** Women’s Health Initiative (WHI) (USA)

Field Names
Records
Coordinating Country
United States

(The Fred Hutchinson Cancer Research Center in Seattle, WA served as the WHI Clinical Coordinating Center for data collection, management, and analysis)

Region

USA

The WHI clinical trial and observational study was conducted at 40 clinical centers in 24 states and the District of Columbia:
Alabama (Birmingham)
Arizona (Tucson)
California (Los Angeles, Oakland, Orange County, Sacramento, San Diego, Stanford, Torrance)
Florida (Gainesville, Miami)
Georgia (Atlanta)
Hawaii (Honolulu)
Illinois (Chicago)
Iowa (Iowa City)
Massachusetts (Boston, Worcester)
Michigan (Detroit)
Minnesotta (Minneapolis)
Nevada (Reno)
New Jersey (Newark)
New York (Bronx, Buffalo, Stony Brook)
North Carolina (Chapel Hill, Greensboro)
Ohio (Cincinnati, Columbus)
Oregon (Portland)
Pennsylvania (Pittsburgh)
Rhode Island (Pawtucket)
Tennessee (Memphis)
Texas (San Antonio, Houston)
Washington (Seattle)
Wisconsin (Madison, Milwaukee)

Brief Database Description

** NOTE: In contrast to our usual policy, this profile has not been reviewed by the DBM. We are continuing to seek further information on the fields with missing data. The original Women's Health Initiative (WHI) was a 15-year national health study established in 1991 by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI) that focused on strategies for preventing heart disease, breast and colorectal cancer, and osteoporosis in postmenopausal women. The Fred Hutchinson Cancer Research Center in Seattle, WA serves as the WHI Clinical Coordinating Center for data collection, management, and analysis of the WHI. The WHI Clinical Trial (CT) and Observational Study (OS) were conducted at 40 Clinical Centers nationwide. Recruitment began in September 1993 and continued through October 1998 for the CT; the OS enrollment continued through December 1998. Close-out of the WHI CT occurred between October 2004 and March 2005. Overall, the WHI involved 161,808 women aged 50-79 from 40 clinical centers as part of three components: the randomized CT, the OS, and a Community Prevention Study (CPS). The WHI CT and OS attempted to address many of the inequities in women's health research and provide practical information to women and their physicians about hormone therapy, dietary patterns, and calcium/vitamin D supplements, and their effects on the prevention of heart disease, cancer, and osteoporosis. The WHI CPS was a 5-year cooperative venture with the Centers for Disease Control and Prevention (CDC) to develop community-based public health interventions models which would enhance adoption of healthful behaviors in women aged 40 and over. WHI Extension Studies have continued follow-up of consenting participants, the first consenting participants from each of the original WHI study components for an additional five years (2005-2010) of follow-up, and the second consenting pariticpants from the first Extension Study for an additional five years (2010-2015). Annual updates on health outcomes are collected by mail from the participants enrolled in each Extension Study. There have also been other ancilliary studies, such as the Long Life Study using a subpopulation of the WHI cohort.

 
In 2010, the Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) dataset was released on dbGAP (database of Genotypes and Phenotypes). The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program.

The WHI Clinical Trials (CT) (N=68,132) include three overlapping components, each a randomized controlled comparison among women who were postmenopausal and aged 50-79 at randomization:
- Hormone Therapy Trial (HT) (27,347)
- Dietary Modification Trial (DM) (48,835)
- Calcium/Vitamin D Supplementation Trial (CaD) (36,282)
Eligible women could be randomized into one, two, or all three of the CT components. Women who were ineligible or unwilling to join the CT were invited to join the Observational Study (OS) (N=93,676). Recruitment, follow-up, and analysis for the OS was concurrent with the CT. The health of OS participants was tracked over an average of eight years, but up to 12 years. Women who joined this study filled out periodic health forms and also visited the clinic three years after enrollment. OS participants were not required to take any medication or change their health habits. It did, however, follow a woman's health over a long period of time.

Database Type
Longitudinal Population Database
- Drug and Diagnosis Data
Large Clinical Trial Database
Tissue/Blood and Genomic/Pharmacogenetic Database

 
Drug and Diagnosis Data are available for outpatients only.
The WHI CT was a long-term randomized clinical trial with multiple interventions:
- Dietary Modification (DM) - The 48,835 women who joined the DM were randomly assigned to either a sustained low-fat eating pattern (40% of the women) or their usual, self-selected dietary behavior (60%).
- Hormone Therapy (HT) - Women in the HT were randomized within one of two double-blind trials, Estrogen plus Progestin, or Estrogen-Alone, depending on hysterectomy status at baseline. In the Estrogen plus Progestin trial, 16,608 women with an intact uterus at baseline were randomized 1:1 to take either combined Estrogen plus Progestin or placebo study pills. In the Estrogen-Alone trial, 10,739 women who were post-hysterectomy at baseline were randomized 1:1 to take either unopposed estrogen or placebo.
- Calcium/Vitamin D (CaD) - Women participating in either DM or HT were invited to join the CaD 12 to 24 months after randomization. The 36,282 women eligible for the double-blind CaD trial were randomized 1:1 to take study pills containing calcium/vitamin D or a placebo.

