Original Paper

HOR MON E RE SE ARCH I N PÆDIATRIC S

Received: September 14, 2015 Accepted: November 10, 2015 Published online: January 5, 2016

Horm Res Paediatr DOI: 10.1159/000442386

Gender Assignment, Reassignment and Outcome in Disorders of Sex Development: Update of the 2005 Consensus Conference Heino F.L. Meyer-Bahlburg a Katharine Baratz Dalke b Sheri A. Berenbaum c Peggy T. Cohen-Kettenis e Melissa Hines f Justine Marut Schober d  

 

a

 

 

 

 

New York State Psychiatric Institute and Department of Psychiatry, College of Physicians & Surgeons of Columbia University, New York, N.Y., b Department of Psychiatry, Hospital of the University of Pennsylvania, Philadelphia, Pa., c Departments of Psychology and Pediatrics, The Pennsylvania State University, University Park, Pa., and d Department of Pediatric Urology, University of Pittsburgh Medical Center Hamot, Erie, Pa., USA; e Department of Medical Psychology, VU Medical Center, Amsterdam, The Netherlands; f Department of Psychology, University of Cambridge, Cambridge, UK  

 

 

 

 

 

Abstract Background: Societal changes are increasingly moving the conceptualization of gender from a set of binary categories towards a bimodal continuum, which along with the cautious conclusions resulting from the 2005 Consensus Conference influences gender-related clinical work with patients with disorders of sex development. Objective: This article provides an update of these developments over the past decade along with an overview of pertinent new data. Conclusion: Considerably more research is needed on larger sample sizes with systematic long-term follow-up to ground the emerging trends in clinical management of the highly diverse disorders of sex development syndromes in a solid empirical basis. © 2016 S. Karger AG, Basel

© 2016 S. Karger AG, Basel 1663–2818/16/0000–0000$39.50/0 E-Mail [email protected] www.karger.com/hrp

Introduction

Assignment to one of the two options in the binary gender system is a key issue in the clinical management of newborns with genital ambiguity. The 2005 International Consensus Conference on Intersex [1] took place during a period of rapid change of gender perspectives and policies in Western post-industrial democracies, which is still continuing. This societal change increasingly affects clinical work with individuals expressing non-traditional gender behaviors and identities. Yet, the progress of psychological/psychiatric disorders of sex development (DSD) research is slow, largely due to the logistics associated with rare disorders. Empirical studies of long-term gender outcomes in individuals born with genital ambiguity have at best only marginally reached level B of the AGREE criteria, and recommendations for the psychosocial management usually represent level C [2]. Heino F.L. Meyer-Bahlburg, Dr. rer. nat. Department of Psychiatry, New York State Psychiatric Institute Columbia University Medical Center 1051 Riverside Drive, Unit 15, New York, NY 10032 (USA) E-Mail meyerb @ nyspi.columbia.edu

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Key Words Disorders of sex development · Gender assignment · Gender behavior · Gender identity · Gender reassignment

At the 2005 Consensus Conference the term ‘disorders of sex development’ was adopted with the input of two participating leading intersex activists [1]. Subsequently, however, others objected to ‘disorder’ as a stigmatizing label, and at present many activists and some clinicians use ‘differences of sex development’ as an alternative readout of the acronym [3]. As the present article focuses on individuals born with genital ambiguity, we employ the term DSD with this restriction implied, because not all of the psychosocial issues often associated with genital ambiguity apply to such syndromes as Turner’s and Klinefelter’s that are now included under the DSD category [1]. We use ‘sex’ in relation to somatic and physiological characteristics and ‘gender’ in relation to psychosocial aspects. Recent decades have seen a marked increase of clinical referrals of genitally typical people with gender dysphoria for psychological and medical assistance [4], and gender clinicians increasingly encounter individuals reporting gender identities other than male or female, such as ‘transgender’, ‘in-between’, ‘intersex’ or ‘genderqueer’ [5]. Identity diversification has also been noted in some studies of individuals with DSD [6, 7]. How much gender identity terms are proliferating in Western societies in general is illustrated by the social media giant, Facebook, which allows users to choose one of 58 identifiers, including ‘intersex’, or to enter their own custom identifiers [8]. Similarly, the American Psychiatric Association has recently gone beyond the traditional binary gender system by specifying as one of the indicators of gender dysphoria ‘a strong desire to be of the other gender (or some alternative gender different from one’s assigned gender)’ [9, p. 452]. Thus, gender is increasingly being conceptualized as a bimodal continuum rather than a binary-categorical system. The nature and causes of gender identity are increasingly seen as complex [10, 11]. Even the legal systems of several countries have begun to accommodate gender-atypical individuals by creating additional gender categories and liberalizing related regulations [12]. For instance, several countries in South Asia have broadened gender identifiers in official documents to legally recognize individuals known as hijras. Among hijras, trans women, or male-to-female transsexuals, are most heavily represented, but some individuals with DSD are also included [13]. In 2014, the Indian government established a non-male/non-female gender category for official government documents, including passports [14]. Similar changes were instituted in neighboring 2

