1. WHI Overview of Principal Results Vanessa M. Barnabei, MD, PhD Medical College of Wisconsin Obstetrics and Gynecology

2. Cardiovascular Disease E+P8506PL8102HRE5310PL5429HR CHD(total)1881471.241771990.91 CHD Death 39341.1054590.94 Stroke(total)127851.411581181.39 Fatal16131.2015141.13 Non- fatal 94591.50114851.39

3. Venous Thromboembolism E+P8506PL8102HRE5310PL5429HR VTE(total)151672.11101781.33 DVT118522.0777541.47 PE70312.1348371.34

4. Breast Cancer E+P8506PL8102HRE5310PL5429HR Total2451851.24 In situ 47371.18 Invasive1661241.26941240.77

5. Fracture E+P8506PL8102HRE5310PL5429HR Hip Fx 44620.6638640.61 Vertebral Fx 41600.6639640.62 Total6507880.765037240.70

6. Quality of Life

7. Symptom Relief: Effects of E+P In women symptomatic at baseline: In women symptomatic at baseline: – Improvement in: Hot flashes Hot flashes Night sweats Night sweats Vaginal dryness Vaginal dryness Joint pain/stiffness Joint pain/stiffness General aches and pains General aches and pains Younger, thinner women got the most relief from vasomotor symptoms Younger, thinner women got the most relief from vasomotor symptoms

8. Side Effects of E+P In women asymptomatic at baseline: In women asymptomatic at baseline: – Worsening of: Breast tenderness Breast tenderness Vaginal discharge Vaginal discharge Vaginal irritation Vaginal irritation Headache Headache Older, thinner women more likely to develop breast tenderness Older, thinner women more likely to develop breast tenderness

9. Protective Effects of E+P In women asymptomatic at baseline: In women asymptomatic at baseline: – Protection from: Hot flashes/night sweats Hot flashes/night sweats Vaginal dryness Vaginal dryness Joint pain/stiffness Joint pain/stiffness General aches and pains General aches and pains Lower back pain Lower back pain Neck pain Neck pain Protective effect on joint symptoms seen in all age groups Protective effect on joint symptoms seen in all age groups

10. Bleeding: Effects of E+P E+P: E+P: – At 6 weeks: 42.5% – At 6 months: 54.0% – At 5 years: 13.1% Women who were older, further from LMP, thinner and never/past HRT users were more likely to report bleeding Women who were older, further from LMP, thinner and never/past HRT users were more likely to report bleeding

11. Summary: Symptoms (E+P) Vasomotor symptoms common in younger postmenopausal women Vasomotor symptoms common in younger postmenopausal women Musculoskeletal symptoms very common in all age groups Musculoskeletal symptoms very common in all age groups E+P relieved and prevented vasomotor and musculoskeletal symptoms E+P relieved and prevented vasomotor and musculoskeletal symptoms Women most likely to benefit from E+P are younger, symptomatic women Women most likely to benefit from E+P are younger, symptomatic women

12. WHI E+P and E-Alone Trials: Absolute (annualized) Risk Risks Benefi ts RiskBenefit Risk?Benefit?

13. WHI Publications Almost 400 manuscripts published or in various stages of preparation through Publications committee Almost 400 manuscripts published or in various stages of preparation through Publications committee Over 200 ancillary studies approved, most with outside funding Over 200 ancillary studies approved, most with outside funding Large database available with demographic, reproductive, health information Large database available with demographic, reproductive, health information

14. Biomarkers Many ancillary studies utilize blood, serum, and DNA available through WHI Many ancillary studies utilize blood, serum, and DNA available through WHI Available analytes include: Available analytes include: – Hormones and receptors – Growth factors and receptors – Lipids – Vitamins, etc. – DNA such as CYP, MTHFR, TNF

15. Ancillary Studies-Examples “Hormones and biomarkers predicting stroke in women” (OS) “Hormones and biomarkers predicting stroke in women” (OS) “Biochemical and genetic determinants of fracture in postmenopausal women” (OS) “Biochemical and genetic determinants of fracture in postmenopausal women” (OS) “Decision-making about cancer screening among older women” (HT-CT) “Decision-making about cancer screening among older women” (HT-CT) “Prevalence and natural history of autoimmune thyroid disease in postmenopausal women” (OS) “Prevalence and natural history of autoimmune thyroid disease in postmenopausal women” (OS)

16. Ancillary Studies Complete list of studies, biomarkers available from WHI investigators Complete list of studies, biomarkers available from WHI investigators WHI investigator must be a co-investigator WHI investigator must be a co-investigator All proposals for ancillary studies must be approved by Publications and Proposals Committee of WHI All proposals for ancillary studies must be approved by Publications and Proposals Committee of WHI