The WHI OS is a non-interventional cohort study with regular follow-up periods. OS study participants are contacted annually by mail to obtain updates of their medical histories and selected exposure data. At about 3 years after enrollment, all OS participants are invited to a clinic follow-up visit to update selected baseline data, to obtain additional risk factor data, and to collect a blood specimen. A 1% sample of OS participants are asked to return to the clinic between 1 and 3 months after their baseline and 3-year visits to participate in a reliability substudy, at which time blood will be drawn and the measurement of selected data items that are prone to measurement error are repeated.

The WHI holds a large repository of biological specimens that are available for ancillary study investigations. WHI will make available baseline and Year 3 serum, citrate plasma, EDTA plasma samples, and DNA for use by investigators who successfully compete for the Broad Agency Announcement (BAA).

Database Source
Case Report Forms

Survey Data
Other
(Data were collected from participants via the following:
(1) Self-administered forms;
(2) Interviews: Data on participant’s past hormone use at baseline, current medications, and current supplements were collected by in-person interviews. In addition, management and safety data for Hormone Therapy (HT) and Calcium and Vitamin D (CaD) participants were collected through by interviews at annual visits and often by phone interviews for semi-annual contacts; and
(3) Clinical measurements.
(4) Genotyping data: In 2010, the WHI SNP Health Association Resource (SHARe) dataset was released on dbGAP. The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the HI program.)

Frequency of Data Collection
Other

(Data collection varied for each study in the CT and OS components, and also varied by type of data being collected. For example, the Medical History Update forms were completed semiannually for all CT participants and annually for all OS participants.

Data collection at follow-up for general CT (differs for specific trials): At years 1, 3, 6 and 9, CT participants will also be asked to bring in all their medications and vitamin supplements for an updated inventory, and ECGS will be obtained at years 3, 6, and 9. At the annual visit, all CT participants will have their questionnaires reviewed for potential outcomes and will have a brief physical exam. Additional measures will be obtained at the first annual visit and at years 3, 6, and 9, with some elements restricted to a subsample.

Data collection at follow-up for OS: Three years after enrollment into the study, all OS participants were invited to a follow-up clinic visit. Before this visit they were mailed a packet of questionnaires on health habits, medical history and outcomes, as well as psychosocial and food frequency questionnaires. They were asked to bring in their current medications and supplements. At the clinic visit, they will have blood drawn, their medications and supplements will be recorded, and the following measurements will be taken: height, weight, waist and hip measurements, and blood pressure. At osteoporosis centers, bone densitometry studies and urine samples were completed for all OS women every three years.

In the 2005-2010 and 2010-2015 WHI Extension Studies, participants have been followed annually.

For a full listing, select Frequency of Data Collection Table available at: https://cleo.whi.org/about/SitePages/Data%20Collection%20Procedures.aspx)

Frequency of Data Update
Other

(Data for the original WHI and 2005-2010 Extension Study are no longer being updated; database updates for the 2010-2015 WHI Extension Study are ongoing.)

Years Covered
1993 - Present

(The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2015)

Population Type
Outpatient/Non-Institutionalized

Clinical Trial Participants
[All women in WHI were aged 50-79 years and postmenopausal at the time of enrollment. The exclusion criteria varied for each study in the CT and OS components. More details can be obtained in Table 1 of: Hays J et al. The Women's Health Initiative recruitment methods and results. Ann Epidemiol. 2003 Oct;13(9 Suppl):S18-77 (available at: https://cleo.whi.org/about/Baseline%20Monograph/baseline_Recruitment.pdf)]

Patient Type
Outpatient/Non-Institutionalized
Date of Last Update

(The original WHI study period (1993-2005) and the first WHI Extension Study (2005-2010) are now closed. The second WHI Extension Study (2010-2015) is currently ongoing;
This profile was created for the BRIDGE TO DATA site on August 26, 2019.)

Field Names
Records
Database Population Size
<200,000

Overall there were 161,808 participants. The study population for each component is as follows:
CT = 68,132
OS = 93,676
Ext 1 = 115,406 (71.3% of original WHI participants)
Ext 2 = 93,500 (57.8% of original WHI participants)

Active Population Size
<200,000

Currently, the WHI Extension Study 2 is ongoing, and includes 93,500 participants in the database (57.8% of the original study population)

Annual Change in Population
N/A

(Not applicable)

Sample Weights - Extrapolation Factors
No
Final Population Size
N/A

(161,808 is the final total population size of the WHI study; however, with each extension study or substudy, the population size decreases.)

