DISCLAIMER Menopausetoday gives the following presentation for your

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 us@menopasuetoday. com 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, 2002 - Vol 288, No. 3 Women’s Health Initiative - Summary of results 3

WHI Study Design Two study arms: 1. Combined HRT vs Placebo Terminated Conjugated equine oestrogens (0. 625 mg) + medroxyprogesterone acetate (2. 5 mg) vs placebo 2. Oestrogen vs Placebo Ongoing Conjugated equine oestrogens (0. 625 mg) 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 -79 yrs (Average = 63 yrs) l l Recruited from 40 US centres between 19931998 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 Outcome (95% CI) Total Cardiovascular Disease Total Cancer 1. 17) Combined Fractures Total Mortality 1. 18) Global Index 1. 28) Women’s Health Initiative - Summary of results Hazard Ratio 1. 22 (1. 09 -1. 36) 1. 03 (0. 900. 76 (0. 69 -0. 85) 0. 98 (0. 821. 15 (1. 03 -

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 • Hip Fracture Women’s Health Initiative - Summary of results (from 16 to 10 cases) (from 15 to 10 cases)

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 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 1 tenth 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 wellbeing –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 Women’s Health Initiative - Summary of results