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

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.

SUBMITTER: Espeland MA

PROVIDER: S-EPMC6075542 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Espeland Mark A MA Rapp Stephen R SR Manson JoAnn E JE Goveas Joseph S JS Shumaker Sally A SA Hayden Kathleen M KM Weitlauf Julie C JC Gaussoin Sarah A SA Baker Laura D LD Padula Claudia B CB Hou Lifang L Resnick Susan M SM

The journals of gerontology. Series A, Biological sciences and medical sciences 20170601 6

<h4>Background</h4>Postmenopausal hormone therapy may have long-term effects on cognitive function depending on women's age.<h4>Methods</h4>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 ...[more]

PMID: 27506836

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Project description:IMPORTANCE:Postmenopausal hormone therapy with conjugated equine estrogens (CEEs) may adversely affect older women’s cognitive function. It is not known whether this extends to younger women. OBJECTIVE:To test whether prescribing CEE-based hormone therapy to postmenopausal women aged 50 to 55 years has longer-term effects on cognitive function. DESIGN:Trained, masked staff assessed participants with an annual telephone-administered cognitive battery that included measures of global and domain-specific cognitive functions. Cognitive testing was conducted an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years, and repeated 1 year later. Enrollment occurred from 1996 through 1999. SETTING:Forty academic research centers. PARTICIPANTS:The study population comprised 1326 postmenopausal women, who had begun treatment in 2 randomized placebo-controlled clinical trials of hormone therapy when aged 50 to 55 years. INTERVENTION:The clinical trials in which the women had participated had compared 0.625 mg CEE with or without 2.5 mg medroxyprogesterone acetate over a mean of 7.0 years. MAIN OUTCOMES AND MEASURES:The primary outcome was global cognitive function. Secondary outcomes were verbal memory, attention, executive function, verbal fluency, and working memory. RESULTS:Global cognitive function scores from women who had been assigned to CEE-based therapies were similar to those from women assigned to placebo: mean (95% CI) intervention effect of 0.02 (?0.08 to 0.12) standard deviation units (P = .66). Similarly, no overall differences were found for any individual cognitive domain (all P > .15). Prespecified subgroup analyses found some evidence that CEE-based therapies may have adversely affected verbal fluency among women who had prior hysterectomy or prior use of hormone therapy: mean treatment effects of ?0.17 (?0.33 to ?0.02) and ?0.25 (?0.42 to ?0.08), respectively; however, this may be a chance finding. CONCLUSIONS AND RELEVANCE:CEE-based therapies produced no overall sustained benefit or risk to cognitive function when administered to postmenopausal women aged 50 to 55 years. We are not able to address whether initiating hormone therapy during menopause and maintaining therapy until any symptoms are passed affects cognitive function, either in the short or longer term. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01124773.

Project description:ObjectiveIn a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships.MethodsWe evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships.ResultsControlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates.ConclusionsFindings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley & Sons, Ltd.

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

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

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