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Women's Health Initiative (WHI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00000611
Recruitment Status : Completed
First Posted : October 28, 1999
Last Update Posted : April 15, 2016
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Cancer Institute (NCI)
National Institute on Aging (NIA)
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary:
To address cardiovascular disease, cancer, and osteoporosis, the most common causes of death, disability, and impaired quality of life in postmenopausal women. The three major components of the WHI are: a randomized controlled clinical trial of hormone replacement therapy (HRT), dietary modification (DM), and calcium/vitamin D supplementation (CaD); an observational study (OS); and a community prevention study (CPS). On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).

Condition or disease Intervention/treatment Phase
Bone Diseases Breast Neoplasms Cardiovascular Diseases Colonic Neoplasms Coronary Disease Heart Diseases Myocardial Ischemia Osteoporosis Postmenopause Drug: hormone replacement therapy Drug: estrogens Drug: progestins Drug: estrogen replacement therapy Behavioral: diet, fat-restricted Drug: calcium Drug: vitamin D Behavioral: dietary supplements Phase 3

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Detailed Description:


Prior to 1991, little research had focused on health issues unique to, or more common for, women. This was especially the case for studies of chronic diseases and their prevention in mature women. These conditions (coronary heart disease, cancer, and osteoporosis) are the leading causes of impairment of quality of life, morbidity, and mortality in post-menopausal United States women. The WHI, mandated by Congress, was established in 1991 by the National Institutes of Health and located in the Office of the Director (OD). The Clinical Coordinating Center for the clinical trial/observational study was funded in September 1992 and the 16 Vanguard Clinical Centers were funded in March 1993. The initial protocol was developed jointly by the Clinical Coordinating Center and the Program Office and was reviewed and approved by the Investigators Committee on April 20, 1993. Additional clinical centers were funded in 1994.

On October 1, 1997, administration of the WHI was transferred to the NHLBI where it is conducted as a consortium effort led by the NHLBI in cooperation with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Cancer Institute (NCI), and the National Institute on Aging (NIA).


As has been described in the objective, the WHI has three major components: a randomized controlled clinical trial, an observational study, and a study of community approaches to developing healthful behaviors. Recruitment for the WHI began in September 1993 and ended in December 1998. Six clinical centers completed recruitment in January 1997. The remaining 34 centers completed recruitment in December 1998.


The clinical trial component consists of three subtrials: the hormone replacement trial, the dietary modification trial, and the calcium /vitamin D supplementation trial. Approximately 27,500 women aged 50 to 79 are participating in the HRT, which tests whether long-term HRT reduces coronary heart disease and fractures without increasing breast cancer risk. Women with a uterus were randomized to receive either estrogen plus progestin or a placebo. Progestin was added to protect women with a uterus from endometrial cancer. Women who have had a hysterectomy were randomized to receive either estrogen alone or a placebo. The estrogen plus progestin trial was stopped early on July 8, 2002 after an average follow-up of 5.2 years on the recommendation of the Data and Safety Monitoring Board. The estrogen alone study continued unchanged until March 2, 2004 when the NIH instructed participants to stop taking their study pills and to begin the follow-up phase of the study. . Participants in the estrogen alone study will be followed for eight to 12 years and have clinic visits every six months to assure safety and assess their health.

The dietary modification trial component studies the effect of a low-fat, high fruit, vegetable and grain diet on breast cancer, colorectal cancer and heart disease in 48,000 postmenopausal women. Participants are randomized to a comparison group which maintains usual dietary habits or to a dietary change group. Women in the dietary change group decrease their fat intake to 20 percent of total daily calories, increase fruit and vegetable consumption to five or more servings per day, and increase grains to six or more servings per day. Additionally, they monitor their food intake and attend nutrition group meetings to learn more about changing their diets in the first year. Thereafter they attend four meetings per year.

The calcium/vitamin D supplementation subtrial tests whether calcium and vitamin D supplements reduce the risk of hip and other fractures and colorectal cancer in postmenopausal women. Women in the hormone replacement therapy and the dietary modification trials are encouraged to join the calcium/vitamin D supplementation study. Approximately 45,000 postmenopausal women are randomized into one of two study groups. One group was randomly assigned to receive 1,000 mg of elemental calcium (as calcium carbonate) and 400 International Units of vitamin D₃daily. The second group received a matching placebo.

Women already taking calcium supplements can continue to take them. Participants will be followed for eight to 11 years and contacted by their clinical center every six months to assure their safety and assess their health.

