Women's Health Initiative
[2][3] In the years following the WHI, studies have shown a decrease in breast cancer rates in postmenopausal women, attributed to the decline in use of hormone replacement therapy.
[6] In the 1980s, it had become apparent that past biomedical research had focused disproportionately on white men, often neglecting prevention and treatment studies of diseases that are either unique to or more common in women and minorities.
[citation needed] In 1990, however, a report was published by the General Accounting Office (GAO), at the request of the Congressional Caucus on Women's Issues, which stated that this NIH policy was not being adequately applied to research grant applications.
[7] It was these changes in societal attitudes and policy toward women's health research, in addition to the demonstration that such a large study was not only feasible, but could be done economically, that gave rise to the WHI.
[citation needed] Among postmenopausal women, cardiovascular disease, cancer, and osteoporosis are the leading causes of morbidity and mortality, as well as impaired quality of life.
[citation needed] It had been generally accepted that postmenopausal estrogen deficiency may play a role in these morbidities, and that dietary, behavioral, and drug interventions may forestall their development.
Such interventions would require testing through clinical trials before they, along with their full range of risks and benefits, could be used as the basis for setting public health policy and creating prevention guidelines.
[citation needed] However, concerns existed about the feasibility of such a complex clinical trial among participants in this demographic of older women, particularly with respect to sufficient recruitment and adherence to the dietary and hormone-treatment regimens.
[citation needed] In 1984, the NIH provided funding for a feasibility study pertaining to diet adherence, conducted by the Women's Health Trial (WHT).
The WHT, which commenced in 1986 and involved 303 women randomized into dietary intervention and control groups, yielded results demonstrating a high degree of adherence on the basis of both food-intake questionnaires and clinical laboratory findings.
[13][14] The WHT did not proceed with its full-scale trial, as it was not awarded further funding from the NIH on the basis of the potential inability of the study to test the hypothesis in a larger cohort of women.
[citation needed] On April 19, 1991, Dr. Bernadine Healy, newly appointed as the first female director of the NIH, announced her plan for the Women's Health Initiative (WHI).
To this end, the WHI maintained a carefully designed organizational structure, along with governance- and science-specific committees and communications channels for staff and investigators to resolve study-related questions and exchange information.
The wide nature of the age range balanced the need to observe the effects of hormone therapy on younger women, while also attempting to capture physical and cognitive outcomes in older populations.
[citation needed] For the CT, a partial factorial study design was utilized for the investigation of three overlapping interventions (dietary modification, hormone therapy, and calcium/vitamin D supplementation), as this would provide considerable cost efficiencies.
As such, the primary outcome of interest was coronary heart disease, as this is a major cause of morbidity and mortality among women, particularly those over age 65, and because, at the time, no clinical trial had been undertaken to prove the cardioprotective effects of HT.
The addition of progestin has been linked to a marked reduction in the risk for the development of endometrial cancer in women receiving estrogen treatment who have not undergone a hysterectomy.
[1][54][55][56][57] Large reductions in HT prescriptions ensued,[58][59][60][61] resulting in a substantial loss of revenue in sales of this class of drugs, with a presumably commensurate savings to patients and insurers.
[63] When they first evaluated the impact of HRT in 1996, the USPSTF assigned a "B" grade to hormone replacement therapy for use in primary prevention of chronic conditions in postmenopausal women, basing their results on observational studies and short-term trials.
[74] The calcium/vitamin D (CaD) trial component was designed to test the hypothesis that women taking a combination of calcium and vitamin D will experience a reduced risk of hip and other fractures, as well as breast and colorectal cancer.
[citation needed] Women participating in this intervention were randomly assigned to receive a regimen of 1000 mg calcium in combination with 400 International Units (IU) of vitamin D (n = 18176) or a placebo (n = 18106), and were followed for an average of 7 years, with monitoring for bone density, fractures, and pathologically confirmed cancers as the measures of outcomes.
However, subgroup analysis revealed a possible benefit to older women in terms of a reduced risk of hip fractures, attributable to calcium plus vitamin D supplementation.
In-person visits were conducted to assess and collect physical and functional measurements, as well as blood to replenish the WHI biospecimen repository and determine current CBC parameters for these participants.
The study has enrolled nearly 50,000 participants as of October 2016,[103] whose assigned interventions will include varying physical activity routines, which are monitored by mail and via phone, using an interactive voice response (IVR) system.
[104] Analysis during the post-intervention period following the estrogen-plus-progestin trial continues to reveal the strong association between estrogen- plus-progestin usage and breast cancer risk.
The most recent update, published July 28, 2020 in JAMA,[105] reported that increased breast cancer risk has persisted among women randomized to estrogen plus progestin compared with placebo (hazard ratio [HR], 1.28; 95%CI, 1.13 -1.45; P-value < 0.001).
According to a cumulative 18-year follow-up analysis published in 2017, it was found that, among 27,347 postmenopausal women who had originally participated in the WHI hormone therapy trials, interventions using estrogen-plus-progestin and estrogen-alone were not associated with increased or decreased risk of all-cause, cardiovascular, or total cancer mortality.
Post-menopausal women considering initiation of HT and their clinicians should refer to previous WHI publications for a complete summary of risks for fatal and non-fatal events.
After a median 16.1 years of cumulative follow-up (inclusive of the intervention period), further analysis showed that this benefit persisted (234 deaths versus 443 in the "normal diet" arm; HR, 0.82; 95% CI, 0.70 to 0.96 with P = .01).
[130] Study has collected wide-ranging data and has focused on risk factors that predict vascular disease, diabetes, cognitive impairment and dementia — and the benefits of living a healthy lifestyle.[131](1979–present).
