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Neurology. 2015 Sep 29;85(13):1131-8. doi: 10.1212/WNL.0000000000001816. Epub 2015 Jul 10.

Postmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.

Author information

1
From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD. mespelan@wakehealth.edu.
2
From the Departments of Biostatistical Sciences (M.A.E., R.C.), Internal Medicine (C.H., S.C.), and Social Sciences and Health Policy (L.V.), Wake Forest School of Medicine, Winston-Salem, NC; Departments of Pharmacology and Pharmaceutical Sciences, Biomedical Engineering, and Neurology (R.D.B.), University of Southern California, Los Angeles, CA; Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Departments of Epidemiology and Biostatistics, Psychiatry, and Neurology (K.Y.), University of California, San Francisco; Department of Internal Medicine (B.J.E.), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Geriatric Medicine (K.M.), University of Hawaii at Manoa, Honolulu, HI; and Laboratory of Behavioral Neuroscience (S.M.R.), Intramural Research Program, National Institute on Aging, NIH, Baltimore, MD.

Abstract

OBJECTIVE:

To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial.

METHODS:

The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes.

RESULTS:

Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p=0.002). This interaction was evident for total gray matter (p<0.001) and hippocampal (p=0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications.

CONCLUSIONS:

For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women.

PMID:
26163429
PMCID:
PMC4603880
DOI:
10.1212/WNL.0000000000001816
[Indexed for MEDLINE]
Free PMC Article

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