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From the Department of Pediatrics (Dr. Ross), Thomas Jefferson University, Philadelphia, PA; the Neurology Department (Dr. Roeltgen), Pennsylvania State College of Medicine at Hershey, PA, and Susquehanna Health Systems, Williamsport, PA; the Developmental Endocrinology Branch (Dr. Feuillan), NICHD, NIH, Bethesda, MD; the Biostatistics Department (Dr. Kushner), Hahnemann University, Philadelphia, PA; and the Developmental Endocrinology Branch (Dr. Cutler), NICHD, NIH, Bethesda, MD.
Address correspondence and reprint requests to Dr. Judith L. Ross, Department of Pediatrics, Thomas Jefferson University, 1025 Walnut St., Philadelphia, PA 19107; e-mail: Ross4{at}jeflin.tju.edu
BACKGROUND: The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and visual-perceptual abilities, and impaired nonverbal more than verbal memory. We compared verbal and nonverbal memory in estrogen- and placebo-treated girls with TS (ages 7 to 9 years) and age-matched female controls.
METHODS: Children received either estrogen (ethinyl estradiol, 25 ng/kg/d) or placebo for 1 to 3 years (mean, 2.1 ± 0.9 years) in a randomized, double-blind study. Memory and language tasks administered included the Wechsler Intelligence Scale for Children–Revised, Digit Span (forward and backward), the Children’s Word List, the Denman Paragraph, the Peabody Picture Vocabulary Test, Boston Naming, immediate and delayed Recall of the Rey Complex Figure, Nonword Reading, Wide Range Achievement Test–Revised reading subtest, Verbal fluency, and the Token Test.
RESULTS: The estrogen-treated TS group performed better than the placebo-treated TS group for the Children’s Word List immediate and delayed recall and the Digit Span backwards test (p < 0.01 to 0.04), although the results were not significant after adjusting for multiple comparisons. The placebo-treated TS group performed less well than the controls for recall of Digit Span backward (p < 0.0001; placebo-treated, 2.8 ± 1.3; estrogen-treated, 3.4 ± 1.2; and controls, 4.2 ± 1.3) and immediate and delayed recall of the Children’s Word List (delayed recall, p < 0.0001; placebo-treated, 6.2 ± 3.1; estrogen-treated, 8.0 ± 2.9; and controls, 9.0 ± 2.9). Performance for these measures was similar for the estrogen-treated TS group and the control group.
CONCLUSIONS: Estrogen replacement therapy in young girls with Turner Syndrome is associated with improved verbal and nonverbal memory. The optimal patient age, dose, and duration of estrogen replacement require further study.
Key words: Turner syndrome—Estrogen—Cholinergic systems—Memory
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