Women's Health Initiative (WHI)
Condition: Bone Diseases; Breast Neoplasms; Cardiovascular Diseases; Colonic Neoplasms; Coronary Disease; Heart Diseases; Myocardial Ischemia; Osteoporosis; Postmenopause
MeSH terms: Neoplasms; Breast Neoplasms; Colonic Neoplasms; Osteoporosis; Bone Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia
Study type: Interventional
Phase: Phase 3

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).
    

Detailed description: 
      BACKGROUND:

      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).

      DESIGN NARRATIVE:

      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.

      CLINICAL TRIAL COMPONENT

      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.

      OBSERVATIONAL STUDY

      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.

      COMMUNITY PREVENTION STUDY

      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.
    

Intervention name(s): hormone replacement therapy; estrogens; progestins; estrogen replacement therapy; diet, fat-restricted; calcium; vitamin D; dietary supplements
Intervention type(s): Drug; Drug; Drug; Drug; Behavioral; Drug; Drug; Behavioral
Intervention MeSH terms: Vitamin D; Calcium; Hormones; Estrogens; Progestins
Allocation: Randomized
Primary purpose: Prevention