Women’s Health Initiative - Summary of results DISCLAIMER Menopausetoday gives the following presentation for your information and to promote discussion. We welcome your comments We advise you if you have concerns to consult your doctor or local health department for further information.

Women’s Health Initiative - Summary of results Dr Beverley Lawton Dr Jill Shepherd 18/7/2002 comment on WHI study The following is a presentation covering the results of the recent WHI study. This is designed primarily for a medical audience Please feel free to send comments to and discussion will be reported under book exerpt

Women’s Health Initiative - Summary of results National Institutes of Health (NIH) Women’s Health Initiative (WHI) The Results JAMA, July 17, Vol 288, No.3

Women’s Health Initiative - Summary of results WHI Study Design Two study arms: 1. Combined HRT vs PlaceboTerminated Conjugated equine oestrogens (0.625mg) + medroxyprogesterone acetate (2.5mg) vs placebo 2. Oestrogen vs Placebo Ongoing Conjugated equine oestrogens (0.625mg) vs placebo

Women’s Health Initiative - Summary of results Combined HRT vs Placebo Study Design n=16,608 women with an intact uterus Age range= 50-79yrs (Average age = 63 yrs) l Recruited from 40 US centres between l Follow-up of 5.2 years (8.5 years planned)

Women’s Health Initiative - Summary of results Main Findings

Women’s Health Initiative - Summary of results Composite Outcomes for E+P OutcomeHazard Ratio (95% CI) Total Cardiovascular Disease1.22 ( ) Total Cancer1.03 ( ) Combined Fractures0.76 ( ) Total Mortality0.98 ( ) Global Index1.15 ( )  No difference in mortality and no overall increase in cancers

Women’s Health Initiative - Summary of results Main Findings: the Risks Per 10,000 women after 5 years there was an increased risk of: Breast Cancer (from 30 to 38 cases) Coronary Heart Disease (from 30 to 37 cases) Stroke (from 21 to 29 cases)

Women’s Health Initiative - Summary of results Main Findings: the Benefits Per 10,000 women after 5 years there were reductions in: Colorectal Cancer (from 16 to 10 cases) Hip Fracture (from 15 to 10 cases)

Women’s Health Initiative - Summary of results Absolute Excess Risks Absolute excess risks per 10,000 person years attributable to oestrogen+progestin were: 7 more CHD events 8 more strokes 8 more PEs 8 more invasive breast cancers The absolute excess risk of events included in the global index was 19 per 10,000 person years

Women’s Health Initiative - Summary of results Absolute Risk Reductions Absolute risk reductions per 10,000 person years attributable to oestrogen+progestin were: 6 fewer colorectal cancers 5 fewer hip factures

Women’s Health Initiative - Summary of results DSMB recommendation Study terminated because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect The global index statistic supported risks exceeding benefits

Women’s Health Initiative - Summary of results Study Conclusions Overall the health risks exceeded benefits from use of combined estrogen+progestin among healthy postmenopausal US women Results indicate that this regimen should not be initiated or continued for the primary prevention of CHD

Women’s Health Initiative - Summary of results Discussion points Significant study Breast cancer “strong trend” as rates not statistically significant Study stopped on breast Ca, and global trend not CHD events Trial could not distinguish the effects of oestrogen from progestin

Women’s Health Initiative - Summary of results Discussion points Older women – average age 63 years Not taking HRT for symptoms Large dropout rate – 42 % HRT group and 38% of placebo What is the significance of Progestin? Oestrogen arm had NO increased breast cancer rate and is continuing

Women’s Health Initiative - Summary of results The risk to an individual is small for example the increased risk for a women for 1 year for breast cancer is less than 1tenth of a per cent. Oestrogen alone appears to be safer as this arm is continuing.

Women’s Health Initiative - Summary of results Other issues not covered Quality of life Vaginal Health Cognition Gallbladder

Women’s Health Initiative - Summary of results Benefits of HRT

Women’s Health Initiative - Summary of results Established Benefits Eliminates hot flushes, night sweats, dry vagina, and palpitations. Reduces osteoporotic bone fracture (?P) Reduces colorectal cancer (?P)

Women’s Health Initiative - Summary of results Possible Benefits May increase mood and feeling of well- being –quality of life May reduce risk of Alzheimer’s disease May reduce arthritis May maintain dental health

Women’s Health Initiative - Summary of results Contraindications for HRT Active hepatitis- acute Previous DVT (?) MI in the last 6 months Undiagnosed vaginal bleeding

Women’s Health Initiative - Summary of results RISKS of HRT

Women’s Health Initiative - Summary of results Established Risks HRT increases the risk of VTE (?P) HRT increases the risk of non-fatal stroke (?P) HRT increases the rate of non-fatal MI (?P).

Women’s Health Initiative - Summary of results Established Risks 2 Estrogen increases the risk of endometrial cancer when it is taken without a progestin. HRT increases the incidence of gallbladder disease in some women

Women’s Health Initiative - Summary of results Possible Risks There may be an increased risk of breast cancer after taking HRT for five years or more (?P)

Women’s Health Initiative - Summary of results What to say to patients The risk to individual women is small and includes a small risk in DVT, stroke, CHD. No increased breast cancer risk in first 4 years of use (?P) Safe and effective for symptoms Effective for osteoporosis; but other medications longterm