Androgen Effects On Cognition In Turner Syndrome

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DESCRIPTION (provided by applicant): Androgens are hormones that influence brain development and behavior in humans and animals. Cognitive and behavioral changes occur during puberty, in concert with marked increases in sex hormone (estrogen and androgen) levels in females and males. Hormonal changes play a significant role in modeling the final stages of maturation in the adult brain. Girls with Turner syndrome (TS) are missing all or part of the second X chromosome, are born with dysgenetic ovaries, and therefore lack ovarian estrogen and androgen before, during, and after puberty. TS represents a unique, sex hormone-deficient model in which to study the biological effects of androgen treatment on cognition and behavior in females. The ongoing study (NS32531) utilizes 1) two TS groups (ages 10-14 years at start) treated for four years: (a) androgen-treated and (b) no androgen (placebo)-treated and 2) an age-matched, normal female control group, also followed for four years. Additionally, all TS girls (both treatment groups) receive standard estrogen replacement therapy during the 3rd and 4th years of the study. We propose to continue and complete this randomized, double-blind clinical trial. Extension of the current study marks an unprecedented opportunity to monitor longitudinally the influence of four years of androgen treatment across a critical period of adolescence. The data we have collected suggest that the effects of treatment may be related to organizational factors, resulting in changes that evolve over an extended period of time. It is unclear at present whether observed incremental changes continue or plateau. The extension (four years) of the study to permit each child to complete the four years of treatment will help to determine this. The specific aims of this project are to: 1) examine the effects of 4 years of androgen treatment on cognition and psychological adjustment in growth hormone-treated TS girls, 2) document the differences and similarities in cognitive and behavioral function between adolescent TS girls (treated or not treated with androgen) and age- and VIQ-matched normal girls, also followed longitudinally for 4 years. Specifically, we hypothesize that: (1) Girls with TS, treated with androgen, will perform better on tests of fine motor speed involving the hand, compared to girls with TS not treated with androgen, (2) Girls with TS, treated with androgen, will perform faster on certain tests of spatial perception, involving mental transformation, compared to girls with TS not treated with androgen, (3) Girls with TS, treated with androgen, will perform better on tests of arithmetic achievement, an academic outcome, compared to girls with TS not treated with androgen, (4) Girls with TS, treated with androgen, will perform similarly on tests of language, executive function, and attention, compared to girls with TS not treated with androgen, (5) The cognitive differences between androgen-treated TS subjects and controls on tests of spatial perceptual processing time and arithmetic academic performance will diminish but not disappear over time, indicating that certain cognitive deficiencies in TS are only partially reversible, and (6) The performance differences between androgen-treated TS subjects and controls on tests of fine motor speed of the hand will diminish over time and disappear, indicating that certain cognitive deficiencies in TS are reversible. This proposed continuing investigation of adolescent cognitive and social development represents an important step in understanding normal brain development. In addition, these data will help determine how to optimize cognitive function in Turner syndrome and will extend knowledge of the mechanisms of male/female cognitive dimorphisms.