Prospective study of endogenous circulating estradiol and risk of stroke in older women.
OBJECTIVE
To test the hypothesis that circulating endogenous estradiol is associated with stroke risk in older postmenopausal women. Stroke incidence increases after menopause, when endogenous estrogen levels fall, yet exogenous estrogen increases strokes in older postmenopausal women. The relation between endogenous estrogen and stroke is unclear.


METHODS
Prospective case-control study.


METHODS
Study of Osteoporotic Fractures.


METHODS
Women at least age 65 years (99% follow-up) who were not taking estrogen at baseline.


METHODS
Free estradiol index (FEI) was calculated by dividing total estradiol by sex hormone-binding globulin concentrations measured in banked baseline serum. Using logistic regression, odds ratios were estimated for a first-ever atherothrombotic stroke associated with endogenous FEI in 196 women who had a subsequent validated stroke (median follow-up, 8 years) compared with 219 randomly selected women who did not. Potential mediators were assessed in multivariable models.


RESULTS
The age-adjusted odds of atherothrombotic stroke increased with increasing FEI quartiles (P(trend) = .007). Women in the highest FEI quartile had an age-adjusted 2.31-fold (odds ratio, 2.31; 95% confidence interval, 1.28-4.17) higher odds than women in the lowest quartile. Women with greater central adiposity had a suggestively stronger association (P = .08). Atherogenic dyslipidemia, type 2 diabetes mellitus, and C-reactive protein level were potential mediators of this relation.


CONCLUSIONS
Endogenous estradiol level is an indicator of stroke risk in older postmenopausal women, especially in those with greater central adiposity. Potential mediators, including atherogenic dyslipidemia, insulin resistance, and inflammation, might underlie this association. Whether estradiol, independent of atherogenic adiposity, influences such mediators and stroke risk needs to be determined. Estrogen-altering agents might be harmful or beneficial depending on endogenous estradiol levels, especially in women with greater central adiposity.
Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, Department of Internal Medicine, University of California-Davis, 4150 V Street, Sacramento, CA 95817, USA. jswlee@ucdavis.edu
Jennifer S
JS
Lee
Kristine
K
Yaffe
Li-Yung
LY
Lui
Jane
J
Cauley
Brent
B
Taylor
Warren
W
Browner
Steven
S
Cummings
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood*; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D016017:Odds Ratio; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D020521:Stroke / Q000097:blood* / Q000209:etiology*; D011795:Surveys and Questionnaires
D012738:Sex Hormone-Binding Globulin; D004958:Estradiol