Women’s Health Initiative study

CD Since the publication of the Women s Health Initiative study, there has been an increase in the use of non-hormonal therapies for the management of menopausal symptoms. Particularly for women with CHD and breast cancer risk factors, non-hormonal therapies may offer an alternative to assist with symptom management. A wide range of therapies, both prescription and herbal, have been studied with varying degrees of success. In choosing a particular therapy, it is important to match patient symptoms with a therapy that is not only effective but also safe. 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

Many studies have evaluated the relationship between exogenous hormones and development of breast cancer. Postmenopausal estrogen replacement therapy has been the subject of several recent meta-analyses, with conflicting results. The recently reported NCI-sponsored Women s Health Initiative study randomized 80,000 women to take postmenopausal estrogen replacement therapy combined with progesterone or a placebo. This study reported an... 

The Women s Health Initiative Study Group (1998) Design of the Women s Health Initiative clinical trial and... 

Calleja-Agius J, Brincat MP. Hormone replacement therapy post Women s Health Initiative study where do we stand Curr Opin Obstet Gynecol 2008 20 513-8. 

As of 1995, almost 38% of all women 50 to 75 years of age were using HRT.1 It was in 1996 that the United States Preventive Services Task Force (USPSTF) first published its recommendations that not all postmenopausal women should be prescribed HRT, but rather, therapy should be individualized based on risk factors. This recommendation was further supported with publication of the Heart and Estrogen/Progestin Replacement Study (HERS) in 1998, which demonstrated that women who had established CHD were at an increased risk of experiencing a myocardial infarction within the first year of HRT use compared with a similar group of women without CHD risk factors. As a result, the authors concluded that HRT is not recommended for the secondary prevention of CHD.2 Then, in 2002, the Women s Health Initiative (WHI) report was published. This trial demonstrated that HRT was not protective against CHD but... 

WHIMS Women s Health Initiative Memory Study... 

Espeland MA, Rapp SR, Shumaker SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women Women s Health Initiative memory study. JAMA 2004 291 2959-2968. 

Mares, J. A., T. L. LaRowe et al. (2006). Predictors of optical density of lutein and zeaxanthin in retinas of older women in the carotenoids in age-related eye disease study, an ancillary study of the women s health initiative. Am. J. Clin. Nutr. 84(5) 1107-1122. 

LaRowe, TL, Mares, JA, Snodderly, DM, Klein, ML, Wooten, BR, and Chappell, R, 2008. Macular pigment density and age-related maculopathy in the Carotenoids in Age-Related Eye Disease Study. An ancillary study of the women s health initiative. Ophthalmology 115, 876-883 e871. 

Moeller, SM, Parekh, N, Tinker, L, Ritenbaugh, C, Blodi, B, Wallace, RB, and Mares, JA, 2006. Associations between intermediate age-related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age-related Eye Disease Study (CAREDS) Ancillary study of the Women s Health Initiative. Arch... 

The continuous combined oral estrogen-progestogen arm of the Women s Health Initiative (WHI) study was terminated prematurely after a mean of 5.2-year follow-up because of the occurrence of a prespecified level of invasive breast cancer. The study also found increased coronary disease events, stroke, and pulmonary embolism. Beneficial effects included decreases in hip fracture and colorectal cancer. 

Finally, a major question in SERM development is whether the new compounds will behave like estrogens with respect to cardiovascular events, which would be a worthless property given the results of the WHI trial (Writing Group for the Women s Health Initiative Investigators 2002 Women s Health Initiative Steering Committee 2004). This is a complex issue that will depend on the unique profile of action of the new SERM on the different components of the atherosclerosis process and the patient population and study design and conduct that is implemented. 

Shumaker SA, Legault C, Kuller L, Rapp SR, Thai L, Lane DS, et al. (2004) Conjugated equibe estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women. Women s Health Initiative Memory Study. J Am Med Assoc 291 2947-2958... 

Estrogens with or without progestins should not be used for the prevention of cardiovascular disease. The Women s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 19 years of age) during 5 years of treatment with oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo.62... 

A study that cannot be faulted on that score is the Women s Health Initiative, a randomized, controlled, primary prevention trial (planned to last for 8.5 years), in which 16 608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited at 40 US clinical centers over the period 1993-98 (9). In one part of this study, 8506 participants received conjugated equine estrogens 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day 8102 were given placebo. The primary desired outcome was reduction of coronary heart disease (non-fatal myocardial infarction and death), with invasive... 

Other published studies, many of which are of limited scope, do not run closely parallel to the above findings from the Women s Health Initiative, and the data on cardiovascular effects remain particularly confusing. However, Beral and colleagues have pointed out optimistically that substantial new data should soon be available from randomized trials of estrogen-alone hormonal replacement therapy versus placebo, although they added that few additional trial data on combined hormone replacement therapy are expected for about a decade (10). They also pointed out that existing randomized trials are too small to provide reliable evidence on some basic matters, including the relative risks of the various compounds in use. 

In the Women s Health Initiative Calcium/Vitamin D Trial, a large number of postmenopausal women (n = 36,282) were supplemented with 1000 mg of elemental calcium and 400 IU vitamin D daily or placebo for 7 years. The study found no significant decrease in either systolic or diastolic blood pressure (Margolis et al., 2008). The results from the Women s Health Initiative Trial further emphasized the importance of dairy per se rather than calcium for the effect on blood pressure. 

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