Review in Brief
Effects of estrogen plus progestin on cognitive functioning and the risk of developing dementia: Findings from the WHI Memory Study
The purpose of the Women's Health Initiative hormone program is to study the health benefits and risks of hormones for postmenopausal women. In July 2002, women in the estrogen plus progestin part of the hormone program were asked to stop taking their study pills because these women had a higher risk of breast cancer than those taking placebo pills. Furthermore, the overall risks - including heart attacks, stroke, blood clots, and breast cancers - outweighed the benefits of fewer fractures and colorectal cancers.
An important question being asked in the WHI hormone program is whether taking estrogen alone or estrogen plus progestin lowers the risk both of normal declines in cognitive functions (memory and other 'thinking' abilities), and of abnormal declines known as 'mild cognitive impairment' (a significant drop in at least one cognitive ability) and 'dementia' (a significant drop in several cognitive abilities that markedly interferes with daily functioning and is not due to other medical conditions). The WHI Memory Study (WHIMS) is a sub-study within the WHI hormone program that is carefully designed to answer these questions. The data from the estrogen plus progestin part of WHIMS have now been analyzed and appeared in the May 28, 2003 issue of the Journal of the American Medical Association. The estrogen-alone part of the WHI hormone program and the WHIMS sub-study continue, and results will be available when this study is completed.
Over 4500 women between the ages of 65 and 79 years who are participating in the WHI estrogen plus progestin hormone program also agreed to participate in WHIMS. For an average of 4 years, half of the women received a daily hormone pill (0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate, known as PremPro™ by Wyeth), and the other half received a placebo (inactive) pill. Women participating in WHIMS were asked to stop taking the estrogen plus progestin in July 2002, at the same time as the other participants in the WHI hormone program.
As part of WHIMS, women are asked questions once a year testing their memory and other cognitive functions (attention, concentration, language, abstract reasoning and calculation). Some women also undergo a more detailed set of cognitive tests, and are evaluated by a specialist in cognitive functioning. The purpose of this evaluation process is to determine whether the participants' cognitive function had declined abnormally, and whether mild cognitive impairment or dementia is present. Thus, WHIMS is examining both normal cognitive decline and abnormal cognitive decline (mild cognitive impairment, dementia).
The results from the WHIMS estrogen plus progestin trial showed that the combination hormone therapy does not protect women from normal cognitive decline when compared with the placebo. Women taking the hormone combination performed slightly worse on the yearly test, though the differences were small and would probably not be noticeable to anyone. Concerning the risk of developing dementia, women taking estrogen plus progestin were actually at higher risk than women taking placebo. That is, women taking estrogen plus progestin were twice as likely to develop dementia over the course of the study. While this difference is important and clearly indicates that estrogen plus progestin increases the risk of developing dementia in postmenopausal women, the actual number of cases of dementia was small. Overall, 61 women were found to have probable dementia. Forty of these women were taking estrogen plus progestin and 21 were taking the placebo pill. This translates into 23 more cases of dementia per year for every 10,000 women 65 and older taking the combination hormone therapy. With regard to the less severe cognitive decline, women in the estrogen plus progestin group developed mild cognitive impairment at the same rate as women in the placebo group (estrogen plus progestin=56 cases per 10,000 women every year; placebo=55 cases per 10,000 women every year), indicating that this hormone combination does not protect postmenopausal women from milder cognitive decline.
These results apply only to women 65 and older who take estrogen plus progestin. They do not apply to women who are taking estrogen alone. This part of the WHI Memory Study hormone study is continuing, and the results are not yet known. Furthermore, women in the estrogen plus progestin part of WHIMS continue to be followed, even though they have been asked to discontinue taking the hormone combination. Scientists hope to continue to study the effects of terminating combination therapy on cognitive function.