Field Names
Records
Age of Patients at Data Collection
Yes

(Age, Age group, and Age at menopause were collected)

Approximate Percentage of Participants <18 years and those >65 years

<18 years = 0%
>60 years = 66.9%

[50 - 54 yrs N=21,570 (13.3%)
55 - 59 yrs N=31,983 (19.8%)
60 - 69 yrs N=72,588 (44.9%)
70 - 79 yrs N=35,667 (22.0%)
Total: 161,808]

Gender Data
Yes

(Females only)

Percentage of Males/Females

Males = 0%
Females = 100%

Ethnicity / Race Data
Yes

Ethnicity/Race categories include:
American Indian or Alaskan Native N=713 (0.4%)
Asian or Pacific Islander N=4,190 (2.6%)
Black or African-American N=14,618 (9.0%)
Hisplanic/Latino N=6,484 (4.0%)
White (not of Hispanic origin) N=133,541 (82.5%)
Other N=1,849 (1.1%)
Missing N=413 (0.3%)
Total: 161,808

An Addendum form with more specific questions on race/ethenic group was completed by 137,732 participants, which additionally listed various Asian races (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Pacific Islanders (Hawaiian Native, Guamian/Chamorro, Samoan).

Additionally, preferred language (English/Spanish) was also obtained.

Geographic Location

USA

[The WHI clinical trial and observational study was conducted at 40 clinical centers in 24 states and the District of Columbia.
Alabama (Birmingham)
Arizona (Tucson)
California (Los Angeles, Oakland, Orange County, Sacramento, San Diego, Stanford, Torrance)
Florida (Gainesville, Miami)
Georgia (Atlanta)
Hawaii (Honolulu)
Illinois (Chicago)
Iowa (Iowa City)
Massachusetts (Boston, Worcester)
Michigan (Detroit)
Minnesotta (Minneapolis)
Nevada (Reno)
New Jersey (Newark)
New York (Bronx, Buffalo, Stony Brook)
North Carolina (Chapel Hill, Greensboro)
Ohio (Cincinnati, Columbus)
Oregon (Portland)
Pennsylvania (Pittsburgh)
Rhode Island (Pawtucket)
Tennessee (Memphis)
Texas (San Antonio, Houston)
Washington (Seattle)
Wisconsin (Madison, Milwaukee)]

Date of Birth Recorded
Yes

(However, these data are not released to researchers; Instead, age data can be used)

Death Recorded
Yes

Death, Date of death, Cause of death, Method of adjudication for cause of death are all collected in the Report of Death form. All dates in the study cannot be reported directly, including date of death; however, they are converted to 'days from enrollment'.

Availability of death certificate / autopsy information
No
Other Demographic Data
Yes

Socioeconomic data include the following: Education, employment status, and occupation (for participants and participants' partners); marital status; total family income; insurance coverage; service in armed services; direct family members (# siblings, etc.); social support, social integration, social strain, care giving; optimism, negative emotional expressiveness, hostility; daily life items (quality of life; symptoms; life events; depression; sleep disturbance; urinary incontinence; sexual functioning); religious affiliation; state of residence history; US region of birth; parents' birthplace; lived on a farm; age at first paid work; life events, etc.

Field Names
Records
Physician ID
Yes

Captured information includes: Clinical Center ID, Exam by, Report by, and Referral

Physician Specialty
Yes

For diagnosis relating to medical events, an adjudicator code is used (e.g., Report of Cardiovascular Outcomes)

Pharmacy ID
No
Field Names
Records
Diagnosis Data
Yes

All WHI clinical outcomes were identified by self-report on the routine Form 33 - Medical History Update administered semi-annually to Clinical Trial (CT) participants, and annually to Observational Study (OS) participants. Those participants who reported a potential WHI-defined outcome were then contacted by mail or phone and a Form 33D – Medical History Update (Detail) - was completed to obtain more specific information on newly diagnosed health conditions or recent procedures.

Investigation of potential WHI clinical outcomes depended on the type of outcome, the participant’s study component, and whether or not the outcome was a first versus a recurrent event. A documentation set was defined for each type of WHI clinical outcome, and these medical records were used for adjudication.

The following were the outcomes of interest:
- Cardiovascular (Coronary heart disease, Stroke, Congestive heart failure, Angina, Peripheral vascular disease, Carotid artery disease, Coronary revascularization);
- Cancer (Breast cancer, Endometrial cancer, Colorectal cancer, Ovarian cancer, Other cancers, Total cancers);
- Fractures (Hip, Other fractures); and
- Other (Pulmonary embolism, Deep vein thrombosis, Diabetes Mellitus requiring therapy, Death from any cause).

Additionally, reproductive history, quality of life data, and cognitive assessments were also collected.

