Published Online
on May 17, 2007

A more recent version of this article appeared on July 1, 2007

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Submitted on December 15, 2006
Revised on January 19, 2007
Accepted on January 22, 2007

Neurocognitive Outcomes Are Not Improved by 17-Estradiol in Postmenopausal Women Undergoing Cardiac Surgery

Charles W. Hogue Jr MD^*; Kenneth Freedland PhD; Tamara Hershey PhD; Robert Fucetola PhD; Abullah Nassief MD; Benico Barzilai MD; Betsy Thomas RN; Stanley Birge MD; David Dixon MS; Kenneth B. Schechtman PhD; and Victor G. Dávila-Román MD

From the Department of Anesthesiology and Critical Care Medicine (C.W.H., Jr), Johns Hopkins University Medical School, Baltimore, Md; the Departments of Psychiatry (K.F., T.H., S.B.) and Neurology (R.F., A.N.), the Cardiovascular Division, Department of Medicine (B.B., V.G.D.-R.), the Department of Anesthesiology (B.T.), and the Division of Biostatistics, Department of Medicine (D.D., K.B.S.), Washington University School of Medicine, St. Louis, Mo.

^* To whom correspondence should be addressed. E-mail: chogue2{at}jhmi.edu.

Background and Purpose--Neurocognitive dysfunction is an important source of patient morbidity and mortality after cardiac surgery that may disproportionately affect postmenopausal women. 17-Estradiol limits the extent of ischemic neuronal injury in a variety of experimental models. The purpose of this study was to evaluate whether perioperative administration of 17-estradiol to postmenopausal women reduces the frequency of neurocognitive dysfunction after cardiac surgery.

Methods--One hundred seventy-four postmenopausal women not on estrogen replacement therapy who were undergoing primary coronary artery bypass graft surgery and/or valve surgery with cardiopulmonary bypass were prospectively randomized to receive in a double-blinded manner either 17-estradiol or placebo beginning the day before surgery and continuing for 5 days postoperatively. The patients were evaluated before and after surgery with the National Institutes of Health Stroke Scale and a psychometric test battery.

Results--There were no differences in the frequency of neurocognitive dysfunction (primary outcome) between patients randomized to perioperative 17-estradiol (n=86) and those randomized to placebo (n=88) 4 to 6 weeks after surgery (17-estradiol, 22.4% versus placebo, 21.4%, P=0.45). The mean scores on tests of psychomotor speed were worse in women in the 17-estradiol group than in the placebo group at the 4- to 6-week (P=0.005) postoperative testing sessions.

Conclusions--Perioperative treatment with 17-estradiol did not result in improved neurocognitive outcomes in postmenopausal women undergoing cardiac surgery.

Key words: cardiac surgery • cognitive impairment • estrogen • neuroprotective agents

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