WHI Overview of WHI Overview of Principal ResultsPrincipal Results

Vanessa M. Barnabei, MD, Vanessa M. Barnabei, MD, PhDPhD

Medical College of WisconsinMedical College of Wisconsin

Obstetrics and GynecologyObstetrics and Gynecology

Cardiovascular DiseaseCardiovascular DiseaseE+PE+P

85068506PLPL

81028102HRHR EE

53105310PLPL

54295429HRHR

CHDCHD

(total)(total)188188 147147 1.241.24 177177 199199 0.910.91

CHD CHD DeathDeath

3939 3434 1.101.10 5454 5959 0.940.94

StrokStrokee

(total)(total)

127127 8585 1.411.41 158158 118118 1.391.39

FatalFatal 1616 1313 1.201.20 1515 1414 1.131.13

Non-Non-fatalfatal

9494 5959 1.501.50 114114 8585 1.391.39

Venous ThromboembolismVenous Thromboembolism

E+PE+P

85068506PLPL

81028102HRHR EE

53105310PLPL

54295429HRHR

VTEVTE

(total(total))

151151 6767 2.112.11 101101 7878 1.331.33

DVTDVT 118118 5252 2.072.07 7777 5454 1.471.47

PEPE 7070 3131 2.132.13 4848 3737 1.341.34

Breast CancerBreast Cancer

E+PE+P

85068506PLPL

81028102HRHR EE

53105310PLPL

54295429HRHR

TotalTotal 245245 185185 1.241.24

In situIn situ 4747 3737 1.181.18

InvasivInvasivee

166166 124124 1.261.26 9494 124124 0.70.777

FractureFracture

E+PE+P

85068506PLPL

81028102HRHR EE

53153100

PLPL

54295429HRHR

Hip FxHip Fx 4444 6262 0.660.66 3838 6464 0.610.61

VertebrVertebral Fxal Fx

4141 6060 0.660.66 3939 6464 0.620.62

Total Total 650650 788788 0.760.76 503503 724724 0.700.70

Quality of LifeQuality of Life

Symptom Relief: Effects of E+PSymptom Relief: Effects of E+P

• In women symptomatic at baseline:In women symptomatic at baseline:– Improvement in:Improvement in:

•Hot flashesHot flashes

•Night sweatsNight sweats

•Vaginal drynessVaginal dryness

• Joint pain/stiffnessJoint pain/stiffness

•General aches and painsGeneral aches and pains

• Younger, thinner women got the most Younger, thinner women got the most relief from vasomotor symptomsrelief from vasomotor symptoms

Side Effects of E+PSide Effects of E+P

• In women asymptomatic at baseline:In women asymptomatic at baseline:– Worsening of:Worsening of:

•Breast tendernessBreast tenderness

•Vaginal dischargeVaginal discharge

•Vaginal irritationVaginal irritation

•HeadacheHeadache

• Older, thinner women more likely to Older, thinner women more likely to develop breast tendernessdevelop breast tenderness

Protective Effects of E+PProtective Effects of E+P

• In women asymptomatic at baseline:In women asymptomatic at baseline:– Protection from:Protection from:

•Hot flashes/night sweatsHot flashes/night sweats•Vaginal drynessVaginal dryness• Joint pain/stiffnessJoint pain/stiffness•General aches and painsGeneral aches and pains•Lower back painLower back pain•Neck painNeck pain

• Protective effect on joint symptoms Protective effect on joint symptoms seen in all age groupsseen in all age groups

Bleeding: Effects of E+PBleeding: Effects of E+P

• E+P:E+P:– At 6 weeks: 42.5%At 6 weeks: 42.5%– At 6 months: 54.0%At 6 months: 54.0%– At 5 years: 13.1%At 5 years: 13.1%

• Women who were older, further from Women who were older, further from LMP, thinner and never/past HRT LMP, thinner and never/past HRT users were more likely to report users were more likely to report bleedingbleeding

Summary: Symptoms (E+P)Summary: Symptoms (E+P)

• Vasomotor symptoms common in Vasomotor symptoms common in younger postmenopausal womenyounger postmenopausal women

• Musculoskeletal symptoms very Musculoskeletal symptoms very common in all age groupscommon in all age groups

• E+P relieved and prevented vasomotor E+P relieved and prevented vasomotor and musculoskeletal symptomsand musculoskeletal symptoms

• Women most likely to benefit from E+P Women most likely to benefit from E+P are younger, symptomatic womenare younger, symptomatic women

Effects of Estrogen-Alone and Placebo on Disease Rates

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Effects of Estrogen-Plus-Progestin and Placebo on Disease Rates

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WHI E+P and E-Alone Trials: Absolute (annualized) Risk

Risks Benefits

Risk BenefitRisk? Benefit?

WHI PublicationsWHI Publications

• Almost 400 manuscripts published or Almost 400 manuscripts published or in various stages of preparation in various stages of preparation through Publications committeethrough Publications committee

• Over 200 ancillary studies approved, Over 200 ancillary studies approved, most with outside fundingmost with outside funding

• Large database available with Large database available with demographic, reproductive, health demographic, reproductive, health informationinformation

BiomarkersBiomarkers

• Many ancillary studies utilize blood, Many ancillary studies utilize blood, serum, and DNA available through serum, and DNA available through WHIWHI

• Available analytes include:Available analytes include:– Hormones and receptorsHormones and receptors– Growth factors and receptorsGrowth factors and receptors– LipidsLipids– Vitamins, etc. Vitamins, etc. – DNA such as CYP, MTHFR, TNFDNA such as CYP, MTHFR, TNF

Ancillary Studies-ExamplesAncillary Studies-Examples

• ““Hormones and biomarkers Hormones and biomarkers predicting stroke in women” (OS)predicting stroke in women” (OS)

• ““Biochemical and genetic Biochemical and genetic determinants of fracture in determinants of fracture in postmenopausal women” (OS)postmenopausal women” (OS)

• ““Decision-making about cancer Decision-making about cancer screening among older women” (HT-screening among older women” (HT-CT)CT)

• ““Prevalence and natural history of Prevalence and natural history of autoimmune thyroid disease in autoimmune thyroid disease in postmenopausal women” (OS)postmenopausal women” (OS)

Ancillary StudiesAncillary Studies

• Complete list of studies, biomarkers Complete list of studies, biomarkers available from WHI investigatorsavailable from WHI investigators

• WHI investigator must be a WHI investigator must be a co-investigatorco-investigator

• All proposals for ancillary studies All proposals for ancillary studies must be approved by Publications must be approved by Publications and Proposals Committee of WHIand Proposals Committee of WHI