Diagnoses Coded
ICD-9-CM

ICD-O-2
Other
[Diagnoses are recorded as full-text or questionnaire responses. Diagnoses are also obtained from hospital discharge records by physicians at the clinic centers, and recorded as ICD-9-CM codes. During adjudication, cancer diagnoses were recorded using both ICD-O-2 and SEER EOD (Extend of Disease).]

Diagnoses: Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2015]

Diagnoses: Maximum Number of Codes Allowed
Varies
Physical Examination Findings
Yes

Physical measurements are/were noted (height, weight, blood pressure, heart rate, waist and hip circumference)

Birth Defect Data
No

There are no specific questions on birth defects. However, the following related information is captured:

- Gyenocological and pregnancy data collected include: age at menarche, history of menstrual irregularity and amenorrhea, history of menopausal symptoms, history of pregnancy, pregnancy outcomes, infertility; history of breast feeding, and history of gynecologic & breast surgeries.

- Birth-related questions include: birth weight, birth status, and breast feeding at birth.

Cancer Data
Yes

Data on the following cancers were specifically obtained: Breast cancer, Endometrial cancer, Colorectal cancer, Ovarian cancer, Other cancers, and Total cancers. As with other outcomes of interest, the cancers developing after study start date were adjudicated by a clinician. Additional data included confirmation method (e.g., histology), subclassification, reporting source, SEER summary stage, and tumor marker assay (e.g., estrogen receptor, progesterone receptor, HER-2/Neu)

Infectious Disease Data
No
Environmental Exposures
Yes

Data on non-medical exposures include: history of insecticide exposure; history of living with pets; history of computer use (frequency, duration); history of hand-held hair dryer use (frequency, duration); history of the use of powders in genital area or on sanitary napkins; history of diaphragm use; history of electric blanket use; exposure to foods and beverages (e.g., artificial sweeteners); sunlight exposure; video and video display terminal exposure; lived with smoker as a child; use of hair dyes; lived on a farm, etc.

Behavioral Data Elements
Yes

Behavioral data include: Personal habits (coffee/tea consumption, smoking history, alcohol history, weight change, special diets, history of physical activity and exercise (frequency, duration, hours sitting, hours doing heavy chores); Thoughts and feelings (social support, social integration, care giving, social strain, optimism, negative emotional expressivenes, hostility); Daily life items (quality of life, symptoms, life events, depression, sleep disturbance, urinary incontinence, sexual functioning); Cognitive assessment (expanded mini mental status examination); Food/Beverage consumption (food frequency); Diet/Nutritions (e.g., recent use of fats or oils, recent wine consumption); Care-giving responsibilities; sleep patterns, etc.

Field Names
Records
Procedure Data
Yes

These data are self-reported as well as collected from the clinical center physicians who obtain patient hospital discharge records

Procedures Coded
ICD-9-CM
Other

[Procedures that are self-reported are recorded in full-text, and those obtained from hospital discharge records are provided as ICD-9-CM procedure codes (if available)]

Number of Procedures Coded
N/A

Varies

Procedure Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2015]

Laboratory Information
Yes

Laboratory tests include: Pelvic exams, endometrial aspiration, transvaginal uterine aspiration, clinical breast exam, mammogram, bone density scan, electrocardiogram (ECG), functional status (e.g., grip strength), pap smear, blood tests, urine tests, tests done for diagnosis adjudication (e.g., pathology/histology for cancers), biomarker tests (glucose, insulin, lipids, CRP, and creatinine), and genotyping data (limited and de-identified), biospecimen collection.

Field Names
Records
Drug Data
Yes: Prescription & OTC

Other
A list of current medications and supplements used are recorded, including duration of use (days and years). Some medications and supplements are of particular interest to the study initiatives and have questionnaires specific to them, e.g., hormone replacement therapy, use of supplements, and medications for breast health.

Drug Date Parameters
1993 - Present

[The periods of study are as follows:
WHI (original): 1993-2005
WHI Extension Study (first extension): 2005-2010
WHI Extension Study (second extension): 2010-2015]

Drug Regimen & Route
No

However, this information can be obtained from the NDC data

Drug Manufacturer
No

However, this information can be obtained from the NDC data

Drug Dosage
No
Drug Days Supply
Yes

In some cases, the number of pills/week are captured

Drug Coding System: Maximum Number
Unlimited

This information also varies based on the specific questionnaire

Drug Coding System: Primary
NDC

(All current medications are recorded using NDC)

Drug Coding System: Other
Other

[When possible, each reported current medication is also classified using the NDC's directory of the therapeutic drug class(es), and codes are assigned to medications. Additionally, the breast health medication forms contain a drug inventory list specific to breast cancer medications (e.g., tamoxifen, raloxifene, toremifene, etc.)]

Drug Generic Name
Yes
Drug Additional Information
Yes

Additional drug data captured are: Adherence to study medications (intervention in WHI CT), changes in medication that occur, and reason for medication change (e.g., intolerance, side effects, barriers due to insurance coverage, physician prescribing, inconvenience, etc.).

