PI: Charles L. Kooperberg, Ph.D., Fred Hutchinson Cancer Research Center, Seattle
The Women's Health Initiative (WHI) is a long-term national health study that has focused on strategies for preventing heart disease, breast and colorectal cancer and osteoporotic fractures in postmenopausal women. These chronic diseases are the major causes of death, disability and frailty in older women of all races and socioeconomic backgrounds.
This cohort is sponsored by the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), involves 161,808 women aged 50-79, and is one of the most definitive, far-reaching clinical trials of post-menopausal women's health ever undertaken in the U.S. Women were recruited between 1993 to 1998 at 40 centers across the US and follow up is planned to continue until at least 2015. The WHI Clinical Trial and Observational Study focused on many of the inequities in women's health research and will continue to provide practical information to women and their physicians about hormone therapy, dietary patterns, calcium/vitamin D supplementation, and their effects on the prevention of heart disease, cancer and osteoporotic fractures.
The WHI has two major parts: a randomized Clinical Trial and an Observational Study. The randomized controlled Clinical Trial (CT) enrolled 68,132 postmenopausal women between the ages of 50-79 into trials testing three prevention strategies. If eligible, women could choose to enroll in one, two, or all three of the trial components. The components are:
* Hormone Therapy Trials (HT): This component examined the effects of combined hormones or estrogen alone on the prevention of coronary heart disease and osteoporotic fractures, and associated risk for breast cancer. Women participating in this component took hormone pills or a placebo (inactive pill) until the Estrogen plus Progestin and Estrogen Alone trials were stopped early in July 2002 and March 2004, respectively. All HT participants continued to be followed without intervention until close-out.
* Dietary Modification Trial (DM): The Dietary Modification component evaluated the effect of a low-fat and high fruit, vegetable and grain diet on the prevention of breast and colorectal cancers and coronary heart disease. Study participants followed either their usual eating pattern or a low-fat dietary pattern.
* Calcium/Vitamin D Trial (CaD): This component began 1 to 2 years after a woman joined one or both of the other clinical trial components. It evaluated the effect of calcium and vitamin D supplementation on the prevention of osteoporotic fractures and colorectal cancer. Women in this component took calcium and vitamin D pills or a placebo.
The Observational Study (OS) is examining the relationship between lifestyle, health and risk factors and specific disease outcomes. This component involves tracking the medical history and health habits of 93,676 women.
To fully examine the profile of gene and environment interaction, or "epidemiologic architecture," we will comprehensively evaluate such putative genuine variants in the Women's Health Initiative This large study population not only enables us to examine the population incidence for racial and ethnic subgroups and associated risks of rigorously defined, incident diseases (specific aim 1) but allows us to investigate associated risks given in-depth information on various environmental exposures and disease risk factors as well as three randomized interventions (hormone therapy; low-fat dietary modification; calcium + vitamin D supplements) (specific aim 2). The prospective and longitudinal collection of biospecimens, intermediate outcomes, and phenotypic characteristics, such as bone mineral density, hormone concentrations, breast density, or inflammation will further permit us to link genetic variants to relevant intermediate phenotypes, which will potentially provide important clues to the biological basis of the genuine associations (specific aim 3). For a variety of outcomes we will genotype within this 4-year project 72,000 participants for disease-specific putative genuine variants. Information generated from this study will be critical to determine the health impact of any given undisputable variant. Findings may also provide valuable insights into disease pathways and mechanisms, and targets for disease screening, prevention, and treatment.