Improving Outcomes in DSD

描述(由申请人提供)：欧洲儿科内分泌学学会(ESPE)和劳森·威尔金斯儿科内分泌学会(LWPES)关于两性疾病管理的联合共识小组最近报告称，性发育障碍(DSD)中性别认同的决定因素仍有许多有待澄清。10历史上，受性发育障碍(DSD)影响的新生儿被分配抚养的性别主要是基于他们外生殖器的外观；(1)这决定了什么外科手术是整容重建的最佳手术，以及(2)生殖器组织被用作生物标记物，间接确定中枢神经系统在产前发育期间产生的雄激素暴露的程度。最近的长期结果研究表明，出生时外生殖器的外观在高达25%的时间内无法预测DSD患者的性别发育。如果可以确定新的、非侵入性的性别发育预测指标，与生殖器表型和遗传性别一起使用，那么这些将增加医生的工具箱，以改善受影响的个人的预后。因此，拟议的研究将测量人类听觉系统的性别和性二型性特征，这些特征受到产前雄激素暴露的影响，这些人患有DSD和养育女性。年龄匹配的不受DSD影响的男性和女性将作为对照。性别发展将通过有效和可靠的问卷进行评估。对听觉系统的测量将包括耳声发射(OAEs)和听觉诱发电位(AEP)。我们将确定OAEs和AEPs是否提高了我们预测DSD患者性别发育的能力，并结合更传统的标记，如生殖器表型和核型。建议的研究符合NICHD的使命，即促进对性心理发展决定因素的了解，以便受DSD影响的人对他们的医疗管理更满意，从而改善他们获得健康、富有成效的生活的机会。 公共卫生相关性：需要了解养育女性的性发育障碍(DSD)患者的性别焦虑症的风险因素，以及新的生理措施与更传统的测量方法(如生殖器表型和核型)相结合预测性别发育的可能性，以改善受DSD影响的患者的预后。我们建议确定使用中枢神经系统的非侵入性测量来预测DSD养育女性的性别发育的能力。这些知识将被证明对优化治疗决策有用，例如为那些在遗传、性腺和表型性别之间表现出不一致的人进行性别分配。

DESCRIPTION (provided by applicant): The joint European Society of Pediatric Endocrinology (ESPE) and Lawson Wilkins Pediatric Endocrine Society (LWPES) Consensus Group on the Management of Intersex Disorders recently reported that Much remains to be clarified about the determinants of gender identity in disorders of sex development.10 Historically, newborns affected by disorders of sex development (DSD) have been assigned a sex of rearing based largely on the appearance of their external genitalia because; (1) this dictated what surgical procedures were optimal for cosmetic reconstruction, and (2) the genital tissue was used as a biomarker to indirectly determine the degree of androgen exposure that the central nervous system incurred during prenatal development. Recent long-term outcome studies reveal that the appearance of the external genitalia at birth fails to predict gender development in people with DSD up to 25% of the time. If novel, non-invasive predictors of gender development could be identified for use in conjunction with genital phenotype and genetic sex, then these would add to a physician's toolkit to improve outcomes for affected individuals. Thus, the proposed studies will measure gender, and sexually dimorphic characteristics of the human auditory system that are influenced by prenatal androgen exposure in people with DSD and reared female. Age-matched males and females not affected by DSD will serve as control subjects. Gender development will be assessed with a battery a valid and reliable questionnaires. Measures of the auditory system will include otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs). We will determine if OAEs and AEPs improve our ability to predict gender development, in conjunction with more traditional markers such as genital phenotype and karyotype, in people with DSD. The proposed studies fit well with NICHD's mission to advance knowledge about the determinants of psychosexual development so that people affected by DSD have improved satisfaction with their medical management, thus improving their chance for healthy, productive lives. PUBLIC HEALTH RELEVANCE: Knowledge about the risk factors for gender dysphoria in people with disorders of sex development (DSD) reared female, and the potential for novel physiological measures in combination with more traditional measures such as genital phenotype and karyotype, to predict gender development is needed to improve outcomes in patients affected by DSD. We propose to identify the ability of using non-invasive measures of the central nervous system to predict gender development in people with DSD reared female. Such knowledge will prove useful in optimizing treatment decisions such as sex assignment for people who show discordance between their genetic, gonadal and phenotypic sex.