Interactions between estradiol, diabetes, and brain aging and the risk for cognitive impairment

Abstract

The Women’s Health Initiative Memory Study reported that older women using conjugated equine estrogens hormone therapy (HT) with or without medroxyprogesterone acetate were at increased risk for probable dementia and smaller brain volumes. These adverse effects were greatest among women who had type 2 diabetes mellitus (T2DM) at baseline or who developed the disease during follow-up. This review summarizes existing literature from randomized trials, observational studies, and preclinical studies to provide a fundamental understanding of the effects of the interaction between T2DM and HT on cognitive and metabolic health changes in brain aging.

摘要

妇女健康倡议记忆研究报告称, 使用结合雌激素进行激素疗法(HT)的老年妇女, 无论是否联合使用醋酸甲羟孕酮, 可能患痴呆症的风险都会增加, 大脑体积也会变小。这些不良反应在基线时既患有2型糖尿病(T2 DM)或在随访期间发展为2型糖尿病的女性中最大。本文综述了随机试验、观察性研究和临床前研究中的现有文献, 以期从根本上了解T2 DM和HT之间的相互作用对脑老化过程中认知和代谢健康变化的影响。

Keywords:

• Hormone therapy
• estradiol
• menopause
• cognition
• metabolism
• diabetes
• dementia
• bioenergetics

Potential conflict of interest

C.E.H., T.D., and M.A.E. have no relevant conflicts of interest to report.

Additional information

Funding

This work was supported by the NIA [grant 1R21AG054955]; M.A.E. received support from the NIA [Contract No. HHSN-271-2011-00004C], Wake Forest Alzheimer’s Disease Research Center [P30AG049638].