Field Names
Records
Biobank Type
N/A
Human Specimen
N/A
Blood Type
N/A
Biomarkers
N/A
Patient ID
N/A
Number of Samples
N/A
Frequency of Sample Collection
N/A
Pre-diagnostic Sample Collection
N/A
Post-treatment Sample Collection
N/A
Method of Sample Collection
N/A
Age at Sample Collection
N/A
Date of Sample Collection
N/A
Reason for Sample Collection
N/A
Method of Sample Storage
N/A
Length of Sample Storage
N/A
Pathology
N/A
DNA Isolation
N/A
RNA Isolation
N/A
Cell Culture
N/A
Genetic Testing
N/A
Access for Research: Specimens
N/A
Access for Research: Genetic Data
N/A
Access for Research: Epidemiologic Data
N/A
Quality Assurance Procedures
N/A
Family History
N/A
Medical History
N/A
Biobank Linkage
N/A
Field Names
Records
Type of Genetic Database
GWAS database

 

The Observational Study (OS) of the WHI examines the relationship between lifestyle, environmental, medical and molecular risk factors and specific measures of health or disease outcomes. This component involves tracking the medical history and health habits of 93,676 women not participating in the clinical trial. Recruitment for the observational study was completed in 1998 and participants were followed annually for 8 to 12 years.

The original protocol allowed for follow-up until March 2005, after which participants were invited to enroll in the first WHI Extension Study for follow-up through 2010. Participants were invited again to participate in the second WHI Extension Study with continued follow up from 2010 to 2015. As of March 31, 2011 there were 93,122 women enrolled in the second extension. As part of the second Extension, 80+ year old women were asked to consent to an In Person Visit at their homes during which additional blood samples were collected and various measurements were taken (such as blood pressure, height, weight, waist circumference, grip strength, etc.).

Genetic and phenotypic data from WHI sub-studies re routinely submitted to the database of genotypes and phenotypes (dB Gap). Individual-level genetic and phenotype data are available for 64,291 study subjects.

Source of Genetic Data
Clinical trial data

 

This WHI dB Gap Cohort release of the WHI baseline and follow-up data includes data collected on study forms, outcomes, results from blood analyses, and computed variables for WHI participants who have been selected for specific studies where genotype data will be submitted to dB Gap.

The WHI study ended March 31, 2005, and the closeout date for data collection was April 8, 2005. Participants consenting to join the first WHI Extension Study were followed through September 30, 2010, primarily for outcomes data collection. Those consenting to the second WHI Extension Study continue to be followed for outcomes data collection. This data release includes data through the end of the first WHI Extension Study.

The following clinical sub-studies have reported genotype, expression, and other molecular data from the WHI cohort:
phs000386 WHI SHARe
phs000281 GO-ESP WHISP
phs000315 WHI GARNET
phs000503 WHISE
phs000227 PAGE WHI
phs000675 WHIMS+
phs000746 WHI Harmonized and Imputed GWAS

Specimen Genotyped
Yes

(Buffy coat DNA extracted from blood samples)

Tissue Form
Other

(DNA is extracted from buffy coat blood. Buffy coats were removed from the spun EDTA and citrate blood collection tubes and placed in 1.8 ml freezer vials.)

Genetic Template
DNA
Gene-Drug Response
Yes

Data on current medications and current supplements (daily nutrient intake from multivitamins and single supplements) are available. These data can be linked by subject ID with genetic data.

Gene-Disease Relationship
Yes

The current release of outcomes data includes centrally verified, locally verified and self-reported outcomes collected through the first WHI Extension Study for clinical trial, observational study, and Calcium and Vitamin D study. The outcomes data sets include all WHI participants, and the first occurrence of outcomes since the beginning of WHI. Outcomes that are adjudicated or laboratory-tested are:
CARDIOVASCULAR:
- MI
- Stroke
- Congestive heart failure
- Angina
- Peripheral artery disease (PAD)
- Carotid artery disease (CAD)
- Coronary revascularization (PTCA/CABG)
- TIA
CANCER:
- Breast cancer
- Endometrial cancer
- Colorectal cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lung
- Lymphoma, Hodgkin's
- Lymphoma, Non-Hodgkin's
- Pancreas
- Other cancers
FRACTURES:
- Hip
- Non-hip fractures
OTHER:
- Pulmonary embolism
- Deep vein thrombosis
- Hysterectomy
- Death from any cause

Outcomes which are self-reported are:
- Cataracts
- Colorectal polyps/adenomas
- Dementia, Alzheimer's
- Diabetes diagnosis, ever
- Fractures (non-hip)
- Gallbladder disease/stones
- Glaucoma
- Kidney/bladder stones
- Macular degeneration
- Osteoarthritis
- Osteoporosis
- Parkinson's disease
- Rheumatoid arthritis
- SLE