Total number of trial participants in all three subtrials is 68,135.


The several goals of the study include: to give reliable estimates of extent to which known risk factors predict heart disease, cancers, and fractures; to identify new risk factors for these and other diseases in women; to compare risk factors, presence of disease at the start of the study and new occurrences of disease during the WHI in all study components; and to create a future resource to identify biological indicators of disease, especially substances and factors found in blood. The study enrolled 93,726 postmenopausal women and will track them for an average of nine years. Participants fill out periodic health forms and visit the clinic three years after enrollment. They take no medication and do not change their health habits.


The community prevention study consists of 12 separate studies conducted at eight of the Centers for Disease Control and Prevention's (CDC) University-based Prevention Research Centers through a cooperative agreement between NIH and CDC. The 12 studies began in October 1995 and continue for an additional five years. The collaboration supports health promotion and disease prevention research and demonstration projects that are community-based and focus on healthy behaviors that prevent the major causes of death and disability and that promote health practices that lead to more effective public health interventions. Each project provides research dissemination and translation of findings into community interventions. Topics under study include: attitudes towards hysterectomy, oophorectomy, and surgical menopause among African Americans; reducing cardiovascular disease risk among Black women; environmental and policy interventions to increase physical activity among minority women ages 40 to 75; peer support intervention for cardiovascular disease risk among African American women, aged 40 and older; assessing the effectiveness of a brief medical-provider educational intervention for osteoporosis in minority women aged 40 and older; improving the delivery of diabetes care to women in minority groups; and assessment of moderate physical activity among women.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Prevention
Actual Primary Completion Date : March 2005

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Postmenopausal women ages 50 to 79.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00000611

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Cancer Institute (NCI)
National Institute on Aging (NIA)
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OverallOfficial: Ross Prentice Fred Hutchinson Cancer Research Center

Additional Information:
Publications of Results:

Other Publications:
Women's Health Initiative Steering Committee: Effects of Conjugated Equine Estrogen in Postmenopausal Women Having Undergone Hysterectomy: The Women's Health Initiative Randomized, Controlled Trials. Obstet Gynecol Surv, 59(8):599-600, 2004.

Publications automatically indexed to this study by Identifier (NCT Number):
Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium, Swerdlow DI, Holmes MV, Kuchenbaecker KB, Engmann JE, Shah T, Sofat R, Guo Y, Chung C, Peasey A, Pfister R, Mooijaart SP, Ireland HA, Leusink M, Langenberg C, Li KW, Palmen J, Howard P, Cooper JA, Drenos F, Hardy J, Nalls MA, Li YR, Lowe G, Stewart M, Bielinski SJ, Peto J, Timpson NJ, Gallacher J, Dunlop M, Houlston R, Tomlinson I, Tzoulaki I, Luan J, Boer JM, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Ferrucci L, Bandenelli S, Tanaka T, Meschia JF, Singleton A, Navis G, Mateo Leach I, Bakker SJ, Gansevoort RT, Ford I, Epstein SE, Burnett MS, Devaney JM, Jukema JW, Westendorp RG, Jan de Borst G, van der Graaf Y, de Jong PA, Mailand-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Stephens JW, Eaton CB, Robinson JG, Manson JE, Fowkes FG, Frayling TM, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Redline S, Lange LA, Kumari M, Wareham NJ, Verschuren WM, Benjamin EJ, Whittaker JC, Hamsten A, Dudbridge F, Delaney JA, Wong A, Kuh D, Hardy R, Castillo BA, Connolly JJ, van der Harst P, Brunner EJ, Marmot MG, Wassel CL, Humphries SE, Talmud PJ, Kivimaki M, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Hakonarson H, Reiner AP, Keating BJ, Sattar N, Hingorani AD, Casas JP. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012 Mar 31;379(9822):1214-24. doi: 10.1016/S0140-6736(12)60110-X. Epub 2012 Mar 14.

Layout table for additonal information Identifier: NCT00000611     History of Changes
Other Study ID Numbers: 114
First Posted: October 28, 1999    Key Record Dates
Last Update Posted: April 15, 2016
Last Verified: January 2006
Additional relevant MeSH terms:
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Breast Neoplasms
Colonic Neoplasms
Bone Diseases
Heart Diseases
Coronary Disease
Myocardial Ischemia
Cardiovascular Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Metabolic Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Vascular Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Vitamin D