Androgen Effects On Cognition In Turner Syndrome

雄激素对特纳综合征认知的影响

• 批准号: 6733493
• 负责人: Judith L Ross
• 金额: $ 29.05万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6733493
• 关键词: Turner' s syndrome; adolescence (12-20); androgens; attention; behavioral /social science research tag; child behavior; clinical research; clinical trials; cognition; female; hormone therapy; human subject; human therapy evaluation; intelligence tests; learning; longitudinal human study; memory; neuropsychological tests; neuropsychology; psychomotor function; questionnaires; space perception; visual perception

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.

描述（由申请人提供）：雄激素是影响人类和动物脑发育和行为的激素。在青春期期间发生认知和行为变化，与女性和男性的性激素（雌激素和雄激素）水平显着增加。激素变化在建模成人大脑成熟的最后阶段中起着重要作用。特纳综合征（TS）的女孩缺少第二个X染色体的全部或一部分，出生于卵巢，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代表了一种独特的性激素缺陷模型，其中研究了雄激素治疗对女性认知和行为的生物学作用。正在进行的研究（NS32531）利用1）两年（开始时10-14岁）进行了四年：（a）雄激素治疗的和（b）NO雄激素（安慰剂）治疗的（安慰剂）治疗和2）年龄匹配，是年龄匹配的，正常的女性对照组，也随后持续了四年。此外，所有TS女孩（两个治疗组）在研究的第三年和第四年都接受了标准的雌激素替代疗法。我们建议继续并完成这项随机，双盲临床试验。当前研究的扩展标志着在关键的青春期中纵向监测四年雄激素治疗的影响的前所未有的机会。我们收集的数据表明，治疗的影响可能与组织因素有关，从而导致了很长一段时间的变化。目前尚不清楚观察到的增量变化是否继续还是平稳。该研究的扩展（四年）使每个孩子都能完成四年的治疗，将有助于确定这一点。 该项目的具体目的是：1）检查4年雄激素治疗对生长激素治疗的TS女孩认知和心理调整的影响，2）记录青春期TS女孩认知和行为功能的差异和相似性（与Androgen治疗或不接受Androgen）以及年龄和VIQ匹配的正常女孩，也遵循4岁。 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与未接受雄激素治疗的TS治疗的女孩相比，雄激素将在算术成就的测试中表现得更好，（4）具有雄激素治疗的女孩将在语言，执行功能和注意力的测试中类似地表现，与未经androgen的TS治疗相比，andRogen差异和andRogen差异的差异（5）（5）（5）（5）（5）（5）处理时间和算术学业表现会减少但不会随着时间的流逝而消失，这表明TS中的某些认知缺陷仅部分可逆，并且（6）经过雄激素治疗的TS主体和对手动良好运动速度测试的控制量会随着时间的推移和消失而消失，表明某些认知能力降低，表明防御能力是teciecienciencie nececreciencies n t t s s reversicies n eversie ne the the the the se nevipieciencie是the s reversicies n t t s n s n s reversience ne the the the the the the the the ts的性能差异。 对青少年认知和社会发展的拟议继续调查是理解正常脑发育的重要步骤。此外，这些数据将有助于确定如何在特纳综合征中优化认知功能，并将扩展对男性/女性认知二态性机制的知识。