Exams/Procedures:
- Barium enema X-ray
- Blood in stool
- Blood pressure
- Bone density scan
- Breast biopsy/aspiration
- Breast exam
- Breast exam, other (MRI/ultrasound)
- Cholesterol
- D&C
- ECG
- Endometrial biopsy
- Eye exam
- Flex sig/colonoscopy
- Hysterectomy
- Mammogram
- PAP smear
- Physical exam
- Rectal exam

Medication/treatments:
- Anxiety pills
- Depression pills/therapy
- Diabetes mellitus requiring therapy
- Diabetes, diet/exercise
- Diabetes, insulin
- Diabetes, pills
- Estrogen pills
- High blood pressure pills
- High cholesterol pills
- Shots for DVT
- Osteoporosis calcium pills
- Osteoporosis non-calcium pills

Gene-Health Outcome Relationship
Yes

Data on hospitalization are captured. These data can be linked by subject ID with genetic data.

Gene-Environment Response
Yes

Data are captured on diet, lifestyle, activities, personal habits (smoking, coffee, alcohol), social/personal support and satisfaction. These data can be linked by subject ID with genetic data.

Method of Imputing Genetic Data
N/A
Genetic Variant Identification
Other

(Gap accession number, BioSample number, Sequence Read Archive (SRA) number are available in the publicly available dB Gap records. The full genetic dataset (restricted access) includes dbSNP accession / rsID.)

Genetic Data Level
Individual
Aggregate - by study population
Genotyping Method
Yes

Both, the genotyping method (PCR, Illumina array, Affymatrix array) and genotype data (SNP or whole exome) are indicated

Method of Genetic Variant Filtering
N/A

(Not applicable)

Haplotypes
Yes

(in SHARe study)

Haplogroups
No
Variable Number of Tandem Repeats (VNTR)
No

(However, may obtain via linkage to dbSNP database)

Single Nucleotide Polymorphisms (SNPs)
Yes

Linked to the dbSNP database available as SNP accession / rsID

Variant Type
SNPs
Variant Class
No
Mutation Indicated
No
Position
Yes
Amino Acid Change
No
Genotype / Polymorphism
Yes

(Also available via linkage to dbSNP database)

Allele Frequency
Yes

Nucleotide substitution (e.g., C/T)

Linkage Disequilibrium (r²)
Yes
Noncarriers Indicated
Yes
Association Statistics
No

The database does not report association statistics, but individual GWAS studies included statistical analyses, often reporting the OR with respect to phenotype(s) of interest.

Genetic Relatedness Pairing
Yes

(Varied from study to study. For example, in SHARe, genetic relatedness among subjects within the same ethnicity was examined using pair-wise identity-by-descent (IBD) estimation.)

Data Sharing: Genetic Data
Yes, access to genetic data for epidemiologic research only is available

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WHI participants have been included in multiple genome-wide, sequencing, exome-wide, and other genotyping efforts. The distribution of WHI genetic data has historically been handled through a 3rd party (dB Gap). To promote collaborative research with existing WHI principal investigators, and at the request of the NHLBI project office, WHI has added a direct means to access WHI genetic data. Access to genetic data is limited to WHI Principal Investigators, pending approval.

Space needed for the whole set of compressed imputed GWAS data is 2 terabytes. Data are broken into files by study and chromosome, but generally not further (smaller subsets of SNPs will not be extracted for Investigators). Data must be downloaded within 7 days, and can only be downloaded 1 time using the link (for security purposes) in the email sent by WHI staff.

Access for Research
No, access to specimen/genetic data is not allowed
Genetic Data Linkage
N/A

(Not applicable)

Description of Genetic Data Linkage
In 2010, the Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) dataset was released on dbGAP. The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program.
Field Names
Records
Cost Data
No
Cost Denomination
N/A

(Not applicable)

Type of Cost Data
N/A

(Not applicable)

Description of Surrogate Link
N/A

(Not applicable)

Field Names
Records
Data Validation Against Original Source
Yes

For WHI clinical outcomes of interest, data were ascertained by self-report on the routine Form 33 - Medical History Update - administered semi-annually to Clinical Trial (CT) participants and annually to Observational Study (OS) participants. Those participants who reported a potential WHI-defined outcome were then contacted by mail or phone and a Form 33D – Medical History Update (Detail) was completed to obtain more specific information on newly diagnosed health conditions or recent procedures. Investigation of potential WHI clinical outcomes depended on the type of outcome, the participant’s study component, and whether or not the outcome was a first versus a recurrent event. A documentation set was defined for each type of WHI clinical outcome, and these medical records were used for adjudication.

