Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study.
OBJECTIVE
To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.


METHODS
Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.


RESULTS
Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90).


CONCLUSIONS
Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.
Resnick
S M
SM
Laboratory of Personality and Cognition, Biomedical Research Center/04B317, Baltimore, MD 21224, USA. susan.resnick@nih.gov
Espeland
M A
MA
Jaramillo
S A
SA
Hirsch
C
C
Stefanick
M L
ML
Murray
A M
AM
Ockene
J
J
Davatzikos
C
C
D000367:Age Factors; D000368:Aged; D001284:Atrophy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D015984:Causality; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D004967:Estrogens; D004966:Estrogens, Conjugated (USP)