Characteristics of WHIMS and CoSTAR women at the time of enrollment into their parent WHI and STAR trials were balanced with respect to treatment assignment within each trial (). However, differences between trial cohorts with respect to many of the characteristics are evident. Compared with WHIMS women, CoSTAR women tended to be younger and were less likely to have a college education, less likely to be from an ethnic minority, less likely to have diabetes, and more likely to have had a hysterectomy. The distributions of obesity and the prevalences of hypertension were similar between the two trials. The baseline mean 3MS (SD) scores of the four treatment groups also appear in . These did not differ significantly between trials, and their cumulative distributions were nearly identical ().
Characteristics of WHIMS and CoSTAR Women at Enrollment into WHI and STAR Trials: Grouped According to Treatment Assignment
Cumulative distribution of baseline 3MS scores from the WHIMS and CoSTAR cohorts.
At baseline, age-adjusted associations of 3MS scores with education, BMI, hypertension, and diabetes status appeared to be fairly similar in the two study cohorts (nonsignificant tests of interactions) (). Relationships that 3MS scores had with hysterectomy status differed between trials (p
0.046), so that results of analyses stratified by hysterectomy status are presented. Because of small cell sizes, there was little power to detect between-trial differences in relationships that 3MS scores had with ethnicity, for which the trial's distributions differed markedly. Because of this, we focused this report on analyses limited to Caucasian participants (87% of WHIMS women; 91% of CoSTAR women), whose baseline mean 3MS scores are shown in . We also conducted analyses using the full cohort with covariate adjustment for the most prevalent ethnic groups; these yielded comparable results and are not reported.
Age-adjusted Relationships Between Baseline Dementia Risk Factors and 3MS Scores in WHIMS and CoSTAR
Most women in this CoSTAR cohort had only 2 or fewer years of follow-up (). Follow-up rates did not vary by treatment assignment. Among these WHIMS women, follow-up of ≤2 years was more common among women who were older or less educated or had diabetes (all p
0.05). Because of the earlier termination of the CEE
MPA trial, follow-up was shorter for women without prior hysterectomy. In this CoSTAR cohort, none of these relationships approached statistical significance. provides fitted mean 3MS scores (from the log-transformed data), with adjustment for baseline 3MS, age, education, BMI, hypertension, and diabetes status. These estimates were from Caucasian participants and stratified by hysterectomy status. The log-transformation, by reducing the skew, yielded means that were greater than raw averages. Adjusted 3MS means were slightly lower among women assigned to active therapies compared with the WHIMS placebo at most time points. When averaged across follow-up, these did not reach statistical significance for women without prior hysterectomy (overall, p
0.18): 97.56 (95% CI 97.49-97.63, placebo), 97.48 (97.40-97.55, (hormone therapy), 97.32 (96.78-97.80, raloxifene), and 97.16 (96.56-97.69, tamoxifen). For women with prior hysterectomy, differences among arms were ordered similarly and reached statistical significance (p
0.007). Pairwise (unadjusted for multiple comparisons) p
values contrasting active therapies with placebo were p
0.10 (hormone therapy), p
0.09 (raloxifene), and p
0.003 (tamoxifen). The adjusted means were 97.29 (97.19-97.38, placebo), 97.17 (97.06-97.27 hormone therapy), 96.89 (96.41-97.34, raloxifene), and 96.55 (96.02-97.04, tamoxifen). portrays these differences as mean deficits from the perfect score of 100.
Table 3. Fitted Mean 3MS Scores, by Treatment Assignment, with Adjustment for Age, Education, Diabetes, Hypertension, BMI, and Baseline 3MS (Whites Only): Stratified by Hysterectomy Status and Based on Log Transformation of (102 - 3MS Score): Included in Each (more ...)
FIG. 2. Mean deficits from 100 adjusted postrandomization 3MS scores across years 1–3 of follow-up. Estimates were limited to white participants and included age, baseline 3MS score, education, BMI, hypertension, and diabetes as covariates. Means are (more ...)
Because patterns appeared similar, an analysis was conducted that included women both with and without a uterus (with hysterectomy status as a covariate). Treatment groups means were 97.46 (97.40-97.52, placebo), 97.36 (97.30-97.42, hormone therapy), 97.14 (96.79-97.47, raloxifene), and 96.88 (96.49-97.24, tamoxifen). With the larger sample size, overall differences were statistically more marked (p
0.001). Differences from placebo were most striking for tamoxifen (p
0.001) and less so for hormone therapy (p
0.02) and raloxifene (p
Mean adjusted 3MS scores over follow-up were also estimated for the subset of Caucasian women with baseline 3MS score <95, 1746 (28.1%) of the WHIMS participants and 86 (31.4%) of the CoSTAR participants. Because of the limited sample size, analyses were pooled across hysterectomy status, which was included as an additional covariate. The adjusted mean postrandomization 3MS scores for women were 95.51 (95.33-95.68, placebo), 95.25 (95.07-95.43, hormone therapy), 94.46 (93.41-95.38, raloxifene), and 94.15 (93.04-95.12, tamoxifen). Overall differences among groups were significant (p
0.003), with the most marked differences between placebo and each of the active therapies. portrays the mean differences between each therapy and placebo for the women with baseline 3MS scores <95 and, for comparison, for all women. For each therapy, the relative decrements appeared to be larger for women with lower baseline 3MS scores: 0.26 (SE
0.004) vs. 0.09 (0.001) for CEE therapy, 1.05 (0.41) vs. 0.32 (0.14) for raloxifene, and 1.36 (0.44) vs. 0.58 (0.16) for tamoxifen. For the separate tests of interaction between baseline 3MS and the relative effects of each drug vs. placebo, the p
values were p
0.03 (CEE), p
0.08 (raloxifene), and p
Estimated mean relative decrements in postrandomization 3MS scores of active therapies compared with placebo therapy. Estimates are provided for all women and for the subset of women whose baseline 3MS score was <95.