Horm Res Paediatr DOI: 10.1159/000442386

countries, with Nepal, Pakistan and Bangladesh recognizing third genders by 2013 [15]. New Zealand and Australia now allow an ‘X’ identifier (for ‘indeterminate/unspecified’ gender) on passports following a simple declaration [16, 17]. The U.S. stopped requiring gonadectomy and genital surgery for a passport change of gender in 2011 [18]. As exemplified by Australia’s protection of ‘intersex’ in antidiscrimination legislation [19], the explicit recognition of human rights considerations in the care of individuals with DSD conditions is also spreading. In Europe, for instance, German law mandated in late 2013 that the sex category on birth certificates be left open in cases of newborns whose sex/gender cannot be determined, in the spirit of alleviating the pressure to reach a gender designation immediately [20]. That structural-level risk factors in terms of gender-related government policies and regulations are significantly associated with stigma experiences and long-term health outcomes has been documented in a variety of large-sample studies [21–23]. When discussing gender options, clinicians need to consider the legal regulation of the country they work in as well as the religious and other ideologies that can influence the gender perspectives of parents and patients, especially when those are immigrants or visitors from foreign countries. Many patients and parents will also be informed and influenced by discussions of gender ideologies and options on the internet. Thus, it is important to plan for both a detailed exploration of parents’ and patients’ viewpoints as well as their psychoeducation about gender and DSD issues.

Gender Assessment

A number of written questionnaires and structured interview guides have been validated in the context of the traditional binary view of gender [24, tables 2–4]. Now needed in addition are modifications of such tools for clinical gender assessment that place greater emphasis on the non-binary conceptualization of gender identity and facilitate acquisition of data for use within either framework. Some tools specifically assess gendered behavior or gender identity, others combine both, and clinicians should familiarize themselves with the content and not be misled by the names of the tools. As it is necessary to individualize gender decisions, standard questionnaires and interviews must be complemented by careful exploratory interviews with parents and patients. Preferably, such work is done by child psychologists or psychiatrists Meyer-Bahlburg  et al.  

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Conceptual Issues

Gender Development in Genitally Typical Children

In newborns with typical genitalia, gender assignment is based on the appearance of the external genitalia. Research on gender identity development in such children focuses on its cognitive aspects (knowledge about one’s own and others’ gender and use of that information) because children’s recognition and labeling of their own gender and of gender groups plays a role in their acquisition of gender-related characteristics, including attitudes, interests (e.g., toy choices) and personal-social attributes (e.g., aggression) [29]. During the first year of life, infants make discriminations between the genders based on voice and facial features, and begin to form stereotypes. Children start using gender labels at around 17–24 months of age, and the developing awareness of gender appears to contribute to their adoption of gender-typical behavior [29, 30]. Most children refer to themselves consistently as male or female by the age of 3 years. Yet, this work does not provide definitive information about when young children become aware of their own assigned gender, nor when they begin to identify (or not) with it, and how this varies with their general cognitive development. Much research also has documented the contribution to normative gender development of the social environment (e.g., parents, peers and media) through multiple mechanisms of social learning [31, 32]. Despite having unambiguously male or female genitalia, a small minority develop an incongruent gender. Most evidence about affective aspects of gender identity comes from the study of such children with gender-nonconforming (gender-atypical) behavior, gender dysphoria (unhappiness about the assigned gender) or transgender identity (identification with a gender other than the assigned one). Follow-up studies of (mostly clinic-referred) transgender children show that by the time of puberty the majority ‘desist’ and begin identifying with their natal or assigned gender, although many continue some degree of gender-atypical behavior and develop homoGender in Disorders of Sex Development

