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

Mark A. Espeland, Roberta Diaz Brinton, Joann E. Manson, Kristine Yaffe, Christina Hugenschmidt, Leslie Vaughan, Suzanne Craft, Beatrice J. Edwards, Ramon Casanova, Kamal Masaki, Susan M. Resnick

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1131-1138
Number of pages8
Issue number13
StatePublished - Sep 29 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology


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