Further Findings of the Womens Health Initiative of Risks and Benefits of Estrogen plus Progestin in

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Further Findings of the Womens Health Initiative
of Risks and Benefits of Estrogen plus Progestin
in HealthyPostmenopausal Women
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WHI EstrogenProgestin Trial

• History
• Benefit
• Primary Outcome - CHD
• Secondary Outcome Hip Fracture
• Adverse
• Primary Outcome Breast Cancer
• Secondary Outcome Other Cancers

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WHI EstrogenProgestin Trial

• History
• Recruitment 161,809 1993-1998
• Termination E P trial by DSMB - 2002
• Termination E-alone trial by NIH - 2004

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Womens Health Initiative Trial of Estrogen
Progestin

• Methods

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WHI Hormone Program Study Population Inclusion
criteria

• Age 50-79 at baseline
• Post menopausal, defined as
• No bleeding for gt6 months (gt12 months for 50-54
  years old)
• Current / prior use of menopausal hormones
• Post hysterectomy with symptoms
• Likely to reside in the clinic area for 3 years
• Willing to provide written informed consent
• Willing to take placebo for 8.5 years

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WHI Hormone Program Design
Conjugated equine estrogen (CEE) 0.625 mg/d
YES
N 10,739
Placebo
Hysterectomy
CEE 0.625 mg/d medroxyprogesterone acetate
(MDA) 2.5 mg/d
NO
N 16,608
Placebo
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WHI EstrogenProgestin Trial Outcome
Ascertainment

• Initial report of all hospitalizations and
  selected other events by self-administered
  questionnaire
• If events reported, more detailed information
  collected by structured questionnaire
• Medical records obtained
• Adjudication by local physicians who were
  centrally trained and blinded to treatment
  assignments and participants symptoms
• Central adjudication of key outcomes in progress

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Womens Health Initiative Trial of Estrogen
Progestin

• Results

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Attributable Risk Summary

• Excess risk per 10,000 person-years on EP
• 7 more women with CHD
• 8 more women with stroke
• 8 more women with PE
• 8 more women with breast cancer
• Risk reduction per 10,000 person-years on EP
• 6 fewer colorectal cancer
• 5 fewer hip fractures
• Summary 19 additional monitored events per
  10,000 person years on EP

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• WHI
• CORONARY
• HEART
• DISEASE

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Coronary Heart Disease
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• WHI
• FRACTURES

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WHI COLORECTAL CANCER
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Characteristics of Colorectal Cancer, by
Treatment Group
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• WHI
• DEMENTIA

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WHIMS Neurological Evaluation

• Phase Tests
• Modified Mini Mental State Exam
• Expanded Neuropsychological Battery
• Interviews
• Geriatric Depression Scale
• Questions Participant, Informant
• Physical Exams - by Specialist
• Clarify Mental State
• Laboratory Tests
• 1. CT Brain Without Contrast
• 2. Blood Tests
• WHIMS JAMA 2892651, 2003

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• WHI
• BREAST
• CANCER

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Characteristics of Invasive Breast Cancer by
Treatment Group
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Mammogram FindingsTreatment Group

• Baseline Most Severe Dx
• E P Placebo E P Placebo
• Negative 4125 4118 1359 1631
• Benign 2807 2810 4294 4590
• Abnormal 384 363 2601 1677
• P lt .001
• WHI JAMA 2892673, 2003.

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• WHI
• GYNECOLOGICAL
• CANCER

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Gynecological Cancer

• Type E P Placebo HR
• (95 CI)
• Ovarian 20 12 1.58
  (0.77-3.24)
• Endometrial 27 31 0.81 (0.48-1.36)
• Cervix 8 5 1.44 (0.47-4.42)
• WHI JAMA 2901739, 2003

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Endometrial Surveillance

• E P Placebo P
• Endometrial Biopsy 2569 439 lt .001
• Multiple Biopsies 979 72 lt .001
• Ultrasound (US) 1089 331 lt .001
• Multiple US 299 60 lt .001
• WHI JAMA 2901739, 2003

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