sexual attractions [33–35]. In contrast, those who remain transgender in adolescence are much more likely to ‘persist’ through adulthood [36]. The causes of such genderatypical developments are thought to include genetic, hormonal, cognitive and psychosocial factors [37]. The contribution of the last is suggested by evidence that early social transition to the experienced gender predicts persistence in transgender children [35] and that the assigned gender (or ‘sex of rearing’) is the best predictor of long-term gender identity in individuals with 46,XX congenital adrenal hyperplasia (CAH) [38]. Several findings on genitally typical children bear on gender assignment and development in children with DSD. (1) If gender reassignment is considered in young children after the first year of life, for instance in cases with delayed specification or correction of the DSD diagnosis, it will usually be several years before a consistent gender identity can be assessed [24]. (2) Gender identity is not present at birth, but develops gradually and may change over time; this is also seen in the development of patients with DSD [39, 40]. (3) The multidimensional nature of gender development makes it difficult to predict across gender characteristics. In particular, gender identity cannot simply be inferred from behaviors such as toy play, appearance or sexual attractions. This is particularly important to keep in mind if the child shows some atypical gender behavior. (4) Different aspects of gender develop along different trajectories under different influences; for example, parent socialization appears to play a dominant role in the formation of beliefs, whereas early hormones, socialization and cognitive processes shape toy preferences [31]. (5) Gender atypicality may present a psychological challenge and elicit social stigma, dependent on the specific social environment. Longitudinal data suggest that declines in adjustment across time are predicted by atypical gender identity. The combination of low gender typicality and high felt pressure may be particularly salient for the development of symptoms of anxiety and depression [41]. Therefore, coercion to change the emerging gender identity or gender expression of a child is considered harmful and unethical [26, 27].

Gender Development in Individuals with DSD

Gender behaviors and identities develop under the influence of multiple factors interacting over time. Numerous genes on sex chromosomes and autosomes as well as steroidal sex hormones present during fetal development and possibly also during early infancy play a role, along Horm Res Paediatr DOI: 10.1159/000442386

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who received some training in sexology, as offered in many Western countries by way of courses or workshops, and obtained an introduction into and supervision of clinical work with DSD patients, as offered at some DSDspecialized centers. In the context of current efforts to improve the multidisciplinary care for LGBT patients, related competence training is being widely disseminated [25–27], which also overlaps with the training needs of providers of DSD care [28].

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Horm Res Paediatr DOI: 10.1159/000442386

ior is of only moderate size and does not apply at all to syndromes involving non-hormonal genital malformations such as those occurring in cloacal exstrophy of the bladder or penile agenesis. Moreover, postnatal androgens may contribute to long-term gender outcome, both in early infancy [54] and at later stages, then perhaps mediated not only through organizational effects of sex hormones on the developing brain, but also through virilization of the body and associated effects on self-image and on the reactions of the social environment, as seen in cases of 46,XX CAH with poor hormonal control [47] and in untreated 5α-reductase-2 deficiency [55] and 17β-hydroxysteroid dehydrogenase-3 deficiency [56]. Such issues need to be considered in gender assignment decisions. Some studies highlight interactions between early hormones and experience in their effects on gendered behavior. For instance, females with CAH have been found to show enhanced (more male-typical) knowledge of geography [57], knowledge that can only be acquired through experience. Thus, androgen exposure appears to affect this outcome via psychosocial influences. In another recent study, parents of girls with CAH reported encouraging them to play in male-typical ways [58], probably because girls with CAH like to play in these ways and parents generally encourage activities that their children enjoy (unless the activities violate societal gender norms). In fact, parental encouragement was shown to partially mediate the association of CAH status with increased male-typical play. Thus, androgen exposure may affect the behavior of girls with CAH in part by indirectly influencing their social environment. Also, cultural factors play a role in gender development. For example, gender assignment of newborns with genital ambiguity to the male gender is often preferred in non-Western countries [59]. Presumably, such preferences in gender assignment are related to the relatively low social status of women in those countries.

