Memory Study and Hormone Therapy

On August 10, 2010, in Health Articles, by admin

Once again, we are confronted with disturbing headlines admonishing women that hormone therapy (HT) should not be used for the prevention and treatment of chronic disease. In fact, new reports have suggested that HT may accelerate the decline in cognitive function and double a woman’s risk of Alzheimer’s disease (AD). Do the results of the Women’s Health Initiative Memory Study (WHIMS) reported by Shumaker and Rapp repudiate decades of basic science, clinical observational studies, and clinical trials that lead us to believe use of HT would slow age-related cognitive decline and significantly reduce a woman’s risk of AD? What are the implications for women considering initiation of HT and for those currently on HT?

At the time that the WHIMS trial began as an ancillary study to the two larger Women’s Health Initiative (WHI) HT trials, observational studies revealed that women with a history of HT use at any time had a reduced risk of AD. These data were supported by some, but not all, observational studies and intervention trials demonstrating that HT exposure was associated with better cognitive function. An extensive body of knowledge developed by neurobiologists in experimental animal models has demonstrated multiple beneficial effects of estrogen on neuronal structure and function, providing a compelling scientific rationale that estrogen therapy would have a beneficial effect on cognitive function and brain aging. The Women’s Health Initiative (WHI) study provided a unique opportunity to determine the effect of HT on brain aging and AD. Of the 27,000 women participating in the HT component of WHI, WHIMS recruited 7,480 non-demented women; 4,532 were randomized to either combination HT (0.625 mg conjugated equine estrogen (CEE) plus 2.5 mg of medroxyprogesterone acetate) or placebo daily. The remaining 2,948 women who had undergone a hysterectomy were randomized to an unopposed estrogen arm, 0.625 mg of CEE, of the WHI. Because the primary outcome was the incidence of AD and dementia, recruitment was limited to women over age 65 years in order to achieve sufficient events to detect an effect of HT. Thus, the mean age of the population was slightly over age 70 years when HT was initiated.

The principal finding of the first of the two reports from WHIMS was an increased incidence of dementia in women on HT (45 vs 22 events per 10,000 person-years) resulting in a hazard ratio of 2.05 (95% CI 1.21 – 3.48). Although this outcome would not have been anticipated 10 years ago, it is very consistent with the results obtained from the Cache County Study published in JAMA last year .

In that prospective observational study, men and women with an average age of 73 years were assessed at two points at an interval of 3 years for incident dementia. Ascertainment of AD and other dementias used a similar tiered screening process as in WHIMS. Both studies used a pre-determined cut-point on the modified Mini-Mental State Examination (3MSE) to identify participants for additional testing and ultimate evaluation by a physician and laboratory studies. What was unique about the Cache County Study is that past and current users of HT were analyzed separately. The average age of patients currently using HT for less than 10 years was 70 years, and therefore had initiated HT after the age of 60 years. The point estimate for the hazard ratio of incident AD was 2.41 in women who currently used HT for <3 years, and 2.12 in women using HT for 3 to 10 years, remarkably similar to the point estimate of risk of 2.05 observed in WHIMS. On the other hand, past users of HT for <3 years had a 42% reduction in incident dementia, whereas past users of HT for >10 years experienced an 83% reduction in incident dementia.

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