No Cognitive Benefit from Estrogen in Younger Postmenopausal Women

The use of conjugated equine estrogens (CEEs) in postmenopausal women aged 50 to 55 years was not associated with any long-term benefit or risk to cognitive function, according to findings of the Women’s Health Initiative Memory Study of Younger Women (WHIMSY), an extension of the Women’s Health Initiative Memory Study.¹
   
CEEs are the most commonly used postmenopausal hormone therapy in the United States, and their use in older postmenopausal women has been associated with adversely affecting cognitive function. The purpose of this study was to determine whether the use of CEEs in younger postmenopausal women-those aged 50 to 55 years-was associated with similar negative effects on cognitive function.

Postmenopausal women aged 50 to 55 years who began treatment with CEE (0.625 mg) with or without medroxyprogesterone acetate (2.5 mg) or placebo were included in the study. Treatment continued for an average of 7 years. A total of 1326 women were enrolled in WHIMSY; of those, 1168 participated in phone interviews conducted about 7 years after the trial ended to assess cognitive function. The mean age of participants at the time of the interviews was 67.2 years.
   
The study authors found no differences in global cognitive function scores-the primary outcome-between study groups. In addition, the scores for secondary outcomes, such as verbal memory, attention, executive function, verbal fluency, and working memory, were similar between study groups. These findings applied to women regardless of whether synthetic progestin was part of their regimen.
   
The study authors found some evidence that therapy with CEEs may adversely affect verbal fluency in women with a history of hysterectomy or previous use of hormone therapy (mean treatment effect, -0.17 and -0.25, respectively), but they acknowledge that this finding may be the result of chance.
   
“In contrast to findings in older postmenopausal women, this study tells us that taking these types of estrogen-based hormone therapies for a relatively short period of time in their early postmenopausal years may not put them at increased risk for cognitive decline over the long term,” said Susan Resnick, PhD, chief of the National Institute on Aging’s Laboratory of Behavioral Neuroscience and study coauthor.² She continues, “Further, it is important to note that we did not find any cognitive benefit after long-term follow-up.”

Pertinent Points:
- No meaningful differences were found in the average global cognitive function scores between postmenopausal women administered conjugated equine estrogen (CEE) and those administered placebo.
- It is unknown whether initiating CEE-based therapy during menopause and continuing treatment until symptoms have passed has any short- or long-term affect on cognitive function.

References
1. Espeland MA, Shumaker SA, Leng I, et al. for the WHIMSY study group. JAMA Intern Med. June 24, 2013:1-8. doi: 10.1001/jamainternmed.2013.7727. [Epub ahead of print]
2. National Institutes of Health. Estrogen therapy has no long-term effect on cognition in younger postmenopausal women [press release]. Available at: http://www.nih.gov/news/health/jun2013/nia-24.htm. Accessed July 12, 2013.
 

References:

1. Espeland MA, Shumaker SA, Leng I, et al. for the WHIMSY study group. JAMA Intern Med. June 24, 2013:1-8. doi: 10.1001/jamainternmed.2013.7727. [Epub ahead of print]
2. National Institutes of Health. Estrogen therapy has no long-term effect on cognition in younger postmenopausal women [press release]. Available at: http://www.nih.gov/news/health/jun2013/nia-24.htm. Accessed July 12, 2013.