Changes in Gender Assignment Policies for Newborns with Genital Ambiguity

In newborns with SRY-positive 46,XY genital ambiguity, decisions on gender assignment in Western countries have usually been strongly influenced by the degree of undermasculinization. This continues for cases of extreme undermasculinization such as 46,XY complete gonadal dysgenesis or 46,XY complete androgen insensitivity. Their external genitalia appear female at birth, and Meyer-Bahlburg  et al.  

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with diverse psychosocial factors. As demonstrated in animal research, testosterone and its derivatives have masculinizing and defeminizing neurobehavioral effects during early, sensitive periods of brain development [42]. In line with findings from research on non-human mammals, endocrine variations in prenatal development and early infancy in typically developing 46,XX and 46,XY individuals as well as the much more marked endocrine variations associated with genital ambiguity have increasingly provided evidence for the important role, directly or indirectly (see below), of prenatal androgens (but not estrogens) in the development of human gender-related behaviors, including sexual orientation and gender identity if assessed dimensionally [43, 44]. For example, 46,XY patients with complete gonadal dysgenesis and thereby complete prenatal deficiency of gonadal androgens are born with female-appearing external genitalia, are assigned to the female gender, express female-typical gender behavior and develop a female gender identity that is maintained in long-term followup [45]. 46,XY patients with complete androgen insensitivity usually have a similar trajectory, but recently a few cases with male assignment or reassignment have been reported [46], conceivably (but not proven) as a result of genetic mosaicism. On the other hand, 46,XX individuals with classical CAH are born with variable degrees of genital masculinization that reflect variable degrees of prenatal-androgen exposure from the adrenal glands, and the latter is correlated with the degree of masculinization of their gendered behavior, including their sexual orientation [47, 48]. Yet, if diagnosed early, 46,XX infants with CAH are usually assigned to the female gender because of their fertility potential as females. Most develop a female gender identity in the context of the binary gender system, and gender dysphoria and patient-initiated gender change to male are relatively rare [49, 50]. However, if measured as a continuous or dimensional variable, gender identity may correlate with indicators of androgen exposure, as was shown in two recent studies, one in 46,XX CAH [50] – in contrast to two earlier reports [51, 52] – and the other in a sample combining 46,XX and 46,XY children with several syndromes involving genital ambiguity [53]; the inconsistencies are yet to be explained. It also needs to be investigated under what circumstances an atypical gender identity measured dimensionally is to be interpreted as an indication for gender reassignment within the categorical gender system of a given society. The correlation of the genital masculinization status at birth with summary scales of later gender-related behav-

