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

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

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Abstract

Objective:: The Womens 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 α = 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.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalNeurology
Volume72
Issue number2
DOIs
StatePublished - Jan 13 2009

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Conjugated (USP) Estrogens
Cerebrovascular Disorders
Women's Health
Hormones
Medroxyprogesterone Acetate
Placebos
Therapeutics
Dementia
Brain
Basal Ganglia
Cognition
Linear Models
Cardiovascular Diseases
Cross-Sectional Studies
Smoking
Outcome Assessment (Health Care)
Hypertension

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Coker, L. H., Hogan, P. E., Bryan, N. R., Kuller, L. H., Margolis, K. L., Bettermann, K., ... Shumaker, S. A. (2009). Postmenopausal hormone therapy and subclinical cerebrovascular disease: The WHIMS-MRI Study. Neurology, 72(2), 125-134. https://doi.org/10.1212/01.wnl.0000339036.88842.9e

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.

In: Neurology, Vol. 72, No. 2, 13.01.2009, p. 125-134.

Research output: Contribution to journalArticle

Coker, LH, Hogan, PE, Bryan, NR, Kuller, LH, Margolis, KL, Bettermann, K, Wallace, RB, Lao, Z, Freeman, R, Stefanick, ML & Shumaker, SA 2009, 'Postmenopausal hormone therapy and subclinical cerebrovascular disease: The WHIMS-MRI Study', Neurology, vol. 72, no. 2, pp. 125-134. https://doi.org/10.1212/01.wnl.0000339036.88842.9e
Coker LH, Hogan PE, Bryan NR, Kuller LH, Margolis KL, Bettermann K et al. Postmenopausal hormone therapy and subclinical cerebrovascular disease: The WHIMS-MRI Study. Neurology. 2009 Jan 13;72(2):125-134. https://doi.org/10.1212/01.wnl.0000339036.88842.9e
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. / Postmenopausal hormone therapy and subclinical cerebrovascular disease : The WHIMS-MRI Study. In: Neurology. 2009 ; Vol. 72, No. 2. pp. 125-134.
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AU - Coker, L. H.

AU - Hogan, P. E.

AU - Bryan, N. R.

AU - Kuller, L. H.

AU - Margolis, K. L.

AU - Bettermann, K.

AU - Wallace, R. B.

AU - Lao, Z.

AU - Freeman, R.

AU - Stefanick, M. L.

AU - Shumaker, S. A.

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N2 - Objective:: The Womens 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 α = 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.

AB - Objective:: The Womens 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 α = 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.

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