Volume 64, Issue 12 p. 2448-2456
Clinical Investigations

Effect of Reproductive History and Exogenous Hormone Use on Cognitive Function in Mid- and Late Life

Roksana Karim PhD, MBBS

Corresponding Author

Roksana Karim PhD, MBBS

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Atherosclerosis Research Unit, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Address correspondence to Roksana Karim, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 2001 N Soto St, SSB 210 B, Los Angeles, CA 90089. E-mail: [email protected]Search for more papers by this author
Ha Dang PhD

Ha Dang PhD

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

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Victor W. Henderson MD, MS

Victor W. Henderson MD, MS

Division of Epidemiology, Department of Health Research and Policy, Stanford University, Stanford, California

Department of Neurology and Neurosciences, Stanford University, Stanford, California

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Howard N. Hodis MD

Howard N. Hodis MD

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Atherosclerosis Research Unit, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Department of Pharmacology and Pharmaceutical Science, School of Pharmacy, University of Southern California, Los Angeles, California

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Jan St. John MPH

Jan St. John MPH

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Atherosclerosis Research Unit, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

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Roberta D. Brinton PhD

Roberta D. Brinton PhD

Department of Pharmacology and Pharmaceutical Science, School of Pharmacy, University of Southern California, Los Angeles, California

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Wendy J. Mack PhD

Wendy J. Mack PhD

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Atherosclerosis Research Unit, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

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First published: 07 November 2016
Citations: 46

Abstract

Objectives

To investigate the association between reproductive history indicators of hormonal exposure, including reproductive period, pregnancy, and use of hormonal contraceptives, and mid- and late-life cognition in postmenopausal women.

Design

Analysis of baseline data from two randomized clinical trials: the Women's Isoflavone Soy Health and the Early vs Late Intervention Trial of Estradiol.

Setting

University academic research center.

Participants

Naturally menopausal women (N = 830).

Measurements

Participants were uniformly evaluated using a cognitive battery and a structured reproductive history questionnaire. Outcomes were composite scores for verbal episodic memory, executive function, and global cognition. Reproductive variables included ages at pregnancies, menarche, and menopause; reproductive period; number of pregnancies; and use of hormones for contraception and menopausal symptoms. Multivariable linear regression was used to evaluate associations between cognitive scores (dependent variable) and reproductive factors (independent variables), adjusting for age, race and ethnicity, income, and education.

Results

On multivariable modeling, age at menarche of 13 and older was inversely associated with global cognition (P = .05). Last pregnancy after age 35 was positively associated with verbal memory (P = .03). Use of hormonal contraceptives was positively associated with global cognition (P trend = .04), and verbal memory (P trend = .007). The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition (P = .04) and executive function (P = .04).

Conclusion

In this sample of healthy postmenopausal women, reproductive life events related to sex hormones, including earlier age at menarche, later age at last pregnancy, longer reproductive period, and use of oral contraceptives are positively related to aspects of cognition in later life.