they are assigned to the female gender, which works well for almost all such individuals. As a consequence of the growing insights into the role of prenatal androgens in gender development, physicians are now more likely than before the 2005 consensus to assign to the male gender 46,XY newborns with presumably normal male prenatal androgen levels but non-hormonal genital malformations such as cloacal exstrophy of the bladder or penile agenesis [60, 61], although there remain marked regional variations in the approach [62]. Male assignment of 46,XY newborns with a normally configured (except for size) micropenis had already been recommended at the Consensus Conference [1]. The recent documentation of 12 reasonably well-adjusted cases of 46,XX CAH with high Prader scores of genital masculinization raised male, in combination with the known risks of feminizing genital surgery to cosmesis and sexual functioning, has led to a call for systematic consideration of male rearing of such newborns [63], despite the implied loss of fertility and necessity of lifelong androgen treatment. This recommendation could be strengthened if the reasons were established why 4 (12.1%) of a previously reviewed set of case reports of 33 46,XX individuals assigned male at birth later decided to change their gender to female [38]. It remains undisputed that the majority of individuals with intermediate degrees of prenatal androgenization and genital masculinization (in 46,XX) or undermasculinization (in 46,XY) appear to adjust to the assigned gender. However, still lacking are evidence-based recommendations for the various genital staging variables available, above or below which cut-off points an assignment to one gender is more successful than to the other, when considering both gender identity and quality of life outcomes. Gender assignment is particularly challenging in two syndromes of 46,XY individuals, 5α-reductase-2 deficiency and 17β-hydroxysteroid dehydrogenase-3 deficiency, both characterized by marked undermasculinization at birth, which frequently leads to female assignment, followed by marked virilization during puberty. Recent studies confirmed previous reports of a high rate of later patient-initiated gender change [55, 56], although the risk may be smaller if gonadectomy has been performed prior to puberty. Interestingly, in one study no actual gender change was reported in the diagnostic groups [64], but gender identities of participants were not all typically female. Even among participants who reported that they wanted to live in the female role, the authors found tendencies of increased male and transgender

identity, decreased female identity and high uncertainty about gender identity. Most of the cases with gender identity outcome reported to date came to clinical attention only after their pubertal development had started, and the patients were gonadectomized even later. Thus, systematic documentation is needed as to what extent prevention of somatic virilization by prepubertal castration also prevents gender dysphoria and patient-initiated gender change in these two syndromes. The existence of idiosyncratic clinician biases in gender decisions as well as the urgent need for an evidencebased consensus are illustrated by gender assignment in patients with ovotesticular syndrome. Regardless of karyotype, roughly half of such newborns are assigned to the female gender and the other half to the male gender [65]. Some clinicians are particularly influenced in their gender decisions by the location of the urethral meatus and the associated surgical challenges [66], while others are led to favor female assignment by the frequent presence of a uterus and normal ovarian tissue as compared to the more frequently dysgenetic testicular tissue [67]. It is not surprising, therefore, that a number of case reports show gender dysphoria and/or patient-initiated gender change in either direction in patients with ovotesticular syndrome [68, 69]. Only systematic long-term follow-up data on gender outcome and quality of life in sizeable samples will constitute a solid empirical basis for deciding on the crucial factors to consider in gender assignment decisions.

Gender in Disorders of Sex Development

Horm Res Paediatr DOI: 10.1159/000442386

Conclusion

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During the decade since the International Consensus Conference of 2005, there has been an increasing shift towards viewing gender as a continuum rather than as binary, with corresponding changes in societal regulations, although large variations within and across countries remain. Such societal changes, along with the specific aftereffects of the 2005 conference, also increasingly affect gender-related clinical work and underline the need for the involvement of interdisciplinary teams. However, there remains a great need for a systematic documentation of the factors influencing clinical decisions on gender assignment and reassignment as well as of long-term gender outcomes that can support the future development of truly evidence-based and more specific guidelines for clinical gender management.

