Effects of Estrogen-Alone on Dementia and Cognitive Function - Findings from the Women's Health Initiative Memory Study (WHIMS)

June 2004

Findings Summary

The purpose of the Hormone Program in the Women’s Health Initiative is to study the health benefits and risks of hormone therapy for postmenopausal women. In March 2004, women in the Estrogen-Alone (CEE) Study were asked to stop taking their study pills because no overall benefit was found during 6.8 years of follow-up. WHI researchers concluded that CEE should not be used to prevent chronic disease overall.
Another important question being asked about hormones and women’s health is how CEE affects women’s thinking, or cognition, including:
  • Normal cognitive function (thinking abilities like memory, attention, concentration, language, abstract reasoning, and calculation)
  • Mild cognitive impairment (a significant decline or drop in at least one cognitive ability)
  • Dementia (a significant drop in several cognitive abilities, not related to other medical problems, but clearly interfering with day-to-day activities)
The WHI Memory Study (WHIMS) is a sub-study within the WHI Hormone Program, designed to address these issues using scientific testing of women’s cognitive function over time. The data from the CEE part of WHIMS have now been analyzed and appear in the June 23, 2004 issue of the Journal of the American Medical Association.
WHIMS studied both normal cognitive function and abnormal cognitive decline (mild cognitive impairment and dementia). As described in these two papers, 2,947 CEE participants between the ages of 65 and 79 years agreed to participate in WHIMS and completed an assessment once a year to study their cognitive function. Some women also had more detailed testing, including meeting with a specialist who evaluated whether their cognitive function had declined abnormally and whether mild cognitive impairment or dementia was present.
The results from the CEE part of WHIMS showed that estrogen alone does not protect women from normal declines in cognitive function when compared with placebo. Women taking the hormone tested slightly worse over time on the yearly cognitive function questions, although the differences were small and would probably not be noticeable to anyone. The greatest cognitive decline was seen in women who had lower cognitive function when WHIMS began.
76 women in the CEE group developed mild cognitive impairment compared to 58 women in the placebo group. This finding indicates that estrogen alone does not protect postmenopausal women from the milder type of abnormal cognitive decline. CEE use increases the risk of developing mild cognitive impairment.
Women taking CEE also appeared to be at somewhat higher risk for developing dementia than those taking placebo. 47 women in WHIMS were found to have probable dementia -- 28 were taking CEE and 19 were taking placebo pills. An analysis of both CEE and CEE plus MPA (Estrogen plus Progestin) together showed that more women taking active hormones developed either dementia or mild cognitive impairment.
These results from WHIMS apply only to women 65 and older who took CEE. It is unknown if these findings apply to women under age 65.
Women in the CEE study were randomized to daily take either a placebo (inactive) pill or an active pill containing 0.625 mg of conjugated equine estrogens (CEE, commonly known as Premarin®). The CEE was taken alone, without the addition of a progestin. CEE participants had a hysterectomy before joining the WHI, so they did not need to worry about estrogen effects on endometrial (uterine) cancer.
Further follow-up of the WHIMS participants is planned to determine whether the increased risk for dementia and mild cognitive impairment continues after treatment is discontinued.