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Randomized Controlled Trial
. 2017 Jun 1;72(6):838-845.
doi: 10.1093/gerona/glw156.

Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups

Mark A Espeland  1 , Stephen R Rapp  2   3 , JoAnn E Manson  4 , Joseph S Goveas  5 , Sally A Shumaker  2 , Kathleen M Hayden  2 , Julie C Weitlauf  6 , Sarah A Gaussoin  1 , Laura D Baker  2 , Claudia B Padula  6   7 , Lifang Hou  8 , Susan M Resnick  9 ; WHIMSY and WHIMS-ECHO Study Groups
Affiliations
Randomized Controlled Trial

Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in Two Age Groups

Mark A Espeland et al. J Gerontol A Biol Sci Med Sci. .

Abstract

Background: Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.

Methods: Postintervention follow-up was conducted with annual cognitive assessments of two randomized controlled clinical trial cohorts, beginning an average of 6-7 years after study medications were terminated: 1,376 women who had enrolled in the Women's Health Initiative when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone acetate for those without prior hysterectomy (mean 5.4 years), or matching placebos.

Results: Hormone therapy, when prescribed to women aged 50-54 years, had no significant long-term posttreatment effects on cognitive function and on changes in cognitive function. When prescribed to older women, it was associated with long-term mean (SE) relative decrements (standard deviation units) in global cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and executive function of 0.054 (0.023), all p < .05. These decrements were relatively stable over time. Findings did not vary depending on the hormone therapy regimen, prior use, or years from last menstrual period. Mean intervention effects were small; however, the largest were comparable in magnitude to those seen during the trial's active intervention phase.

Conclusions: CEE-based hormone therapy delivered near the time of menopause provides neither cognitive benefit nor detriment. If administered in older women, it results in small decrements in several cognitive domains that remain for many years.

Keywords: Cognitive aging; Hormone therapy; Women’s health.

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Figures

Figure 1.
Figure 1.
(A) Mean composite cognitive function scores over time by cohort and intervention assignment: hormone therapy (HT) or placebo. (B) Mean Telephone Interview for Cognitive Status-Modified (TICS-m) scores over time by cohort and intervention assignment: HT or placebo.
Figure 1.
Figure 1.
(A) Mean composite cognitive function scores over time by cohort and intervention assignment: hormone therapy (HT) or placebo. (B) Mean Telephone Interview for Cognitive Status-Modified (TICS-m) scores over time by cohort and intervention assignment: HT or placebo.
See this image and copyright information in PMC

References

    1. Rapp SR, Espeland MA, Shumaker SA, et al. ; WHIMS Investigators Effect of estrogen plus progestin on global cognitive of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289:2663–2672. doi:10.1001/jama.289.20.2663 - PubMed
    1. Espeland MA, Rapp SR, Shumaker SA, et al. ; Women’s Health Initiative Memory Study Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004;291:2959–2968. doi:10.1001/jama.291.24.2959 - PubMed
    1. Espeland MA, Brunner RL, Hogan PE, et al. ; Women’s Health Initiative Study of Cognitive Aging Study Group Long-term effects of conjugated equine estrogen therapies on domain-specific cognitive function: results from the Women’s Health Initiative study of cognitive aging extension. J Am Geriatr Soc. 2010;58:1263–1271. doi:10.1111/j.1532-5415.2010.02953.x - PMC - PubMed
    1. Espeland MA, Tindle HA, Bushnell CA, et al. ; Women’s Health Initiative Memory Study Brain volumes, cognitive impairment, and conjugated equine estrogens. J Gerontol A Biol Sci Med Sci. 2009;64:1243–1250. doi:10.1093/gerona/glp128 - PMC - PubMed
    1. Vaughan L, Espeland MA, Snively B, et al. ; Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y) Study Group The rationale, design, and baseline characteristics of the Women’s Health Initiative Memory Study of Younger Women (WHIMS-Y). Brain Res. 2013;1514:3–11. doi:10.1016/j.brainres.2013.03.047 - PMC - PubMed

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