References

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12 Byrne J: License to Be Yourself: Laws and Advocacy for Legal Gender Recognition of Trans People. New York, Open Society Institute, 2014. 13 Kalra G, Gupta S, Bhugra D: Sexual variation in India: a view from the west. Indian J Psychiatry 2010;52(suppl 1):S264–S268. 14 Khaleeli H: Hijra: India’s third gender claims its place in law. The Guardian, April 16, 2014. http://www.theguardian.com/society/2014/ apr/16/india-third-gender-claims-place-inlaw (accessed May 20, 2015). 15 Mae L: Hijras recognized as third gender in Bangladesh. 429 Magazine, November 13, 2013. http://dot429.com/articles/3467-hijrasrecognized-as-third-gender-in-bangladesh (accessed May 25, 2015). 16 Collins S: X marks the spot on passport for transgender travellers. The New Zealand Herald, December 5, 2012. http://www.nzherald. co.nz/nz/news/article.cfm?c_id=1& objectid=10852012 (accessed May 25, 2015). 17 New Australian passports allow third gender option. BBC, September 15, 2011. http:// www.bbc.com/news/world-asia-pacific14926598 (accessed May 25, 2015). 18 7 FAM 1300 Appendix M Gender Change. http://www.state.gov/documents/organization/143160.pdf (accessed August 20, 2015). 19 Sex discrimination amendment (sexual orientation, gender identity and intersex status) commencement proclamation 2013. https:// www.comlaw.gov.au/Details/F2013L01435 (accessed August 20, 2015). 20 Stafford N: Germany is first European country to recognise third sex on birth certificates. BMJ 2013;347:f5249. 21 Hatzenbuehler ML, Bellatorre A, Lee Y, Finch BK, Muennig P, Fiscella K: Structural stigma and all-cause mortality in sexual minority populations. Soc Sci Med 2014;103:33–41. 22 Perez-Brumer A, Hatzenbuehler ML, Oldenburg CE, Bockting W: Individual- and structural-level risk factors for suicide attempts among transgender adults. Behav Med 2015; 41:164–171. 23 Hatzenbuehler ML, Schwab-Reese L, Ranapurwala SI, Hertz MF, Ranirez MR: Associations between antibullying policies and bullying in 25 States. JAMA Pediatr 2015; 169: e152411. 24 Meyer-Bahlburg HFL: Gender monitoring and gender reassignment of children and adolescents with a somatic disorder of sex development. Child Adolesc Psychiatr Clin N Am 2011;20:639–649. 25 The Joint Commission: Advancing effective communication, cultural competence, and patient- and family-centered care for the lesbian, gay, bisexual, and transgender (LGBT) community. A field guide. 2011. http://www. jointcommission.org/assets/1/18/LGBTFieldGuide.pdf.

26 Adelson SL; American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI): Practice parameter on gay, lesbian, or bisexual sexual orientation, gender nonconformity, and gender discordance in children and adolescents. J Am Acad Child Adolesc Psychiatry 2012;51:957–974. 27 American Psychological Association: Guidelines for psychological practice with transgender and gender nonconforming people. www. apa.org/practice/guidelines/transgender.pdf (accessed October 18, 2015). 28 Cohen-Kettenis PT: Psychosocial and psychosexual aspects of disorders of sex development. Best Pract Res Clin Endocrinol Metab 2010;24:325–334. 29 Martin CL, Ruble DN: Patterns of gender development. Annu Rev Psychol 2010; 61: 353– 381. 30 Zosuls KM, Ruble DN, Tamis-LeMonda CS: Self-socialization of gender in African American, Dominican immigrant, and Mexican immigrant toddlers. Child Dev 2014; 85: 2202– 2217. 31 Blakemore JEO, Berenbaum SA, Liben LS: Gender Development. New York, Psychology Press/Taylor & Francis, 2009. 32 Bussy K: Gender identity development; in Schwartz SJ, Luyckx K, Vignoles VL (eds): Handbook of Identity Theory and Research. Volume 2: Domains and Categories. New York/Heidelberg/Dordrecht/London, Springer, 2012, pp 603–628. 33 Drummond KD, Bradley SJ, Peterson-Badali M, Zucker KJ: A follow-up study of girls with gender identity disorder. Dev Psychol 2008; 44:34–45. 34 Green R: The ‘Sissy Boy Syndrome’ and the Development of Homosexuality. New Haven, Yale University Press, 1987. 35 Steensma TD, McGuire JK, Kreukels BPC, Beekman AJ, Cohen-Kettenis PT: Factors associated with desistence and persistence of childhood gender dysphoria: a quantitative follow-up study. J Am Acad Child Adolesc Psychiatry 2013;52:582–590. 36 Cohen-Kettenis PT, Steensma TD, de Vries ALC: Treatment of adolescents with gender dysphoria in the Netherlands. Child Adolesc Psychiatr Clin N Am 2011;20:689–700. 37 Meyer-Bahlburg HFL: Sex steroids and variants of gender identity. Endocrinol Metab Clin North Am 2013;42:435–452. 38 Dessens AB, Slijper FME, Drop SLS: Gender dysphoria and gender change in chromosomal females with congenital adrenal hyperplasia. Arch Sex Behav 2005;34:389–397. 39 Meyer-Bahlburg HFL, Gruen RS, New MI, Bell JJ, Morishima A, Shimshi M, Bueno Y, Vargas I, Baker SW: Gender change from female to male in classical congenital adrenal hyperplasia. Horm Behav 1996;30:319–332.

