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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
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Freund, Lisa S
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University of Oklahoma Health Sciences Center
Schools of Medicine
Oklahoma City
United States
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Wisniewski, Amy B; Espinoza-Varas, Blas; Aston, Christopher E et al. (2014) Otoacoustic emissions, auditory evoked potentials and self-reported gender in people affected by disorders of sex development (DSD). Horm Behav 66:467-74