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

TitlePostmenopausal hormone therapy, type 2 diabetes mellitus, and brain volumes.
Publication TypeJournal Article
Year of Publication2015
AuthorsEspeland MA, Brinton RDiaz, Manson JAE, Yaffe K, Hugenschmidt C, Vaughan L, Craft S, Edwards BJ, Casanova R, Masaki K, Resnick SM
Corporate AuthorsWHIMS-MRI2 Study Group
Date Published2015 Sep 29
KeywordsAged, Diabetes Mellitus, Type 2, Estrogen Replacement Therapy, Estrogens, Conjugated (USP), Female, Follow-Up Studies, Gray Matter, Humans, Postmenopause, Randomized Controlled Trials as Topic

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.

Alternate JournalNeurology
PubMed ID26163429
PubMed Central IDPMC4603880
Grant ListHHSN268200464221C / / PHS HHS / United States
N01-WH-4-4221 / WH / WHI NIH HHS / United States
/ / Intramural NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D