Keiko Kurita1, Victor W Henderson2, Margaret Gatz3, Jan St John4, Howard N Hodis5, Roksana Karim4, Wendy J Mack6. 1. Department of Population Health, School of Medicine, New York University, New York, New York. 2. Department of Health Research and Policy (Epidemiology) and Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, California. 3. Department of Psychology, University of Southern California, Los Angeles, California; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 4. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, California. 5. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, California. 6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: wmack@usc.edu.
Abstract
OBJECTIVE: To investigate the association between bilateral oophorectomy and cognitive performance in healthy, older women. DESIGN: Retrospective analysis of clinical trial data. SETTING: Academic research institution. PATIENT(S): Healthy postmenopausal women without signs or symptoms of cardiovascular disease or diabetes (n = 926). INTERVENTION(S): Randomized interventions (not the focus of this analysis) in analyzed trials included B-vitamins, soy isoflavones, oral estradiol, and matching placebos. MAIN OUTCOME MEASURE(S): Measures in five cognitive domains (executive functions, semantic memory, logical memory, visual memory, and verbal learning) and global cognitive function. RESULT(S): Using data from three clinical trials conducted under uniform conditions, bilateral oophorectomy and its timing were analyzed cross-sectionally and longitudinally in relation to cognitive function in linear regression models. Covariates included age, education, race/ethnicity, body mass index, trial, and randomized treatment (in longitudinal models). Duration of menopausal hormone use was considered as a possible mediator and effect modifier. Median age of oophorectomy was 45 years. When evaluating baseline cognition, we found that surgical menopause after 45 years of age was associated with lower performance in verbal learning compared with natural menopause. Evaluating the change in cognition over approximately 2.7 years, surgical menopause was associated with performance declines in visual memory for those who had an oophorectomy after 45 years of age and in semantic memory for those who had oophorectomy before 45 years of age compared with natural menopause. Oophorectomy after natural menopause was not associated with cognitive performance. Adjustment for duration of hormone use did not alter these associations. CONCLUSION(S): Cognitive associations with ovarian removal vary by timing of surgery relative to both menopause and age.
OBJECTIVE: To investigate the association between bilateral oophorectomy and cognitive performance in healthy, older women. DESIGN: Retrospective analysis of clinical trial data. SETTING: Academic research institution. PATIENT(S): Healthy postmenopausal women without signs or symptoms of cardiovascular disease or diabetes (n = 926). INTERVENTION(S): Randomized interventions (not the focus of this analysis) in analyzed trials included B-vitamins, soy isoflavones, oral estradiol, and matching placebos. MAIN OUTCOME MEASURE(S): Measures in five cognitive domains (executive functions, semantic memory, logical memory, visual memory, and verbal learning) and global cognitive function. RESULT(S): Using data from three clinical trials conducted under uniform conditions, bilateral oophorectomy and its timing were analyzed cross-sectionally and longitudinally in relation to cognitive function in linear regression models. Covariates included age, education, race/ethnicity, body mass index, trial, and randomized treatment (in longitudinal models). Duration of menopausal hormone use was considered as a possible mediator and effect modifier. Median age of oophorectomy was 45 years. When evaluating baseline cognition, we found that surgical menopause after 45 years of age was associated with lower performance in verbal learning compared with natural menopause. Evaluating the change in cognition over approximately 2.7 years, surgical menopause was associated with performance declines in visual memory for those who had an oophorectomy after 45 years of age and in semantic memory for those who had oophorectomy before 45 years of age compared with natural menopause. Oophorectomy after natural menopause was not associated with cognitive performance. Adjustment for duration of hormone use did not alter these associations. CONCLUSION(S): Cognitive associations with ovarian removal vary by timing of surgery relative to both menopause and age.
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