The Women's Health Initiative: A Landmark Resource for Skeletal Research Since 1992

Abstract

The Women's Health Initiative (WHI) is a large longitudinal study designed to investigate strategies for the prevention and control of common chronic diseases in postmenopausal women, including cardiovascular disease, cancer, and osteoporotic fractures. The WHI consisted of three overlapping clinical trials of hormone therapy, diet modification to reduce total dietary fat, and calcium/vitamin D supplementation. Women who were ineligible for the hormone therapy or diet modification trials or not interested were invited to participate in the observational study. Women were recruited into WHI from 1993 to 1998 at 40 US clinical centers. WHI enrolled 26,046 underrepresented minority women and 135,762 white women. Women could participate in each trial if eligible. The final enrollment included 27,347 women in the hormone trial; 48,835 women in the diet modification trial; 36,282 women in the calcium/vitamin D trial, and 93,676 in the observational study. After the main study ended in 2005, women were invited to continue follow-up for exposures and outcomes through two extensions to 2020. Proposals were recently submitted to continue follow-up through 2027. Information was collected on an extensive number of risk factors for fractures at baseline and over the follow-up, including fall and fracture history, weight patterns, comorbidities, diet, reproductive history, medications, anthropometry, and biomarkers. Bone mineral density was measured at three WHI clinical centers (n = 11,020) chosen to maximize race/ethnic diversity. WHI encourages outside investigators to make use of the publicly available WHI data and to access the biobank of specimens (www.whi.org).

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

“…Recruitment included mailings to 71,521 active Women's Health Initiative (WHI) Extension Study participants ( 37 ) and mailings by Brigham and Women's Hospital (BWH) to 237,736 women and men contacted for, but not randomly assigned to, the VITamin D and OmegA-3 TriaL (VITAL) ( 38 ); mass mailings to 2,616,343 US men and women; and mailings to 3380 volunteers through other sources, including responses to media stories and advertisements. Of 191,796 participants completing a brief screening questionnaire, 120,629 were initially eligible and willing; then 63,025 completed another questionnaire with written informed consent before enrollment with oversight by the Human Subjects Committee at BWH.…”

Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

“…Briefly, an embedded recruitment approach was conducted from June 2015 to March 2018 with mailings to active participants in the Women's Health Initiative (WHI) Extension Study ( 33 ), mailings by Brigham and Women's Hospital (BWH) to women and men contacted for but not randomly assigned to the VITamin D and OmegA-3 TriaL (VITAL) ( 34 ), mass mailings, and mailings to volunteers who heard about the study through various sources ( Supplementary Methods ). To be eligible, participants agreed to forego personal MVM and cocoa extract supplement use during the trial, limit vitamin D to ≤1000 IU/d and calcium to ≤1200 mg/d from all supplemental sources, and complete at least a 2-mo placebo run-in phase taking ≥75% of the study pills.…”

Pregnancy loss and risk of incident CVD within 5 years: Findings from the Women's Health Initiative

“…Briefly, WHI is a large-scale prospective study of postmenopausal women, aged 50–79 at baseline, who were enrolled at 40 clinical centers throughout the United States between 1993 and 1998. The main WHI study concluded in 2005; follow-up of surviving participants is ongoing in WHI Extension Studies ( 16 ). The WHI study involves both an observational study (OS) arm and three overlapping randomized trials.…”