Cardiovascular Disease in Women Module VI: Update on Menopausal Hormone Therapy and Selective Estrogen Receptor Modulat

1. Cardiovascular Disease in WomenModule VI: Update on Menopausal Hormone Therapy and Selective Estrogen Receptor Modulators (SERMs)

2. Menopausal Hormone Therapy • Observational Data and Assumptions • Randomized Trial Data • Summary of Current Prescribing Guidelines

3. “Hormone Replacement Therapy” Risk-Benefit Balance: 1960’s-1990’s Benefits CHD Osteoporosis Vasomotor Symptoms GU Symptoms Skin Preservation Risks Source: Limacher 2002

4. Postmenopausal Estrogen Therapy • Meta-analysis of observational data: 35% CHD risk reduction in women using hormone therapy • Lipid Effects:  LDL Cholesterol  Lipoprotein (a)  HDL Cholesterol • Metabolic Effects:  Fasting glucose  Fasting insulin levels • Fibrinolytic Effects:  tissue plasminogen activator,  plasminogen-activator inhibitor 1 Sources: Grady 1992, Mendelsohn 1999, Espeland 1998

5. 15 Estrogen-Progestin Placebo 10 5 1 0 2 3 4 5 HERS: Cumulative Incidence of CHD Events Incidence, % (113) (2763) (2631) (2506) (2392) (1435) Follow-up, yrs (No. at Risk) Source: Adapted from Hulley 1998

6. Women’s Health Initiative Estrogen and Progestin Arm: Absolute Excess Risk • Excess CHD events: 7/10,000 woman-years • Excess stroke events : 8/10,000 woman-years • Excess pulmonary emboli: 8/10,000 woman-years • Excess invasive breast cancer: 8/10,000 woman-years Source: Writing Group for the WHI Investigators 2002

7. Women’s Health Initiative Estrogen and Progestin Arm: Absolute Benefits • Fewer colorectal cancers: 6/10,000 woman-years • Fewer hip fractures: 5/10,000 woman-years Source: Writing Group for the WHI Investigators 2002

8. Women’s Health Initiative: Estrogen Alone in Postmenopausal Women Compared to Placebo: Major Clinical Outcomes * * * P < .05 Favors Treatment Favors Placebo Source: Adapted from WHI Steering Committee 2004

9. HT Risk-Benefit Balance: 2004 Risks DVT/PE Gallbladder Disease Breast Cancer Breast/Bleeding Side Effects CHD Stroke Dementia Pancreatitis ?Ovarian Cancer Benefits Vasomotor Symptoms Osteoporosis Vaginal Atrophy Colon Cancer Skin Preservation Depression Source: ACOG Task Force for Hormone Therapy 2004

10. Raloxifene Use for the Heart (RUTH) Trial: Primary and Secondary CVD Outcomes * * p < .05 Source: Adapted from Barrett Connor 2006

11. Interventions that are not useful/effective and may be harmful for the prevention of heart disease • Hormone therapy and selective estrogen-receptor modulators (SERMs) should not be used for the primary or secondary prevention of CVD Source: Mosca 2007

12. Menopausal Hormone Therapy, SERMs and CVD: Summary of Major Randomized Trials • Use of estrogen plus progestin associated with a small but significant risk of CHD and stroke • Use of estrogen without progestin associated with a small but significant risk of stroke • Use of all hormone preparations should be limited to short term menopausal symptom relief • Use of a selective estrogen receptor modulator (raloxifene) does not affect risk of CHD or stroke, but is associated with an increased risk of fatal stroke Source: Hulley 1998, Rossouw 2002, Anderson 2004, Barrett-Connor 2006