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Short-term effects of high-dose 17ß-estradiol in postmenopausal PD patients

A crossover study

From the Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke (Drs. Mouradian and Chase), National Institutes of Health, Bethesda, MD; the Kimberly H. Courtwright and Joseph W. Summers Institute of Metabolic Disease (Dr. Hyland and L.A. Arnold), Baylor University Medical Center, Dallas, TX; the Department of Neurology (Dr. Hyland), University of Texas Southwestern Medical Center, Dallas, TX; Research Center, C.H.U.M./St. Luc Campus (Dr. Blanchet), Montreal, Quebec, Canada; and Vanderbilt University Medical Center (Dr. Fang), Nashville, TN.

Address correspondence and reprint requests to Dr. Thomas N. Chase, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Building 10/Room 5C103, 10 Center Drive MSC 1406, Bethesda, MD 20892-1406.

OBJECTIVE: To examine the effect of 17ß-estradiol on the severity of the cardinal signs of PD in postmenopausal women.

BACKGROUND: Although the impact of estrogens on the manifestations of PD has not been subjected to rigorous study, their use is generally thought to be associated with a detrimental antidopaminergic effect.

METHODS: A double-blind, placebo-controlled, two-arm crossover study of high-dose transdermal 17ß-estradiol was conducted in eight postmenopausal women with mild to moderate PD, all but one of whom exhibited levodopa-induced dyskinesias. Patients were randomized initially to either hormonal treatment or placebo for 2 weeks, followed by a 2-week washout period, and then another 2-week crossover treatment period. Active treatment employed four skin patches each releasing 0.1 mg of estradiol daily, replaced every 2 to 3 days.

RESULTS: After 10 days of treatment a significant reduction was observed in the antiparkinsonian threshold dose of IV levodopa. Mean duration and magnitude of the antiparkinsonian response to threshold or high doses of levodopa were unchanged, and dyskinesia scores were unaltered during 17ß-estradiol treatment compared with placebo. No worsening in "on" time or motor ratings with estrogen treatment was documented.

CONCLUSIONS: 17ß-estradiol appears to display a slight prodopaminergic (or antiparkinsonian) effect without consistently altering dyskinesias. Standard postmenopausal replacement therapy with transdermal 17ß-estradiol is likely to be well tolerated by many female parkinsonian patients.

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