What We Think and What We Know

This is an editorial that has found a voice only after a lot of struggle about what ought to be said and what ought not. In this issue, Crespo et al. (1) examined data from the Third National Health and Nutrition Examination Survey (NHANES III) and reported that postmenopausal women taking hormone replacement therapy (HRT) have better lipoprotein profiles as well as some improvement in components of the metabolic syndrome when compared with those not taking HRT.

Timing is everything. When the authors prepared the manuscript, when the reviewers and editors accepted it, and in fact when we were asked to prepare this editorial, studies like these were sufficient reason for health care providers to recommend that their postmenopausal diabetic patients consider HRT. In the absence of randomized controlled clinical-trial data, cross-sectional data suggesting benefits for intermediate measures of cardiovascular disease (CVD) risk might constitute “best evidence.” In the HRT field, epidemiological studies inconsistently demonstrating an increased risk of breast cancer were the major limitation to wholesale adoption of HRT in our society.

Diabetic women suffer from four times the risk of CVD as nondiabetic women. Until a few weeks ago, the prevailing wisdom, based on such cross-sectional data, was to prescribe HRT for postmenopausal woman, with an aim to reduce CVD risk, prevent osteoporosis, and with exuberant hope, preserve memory, thwart dementia, keep skin supple, promote sexual well-being, as well as promote overall health and vitality. Many astute physicians were vexed by the results of the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized controlled study published in 1998 that demonstrated that HRT had an early adverse effect in women with preexisting coronary disease (2). The authors suggested “given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this …