Endogenous estradiol levels indicated stroke risk in older postmenopausal women
Older postmenopausal women with high endogenous free
estradiol levels had 2.3-fold greater odds of stroke, particularly women with
greater central adiposity, according to new study results.
“Potential mediators, including atherogenic
dyslipidemia, insulin resistance and inflammation, might underlie this
association,” researchers wrote in the study. “Whether estradiol,
independent of atherogenic adiposity, influences such mediators and stroke risk
needs to be determined.”
Researchers conducted a prospective, case-control study
of the Study of Osteoporotic Fractures. They compared baseline serum levels of
endogenous estradiol in 196 postmenopausal women who had a subsequent
first-ever atherogenic stroke with 219 randomly selected women who did not.
Women did not take estrogen at baseline.
The main outcome measure, free estradiol index, was
calculated by dividing total estradiol by sex hormone-binding globulin
concentrations measured in baseline serum.
Postmenopausal women who experienced a first-ever stroke
tended to be older, were more likely to smoke and drink alcohol and had a
greater mean waist circumference.
After a median eight years of follow-up, the odds of
atherogenic stroke increased with increasing free estradiol index quartiles,
independent of age (P=.007). Women with free estradiol index levels in
the highest quartile had an age-adjusted OR of 2.31 (95% CI, 1.28-4.17) for
stroke, compared with levels in the lowest quartile. When the researchers
excluded women who did not take estrogen therapy during the eight-year
follow-up (53 incident stroke; 11 controls), those in the highest free
estradiol index quartile had an age-adjusted OR of 2.38 (95% CI, 1.29-4.42).
Moreover, this association between estradiol levels and
stroke was even stronger in women with greater central adiposity
(P=.08). Women with a waist circumference that measured >88 cm (78
incident stroke; 73 controls) and free estradiol index levels in the highest
quartile had an OR of 6.27 (95% CI, 1.10-35.6), compared with those in the
lowest quartile. In contrast, women with a waist circumference <88 cm (117
incident stroke; 146 controls) and the highest estradiol levels had an OR of
1.4 (95% CI, 0.64-3.06).
Type 2 diabetes, C-reactive protein levels and
atherogenic dyslipidemia were deemed potential biological mediators of the
relationship between endogenous estradiol levels and stroke.
“Estrogen-altering agents might be harmful or
beneficial depending on endogenous estradiol levels, especially in women with
greater central adiposity,” the researchers said.
Lee JS. Arch Neurol. 2010;67:195-201.
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