Local Adjudication - Based on specific adjudication criteria, a physician adjudicator at the local Clinical Center either confirmed or denied a potential clinical outcome. Data on confirmed WHI outcomes were entered on outcomes-specific forms for cardiovascular disease, cancer, fracture, hysterectomy, venous thromboembolic disease, as well as hospitalizations and deaths.

Central Adjudication - WHI Clinical Centers were asked to send selected locally adjudicated case packets to the Clinical Coordinating Center for central adjudication, depending on the type of outcome and the participant’s study component. Centrally-trained cardiovascular physician adjudicators (and neurologists, in the case of stroke outcomes) reviewed and adjudicated cardiovascular and death outcomes. The five primary cancers (breast, colon, rectum, endometrium, and ovary) were coded centrally by tumor registry coders. All hip fractures were centrally adjudicated at the WHI Bone Density Center.

Access to Medical Records
No
Linkage to Other Databases
Yes
Brief Description of Linkage Capabilities

In 2010, the Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) dataset was released on dbGAP. The dataset includes extensive phenotypic and genotypic data on 12,008 African American and Hispanic women aged 50-79 enrolled in one or more components of the WHI program. Additionally, Medicare data are currently in the process of being linked to WHI database, but not yet complete.

Field Names
Records
Database Contact Data

Women's Health Initiative Program Office
2 Rockledge Centre
Suite 10018, MS 7936
6701 Rockledge Drive
Bethesda, MD 20892-7936 (U.S. Postal Service)
Bethesda, MD 20817-7936 (Express Mail Service)
USA
Phone: (301) 402-2900
Fax: (301) 480-5158
E-mail: nm9o@nih.gov

** NOTE: In contrast to our usual policy, this profile has not been reviewed by the DBM. We are continuing to seek further information on the fields with missing data.

Alternate Contact

N/A

(Not applicable)

Source of Database Funding
Government
Private

(WHI is sponsored by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI). The Fred Hutchinson Cancer Research Center in Seattle, WA served as the WHI Clinical Coordinating Center for data collection, management, and analysis. The WHI CPS component was a 5-year cooperative venture with the Centers of Disease and Prevention (CDC).)

Sponsoring Government Agency
National Institutes of Health (NIH) - National Heart, Lung, and Blood Institute (NHLBI)
Sponsoring Pharmaceutical Manufacturer

N/A

(Not applicable)

Database Usage Restrictions
Public & Private Access

Access to WHI Datasets is governed by study policy. The current policy requires that in order to gain access to WHI Datasets, you must belong to one of the following categories:
- Current WHI Principal Investigator
- Ancillary Study Principal Investigator
- Former Principal Investigator who was active during the first WHI Extension (2005-2010) for at least one year
- Lead author on an approved paper
Individuals meeting the above criteria who wish to gain access to WHI Datasets must return a signed copy of the WHI Data Distribution Agreement to the WHI CCC.

Questions regarding gaining access to or downloading datasets can be addressed to the WHI Helpdesk (helpdesk@whi.org)

De-identified genotyping data (https://cleo.whi.org/data/Pages/GWAS-Data.aspx) can be requested at the The Biologic Specimen and Data Repository Coordinating Center (BioLINCC) website. Researchers wishing to collaborate with an WHI investigator or interested in applying for future Broad Agency Announcement (BAA) funding must visit the WHI Scientific Resources website (https://cleo.whi.org/researchers/SitePages/Propose%20a%20Study.aspx)

Charge for Database Usage
No
Data Media Format
PDF Files
Other

[Aggregate data are availabe as PDFs at https://cleo.whi.org/data/SitePages/Baseline%20Summary%20Tables.aspx (Baseline Summary Tables), and at https://cleo.whi.org/data/SitePages/Outcomes%20Summary%20Tables.aspx (Outcome Summary Tables).]

Number of Publications Using Database
~2000
References of Studies Using/Describing Database

1. Crawford L, Reeves KW, Luisi N, Balasubramanian R, Sturgeon SR. Perineal powder use and risk of endometrial cancer in postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1673-80.

2. Hartz A, He T, Ross JJ. Risk factors for colon cancer in 150,912 postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1599-605.

3. Chen BH, Brennan K, Goto A, Song Y, Aziz N, You NC, Wellons MF, Manson JE, White DL, Butch AW, Liu S. Sex hormone-binding globulin and risk of clinical diabetes in american black, Hispanic, and asian/pacific islander postmenopausal women. Clin Chem. 2012 Oct;58(10):1457-66.

4. Wang L, Manson JE, Gaziano JM, Liu S, Cochrane B, Cook NR, Ridker PM, Rifai N, Sesso HD. Plasma adiponectin and the risk of hypertension in white and black postmenopausal women. Clin Chem. 2012 Oct;58(10):1438-45.

5. Lemogne C, Consoli SM, Panjo H, Nabi H, Goldberg M, Zins M, Ringa V. Personality and hormone therapy use among postmenopausal women in the GAZEL cohort study. Fertil Steril. 2012 Oct;98(4):929-936.

