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Androgen-Responsive Aspects of Cognition in Girls with Turner Syndrome

Departments of Pediatrics (J.L.R.) and Rehabilitation (G.A.S.), Thomas Jefferson University, Philadelphia, Pennsylvania 19107; A. I. duPont Hospital for Children (J.L.R.), Wilmington, Delaware 19899; Department of Medicine (D.R.), Division of Neurology, Pennsylvania State College of Medicine at Hershey, Hershey, Pennsylvania 17033; Developmental Endocrinology Branch (P.F., C.B., G.B.C.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; and Biomedical Computer Research Institute (H.K.), Philadelphia, Pennsylvania 19115

Address all correspondence and requests for reprints to: Judith L. Ross, M.D., Thomas Jefferson University, Department of Pediatrics, Suite 726, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. E-mail: Judith.Ross{at}mail.tju.edu.

Turner syndrome (TS) represents a unique, sex hormonedeficient model in which to study the biological effects of androgen treatment (replacement) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian androgen and estrogen production. We investigated the effects of androgen replacement therapy in TS girls, ages 10–14 yr, on cognitive function. A total of 64 TS girls were randomized to receive oxandrolone or placebo for 2 yr. They had a cognitive evaluation of four domains (verbal abilities, spatial cognition, executive function, and working memory) at baseline, 1, and 2 yr of the study. In addition, all subjects were examined for study safety every 6 months.

Three of the four domains studied did not change significantly in response to oxandrolone treatment (verbal abilities, spatial cognition, and executive function). In contrast, the working memory summary score had a significant group by time interaction. The oxandrolone-treated group demonstrated improved performance after 2 yr, compared with the placebo group (P < 0.03). Minimal or no side effects were observed. In conclusion, oxandrolone treatment for 2 yr improves working memory in adolescent girls with TS. What this degree of improvement will mean in real life terms for TS girls remains to be determined.

This work was supported in part by National Institutes of Health Grant NS32531.

Present address for G.B.C.: Eli Lilly & Co., Lilly Corporate Center Drop Code 2055, Indianapolis, Indiana 46285-2055.

Abbreviations: IQ, Intelligence quotient; SES, socioeconomic status; SGPT, serum glutamate pyruvate transaminase; TS, Turner syndrome; WISC-R, Wechsler Intelligence Scale for Children-Revised.

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