Androgen Effects On Cognition In Turner Syndrome

描述（由申请人提供）：雄激素是影响人类和动物大脑发育和行为的激素。认知和行为的变化发生在青春期，与性激素（雌性激素和雄性激素）水平的显著增加相一致。激素的变化在模拟成人大脑成熟的最后阶段中起着重要的作用。患有特纳综合征（TS）的女孩缺少全部或部分第二条X染色体，出生时卵巢发育不良，因此在青春期之前、期间和之后缺乏卵巢雌激素和雄激素。TS是一种独特的性激素缺乏模型，用于研究雄激素治疗对女性认知和行为的生物学影响。正在进行的研究（NS32531）使用1)两个TS组（开始时年龄为10-14岁）治疗4年：(a)雄激素治疗和（b)无雄激素（安慰剂）治疗，以及2）年龄匹配的正常女性对照组，也随访4年。此外，所有TS女孩（两个治疗组）在研究的第3年和第4年接受标准雌激素替代治疗。我们建议继续并完成这项随机、双盲的临床试验。目前研究的延伸标志着一个前所未有的机会，可以纵向监测四年雄激素治疗对青春期关键时期的影响。我们收集的数据表明，治疗的效果可能与组织因素有关，导致在较长一段时间内演变的变化。目前尚不清楚观察到的增量变化是继续还是平稳。延长（四年）的研究，以允许每个孩子完成四年的治疗将有助于确定这一点。

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.