Cardiovascular Disease in WomenModule 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 BenefitsCHD Osteoporosis Vasomotor SymptomsGU SymptomsSkin 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)

Inc i

den

ce

, %

0 2 3 4 51

10

5

15

(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

0.61

0.77

0.91

1.04

1.08

1.39

0 0.5 1 1.5 2

Stroke

Colorectal Cancer

Total Mortality

CHD

Breast Cancer

Hip Fracture

Relative Risk Compared to Placebo

*

* P < .05*

Favors Treatment Favors Placebo

Source: Adapted from WHI Steering Committee 2004

HT Risk-Benefit Balance: 2004

BenefitsVasomotor SymptomsOsteoporosisVaginal AtrophyColon CancerSkin PreservationDepression

RisksDVT/PEGallbladder DiseaseBreast CancerBreast/Bleeding Side EffectsCHDStrokeDementiaPancreatitis?Ovarian Cancer

Source: ACOG Task Force for Hormone Therapy 2004

Raloxifene Use for the Heart (RUTH) Trial: Primary and Secondary CVD Outcomes

0

100

200

300

400

500

600

CHD events Fatal CHD Stroke Fatal Stroke

RaloxifenePlacebo

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