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Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen

Shaywitz, Sally E. MD1; Naftolin, Frederick MD, DPhil2; Zelterman, Daniel PhD3; Marchione, Karen E. MA1; Holahan, John M. PhD1; Palter, Steven F. MD2; Shaywitz, Bennett A. MD1,4


Objective: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability.

Design: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task.

Results: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group.

Conclusion: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.

Good evidence suggests that estrogen affects basic neural processes and cognitive function in animals, 1,2 but the influence of estrogen on cognitive function in humans, especially postmenopausal women, has been much more difficult to establish. Results to date from observational studies and clinical trials are far from consistent. 3,4 Such inconsistency may reflect differences in the ages of the women studied. For example, midlife women tend to show a positive effect of estrogen on cognitive function. 5–7 Studies in older populations have more varied results, with some indicating a positive influence of estrogen on cognitive function, 8–13 others failing to show an effect, 14–17 and still others falling somewhere in between. 18 In animals, the effects of estrogen on cognitive function are observed most strongly when the agent is first used. 19

Most of the published studies of the association of estrogen use and cognitive function have focused on memory as the principal outcome. To our knowledge, no previous study has specifically examined the effects of estrogen on women's reading ability. Several lines of investigation have led us to study the effects of estrogen on reading. One line of evidence relates to the sex differences between childhood and adult life in the prevalence rates for reading disability (dyslexia). In children, the prevalence rates for dyslexia are similar in girls and boys, 20 whereas in adults, men have higher rates. 21 A second line of evidence comes from the clinical experience of one of the authors (F.N.) concerning the frequency of complaints of cognitive difficulties, including short-term memory and difficulties in reading in postmenopausal women. 22

Still another line of investigation comes from an appreciation of the neural mechanisms common to both reading and working memory. In both spoken and written language, words are composed of smaller, basic particles of sound called phonemes. For example, the word “cat” is comprised of the three phonemes /k/ /a/ /t/. In reading, the reader must transform the letters on the page into these elemental sounds of language. 23 Current theories focus on the importance of phonemes in reading and in the genesis of reading difficulties. A large body of research indicates that, in verbal working memory, verbal information is held in temporary storage in the form of phonemes. The components of language and memory (eg, verbal working memory and articulatory speed 24–26) reported to be sensitive to the actions of estrogen have in common a reliance on the storage and manipulation of phonemes. Most recently, we have demonstrated that the inferior parietal lobule, a brain region specifically activated by phonologic tasks, shows increased activation in postmenopausal women taking estrogen, 5 leading us to suggest that estrogen's effects may be mediated through its actions on neural sites serving phonologically coded information. Accordingly, we hypothesized that, through its actions on phonologic processing, estrogen would exert a positive influence on reading in postmenopausal women.

From the 1Department of Pediatrics, 2Department of Obstetrics and Gynecology, 3Department of Epidemiology and Public Health, and 4Department of Neurology, Yale University School of Medicine, New Haven, CT.

Received August 23, 2002; revised and accepted January 23, 2003.

This work was supported by grants from the National Institute of Child Health and Human Development (PO1 HD 21888 and P50 HD25802), from the National Cancer Institute (P30 CA 16359), and by an award from the Donaghue Women's Health Investigator Program.

Address correspondence to: Sally E. Shaywitz, MD, Department of Pediatrics, Yale University School of Medicine, PO Box 333, New Haven, CT 06510-8064. E-mail:

©2003The North American Menopause Society