6. Buhling KJ, von Studnitz FS, Jantke A, Eulenburg C, Mueck AO. Use of hormone therapy by female gynecologists and female partners of male gynecologists in Germany 8 years after the Women's Health Initiative study: results of a survey. Menopause. 2012 Oct;19(10):1088-91.

7. Karsdal MA, Bay-Jensen AC, Henriksen K, Christiansen C. The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet? Menopause Int. 2012 Sep 28. [Epub ahead of print] PubMed PMID:23024184.

8. Orchard TS, Ing SW, Lu B, Belury MA, Johnson K, Wactawski-Wende J, Jackson RD. The association of red blood cell n-3 and n-6 fatty acids to dietary fatty acid intake, bone mineral density and hip fracture risk in the Women's Health Initiative. J Bone Miner Res. 2012 Sep 27. doi: 10.1002/jbmr.1772. [Epub ahead of print] PubMed PMID: 23018646.

9. Rossouw JE, Prentice RL, Manson JE, Aragaki AK, Hsia J, Martin LW, Kuller L, Johnson KC, Eaton C, Jackson R, Trevisan M, Allison M, Hoogeveen RC. Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy. Circulation. 2012 Sep 25;126(13):1577-86.

10. Simon MS, Chlebowski RT, Wactawski-Wende J, Johnson KC, Muskovitz A, Kato I, Young A, Hubbell FA, Prentice RL. Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality. J Clin Oncol. 2012 Sep 24. [Epub ahead of print] PubMed PMID: 23008295.

Database Contact
Database Contact Data

Women's Health Initiative Program Office
2 Rockledge Centre
Suite 10018, MS 7936
6701 Rockledge Drive
Bethesda, MD 20892-7936 (U.S. Postal Service)
Bethesda, MD 20817-7936 (Express Mail Service)
USA
Phone: (301) 402-2900
Fax: (301) 480-5158
E-mail: nm9o@nih.gov

Alternate Contact

N/A

References of Studies Using/Describing Database

1. Crawford L, Reeves KW, Luisi N, Balasubramanian R, Sturgeon SR. Perineal powder use and risk of endometrial cancer in postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1673-80.

2. Hartz A, He T, Ross JJ. Risk factors for colon cancer in 150,912 postmenopausal women. Cancer Causes Control. 2012 Oct;23(10):1599-605.

3. Chen BH, Brennan K, Goto A, Song Y, Aziz N, You NC, Wellons MF, Manson JE, White DL, Butch AW, Liu S. Sex hormone-binding globulin and risk of clinical diabetes in american black, Hispanic, and asian/pacific islander postmenopausal women. Clin Chem. 2012 Oct;58(10):1457-66.

4. Wang L, Manson JE, Gaziano JM, Liu S, Cochrane B, Cook NR, Ridker PM, Rifai N, Sesso HD. Plasma adiponectin and the risk of hypertension in white and black postmenopausal women. Clin Chem. 2012 Oct;58(10):1438-45.

5. Lemogne C, Consoli SM, Panjo H, Nabi H, Goldberg M, Zins M, Ringa V. Personality and hormone therapy use among postmenopausal women in the GAZEL cohort study. Fertil Steril. 2012 Oct;98(4):929-936.

6. Buhling KJ, von Studnitz FS, Jantke A, Eulenburg C, Mueck AO. Use of hormone therapy by female gynecologists and female partners of male gynecologists in Germany 8 years after the Women's Health Initiative study: results of a survey. Menopause. 2012 Oct;19(10):1088-91.

7. Karsdal MA, Bay-Jensen AC, Henriksen K, Christiansen C. The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet? Menopause Int. 2012 Sep 28. [Epub ahead of print] PubMed PMID:23024184.

8. Orchard TS, Ing SW, Lu B, Belury MA, Johnson K, Wactawski-Wende J, Jackson RD. The association of red blood cell n-3 and n-6 fatty acids to dietary fatty acid intake, bone mineral density and hip fracture risk in the Women's Health Initiative. J Bone Miner Res. 2012 Sep 27. doi: 10.1002/jbmr.1772. [Epub ahead of print] PubMed PMID: 23018646.

9. Rossouw JE, Prentice RL, Manson JE, Aragaki AK, Hsia J, Martin LW, Kuller L, Johnson KC, Eaton C, Jackson R, Trevisan M, Allison M, Hoogeveen RC. Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy. Circulation. 2012 Sep 25;126(13):1577-86.

10. Simon MS, Chlebowski RT, Wactawski-Wende J, Johnson KC, Muskovitz A, Kato I, Young A, Hubbell FA, Prentice RL. Estrogen Plus Progestin and Colorectal Cancer Incidence and Mortality. J Clin Oncol. 2012 Sep 24. [Epub ahead of print] PubMed PMID: 23008295.