Cardiovascular Disease in Women Module VI: Update on Menopausal Hormone Therapy and Selective Estrogen Receptor Modulators (SERMs)

Menopausal Hormone Therapy  Observational Data and Assumptions  Randomized Trial Data  Summary of Current Prescribing Guidelines

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

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

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

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

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

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

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

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

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

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