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Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study


Coker, L. H., Hogan, P. E., Bryan, N. R., Kuller, L. H., Margolis, K. L., Bettermann, K., Wallace, R. B., Lao, Z., Freeman, R., Stefanick, M. L., Shumaker, S. A.


Neurology, Volume: 72, No.: 2, Pages.: 125-134

Year of Publication



Objective: The Women’s Health Initiative Memory Study (WHIMS) hormone therapy (HT) trials reported that conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA) increases risk for all-cause dementia and global cognitive decline. WHIMS MRI measured subclinical cerebrovascular disease as a possible mechanism to explain cognitive decline reported in WHIMS.; Methods: We contacted 2,345 women at 14 WHIMS sites; scans were completed on 1,424 (61%) and 1,403 were accepted for analysis. The primary outcome measure was total ischemic lesion volume on brain MRI. Mean duration of on-trial HT or placebo was 4 (CEE+MPA) or 5.6 years (CEE-Alone) and scans were conducted an average of 3 (CEE+MPA) or 1.4 years (CEE-Alone) post-trial termination. Cross-sectional analysis of MRI lesions was conducted; general linear models were fitted to assess treatment group differences using analysis of covariance. A (two-tailed) critical value of alpha = 0.05 was used.; Results: In women evenly matched within trials at baseline, increased lesion volumes were significantly related to age, smoking, history of cardiovascular disease, hypertension, lower post-trial global cognition scores, and increased incident cases of on- or post-trial mild cognitive impairment or probable dementia. Mean ischemic lesion volumes were slightly larger for the CEE+MPA group vs placebo, except for the basal ganglia, but the differences were not significant. Women assigned to CEE-Alone had similar mean ischemic lesion volumes compared to placebo.; Conclusions: Conjugated equine estrogen-based hormone therapy was not associated with a significant increase in ischemic brain lesion volume relative to placebo. This finding was consistent within each trial and in pooled analyses across trials.;

Bibtex Citation

@article{Coker_2009, doi = {10.1212/01.wnl.0000339036.88842.9e}, url = {}, year = 2009, month = {jan}, publisher = {Ovid Technologies (Wolters Kluwer Health)}, volume = {72}, number = {2}, pages = {125--134}, author = {L. H. Coker and P. E. Hogan and N. R. Bryan and L. H. Kuller and K. L. Margolis and K. Bettermann and R. B. Wallace and Z. Lao and R. Freeman and M. L. Stefanick and S. A. Shumaker}, title = {Postmenopausal hormone therapy and subclinical cerebrovascular disease: The {WHIMS}-{MRI} Study}, journal = {Neurology} }


adverse effects, age factors, aged, blood supply, brain, brain ischemia, causality, cerebral arteries, chemically induced, complications, data interpretation statistical, diagnosis, drug effects, estrogen replacement therapy, estrogens, estrogens conjugated usp, female, humans, hypertension, magnetic resonance imaging, methods, outcome assessment (health care), pathology, physiopathology, risk factors

Countries of Study


Types of Dementia

Dementia (general / unspecified)

Types of Study

Randomised Controlled Trial

Type of Outcomes

Risk reduction (of dementia and co-morbidities)

Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population