • last for 8.5 years • look at major health benefits and risks associated with the most commonly used HRT in the US i.e. CEE +/- MPA against placebo • JAMA 2002; 288: 321-33

  25. WHI Aims • Primary outcome measure = CHD • (non-fatal MI + CHD death) • Primary adverse outcome = invasive breast cancer • Global index summary included; • Hip fracture and colorectal cancers • Stroke,PE,endometrial cancer and deaths due to other causes

  26. WHI Cont • Combined arm (CEE + MPA) • 16,608 postmenopausal women aged 50 to 79 years • terminated early (5.2 years) • Numbers of CA Breast exceeding stopping boundary • Oestrogen only arm continued

  27. WHI Results • Estimated hazard ratios; • CHD 1.29 • Ca Breast 1.26 • Stroke 1.41 • PE 2.13 • Colorectal Ca 0.63 • Endometrial Ca 0.83 • Hip fracture 0.66 • i.e. Relative risks

  28. WHI Results • Absolute risks - I.e. XS cases per 10,000 women years • CHD 7 extra cases • stroke 8 • PE 8 • invasive breast cancer 8 i.e. 38 vs. 30 • THESE REPRESENT VERY SMALL RISKS TO THE INDIVIDUAL

  29. WHI Results • Absolute risk reductions (per 10,000 women years) • colorectal cancers 6 • hip fractures 5

  30. WHI - WHAT THE PAPERS DIDN’T SAY • The oestrogen-only arm continued, • XS CVD risk appeared to be assoc with combined HRT • Only CEE and MPA were studied • Study Population • Average age of women was 63 • Ave time since menopause = 12 years • CV risk profile • BP 36.1% • High BMI 28.5% • Diabetes 4.4% • High chol. 12.7% • Previous history of CHD not excluded (except during the previous 6 months) • 7% had history of CHD • All women asymptomatic

  31. Summary of Unreported Data • Entry criteria do not reflect standard practice in the clinical selection of women for HRT

  32. WHI - What have we learnt? • Breast Cancer? • Confirms increased risk Ca Br with longer term use of combined HRT (CEE and MPA) • Use > 10 years • i.e. > 5 years use during study - only in women who had used HRT for 5 years previously

  33. WHI – What else have we learnt? • Confirms reduced risk of OP fractures • Confirms reduced risk of colorectal cancer • (combined HRT)

  34. WHI - What else have we learnt? • Cardiovascular disease? • Suggests possible increased risk of CVD assoc with CEE and MPA • IN THIS POPULATION • These data should not be applied to other types, doses and routes of HRT • ? effect of different hormones • (WHISP trial-1mg E2/0.5mg NET) • ?Primary prevention (as in observational studies) only applies to women without pre-existing atherosclerosis • 50-59 years (WHI) – appeared at reduced risk

  35. WHI - Overall Conclusion • Don’t give HRT to women who don’t need it! • We still didn’t know about the effect of HRT on the CVS in younger women.

  36. HRT and Breast Cancer – The Bad News • Daily Mail – Aug 2003 • “HRT doubles the risk of breast cancer!”

  37. MILLION WOMEN STUDY • Accepted that; • - HRT increases risk of breast cancer • Designed to; • - Assess effects of specific types of HRT on incident and fatal breast cancer

  38. Million Women StudyRecruitment • 1 084 110 women aged 50-64 years attending NHSBSP = quarter of British women between 50-64 • Observational study • Questionnaire completed before screening • Average follow-up: 2.6 years (incidence) 4.1 years (mortality)

  39. Million Women Study - Results • RR Ca Br ever users = 1.43 cf never users • In current users only • RR 1.66 • RR 1.01 in past users • slightly increased in 1st year after HRT use • no different to never users thereafter

  40. Million Women Study - Results • RR in users of E only (Ca Br) = 1.30 • RR in users of E+P = 2.00 • RR in users of tibolone = 1.45 • Risk increased for increasing duration of use • RR death from Ca Br • Current users = 1.22 • Past users = 1.05 • Not statistically significant

  41. Million Women Study - Results • No significant variation between different oestrogen types, doses or routes (oral / transdermal / implants) • No significant difference between different progestogen types (MPA / norethisterone / norgestrel) or sequential / continuous • Only factor modifying risk was low BMI • BMI <25 - RR 1.97 • BMI >25 - RR 1.46

  42. Million Women Study - Results • In developed countries the risk of breast cancer in never users = est @ 20/1000 between 50 and 60 • Collaborative group figures • Using the RR estimates from this study the different patterns of use of HRT would be expected to result in……...

  43. Estimated Extra Cases of Breast Cancer per 1000 Women by 60y • 5 years E from 50y - 1.5 extra cases • 10 years E - 5 extra cases • 5 years E+P - 6 extra cases • 10 years E+P - 19 extra cases

  44. Million Women Study - Potential Biases • Observational study • ?Differences between women attending NHSBSP or not (75% attend) • ?Effect of women not participating (71% participated) • ?Results overestimated because of increased durations of treatment (from baseline to diagnosis)

  45. Million Women Study in Context • Study confirms increased risk of breast cancer associated with HRT • Study suggests 20 000 extra breast cancers in UK due to HRT in past 10 years • 15 000 due to E+P • 5 000 due to E • Postmenopausal obesity - 50 000 • Alcohol intake 45-64y - 16 000

  46. What does the evidence suggest about HRT and breast cancer? • Putting all the evidence together (45 studies) • Risk estimates vary++ with a number of studies showing no increase in risk • 20% - RR < 0.9 • 33% - RR >1.1 • 47% - RR 0.9 – 1.1 • MWS is a clear outlier, with much higher risk estimates than all other studies • Bush et al Obstet Gynecol 2002;98:498-508

  47. HRT and Breast Cancer – The Good News • WHI – Oestrogen only arm • 11000 women on CEE • Terminated at 7 years • No benefit on CHD risk • Slightly increased risk of stroke (12/10000) • Reduced risk hip fracture • No effect on colon cancer • NO INCREASE IN BREAST CANCER • RR 0.77 (not statistically significant)

  48. WHI revisited • Average age = 63 • Ave 12 years since menopause • 70% women over 60 • To achieve sufficient power in the study • Assumption made re protective effects being same at all ages • Study not powered to do subgroup analysis by age

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