Meyer-Bahlburg  et al.  

Downloaded by: NYU Medical Center Library 198.143.38.97 - 1/22/2016 6:06:56 PM

1 Lee PA, Houk CP, Ahmed SF, Hughes IA; International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology: Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics 2006;118:e488–e500. 2 AGREE Collaboration: Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Health Care 2003;12:18–23. 3 D’Alberton F, Assante MT, Foresti M, Balsamo A, Bertelloni S, Dati E, Nardi L, Bacchi ML, Mazzanti L: Quality of life and psychological adjustment of women living with 46,XY differences of sex development. J Sex Med 2015;12:1440–1449. 4 Aitken M, Steensma TD, Blanchard R, van der Laan DP, Wood H, Fuentes A, Spegg C, Wasserman L, Ames M, Fitzsimmons CL, Leef JH, Lishak V, Reim E, Takagi A, Vinik J, Wreford J, Cohen-Kettenis PT, de Vries AL, Kreukels BP, Zucker KJ: Evidence for an altered sex ratio in clinic-referred adolescents with gender dysphoria. J Sex Med 2015;12:756–763. 5 Kuper LE, Nussbaum R, Mustanski B: Exploring the diversity of gender and sexual orientation identities in an online sample of transgender individuals. J Sex Res 2012; 49: 244– 254. 6 Schweizer K, Brunner F, Schützmann K, Schönbucher V, Richter-Appelt H: Gender identity and coping in female 46, XY adults with androgen biosynthesis deficiency (intersexuality/DSD). J Couns Psychol 2009; 56: 189–201. 7 Warne G, Grover S, Hutson J, Sinclair A, Metcalfe S, Northam E, Freeman J; Murdoch Childrens Research Institute Sex Study Group: A long-term outcome study of intersex conditions. J Pediatr Endocrinol Metab 2005;18:555–567. 8 Wong CM: Facebook introduces gender freeform field for users. The Huffington Post, February 27, 2015. http://www.huffingtonpost.com/2015/02/26/facebook-gender-freeform-field-_n_6762458.html (accessed May 25, 2015). 9 American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, American Psychiatric Association, 2013. 10 Egan SK, Perry DG: Gender identity: a multidimensional analysis with implications for psychosocial adjustment. Dev Psychol 2001; 37:451–463. 11 Liben LS, Bigler RS: The developmental course of gender differentiation: conceptualizing, measuring, and evaluating constructs and pathways. Monogr Soc Res Child Dev 2002;67(2):i–viii, 1–147; discussion 148–183.

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51 Berenbaum SA, Bailey JM: Effects on gender identity of prenatal androgens and genital appearance: evidence from girls with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2003;88:1102–1106. 52 Meyer-Bahlburg HFL, Dolezal C, Baker SW, Carlson AD, Obeid JS, New MI: Prenatal androgenization affects gender-related behavior but not gender identity in 5- to 12-year-old girls with congenital adrenal hyperplasia. Arch Sex Behav 2004;33:97–104. 53 Chowdhury TK, Chowdhury MZ, Mili F, Hutson JM, Banu T: Gender identity shows a high correlation with Prader score in patients with disorders of sex development (DSD) presenting in mid childhood. Pediatr Surg Int 2014;30:527–532. 54 Pasterski V, Acerini CL, Dunger DB, Ong KK, Hughes IA, Thankamony A, Hines M: Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys. Horm Behav 2015;69:98–105. 55 Okeigwe I, Kuohung W: 5-Alpha reductase deficiency: a 40-year retrospective review. Curr Opin Endocrinol Diabetes Obes 2014; 21:483–487. 56 Chuang J, Vallerie A, Breech L, Saal HM, Alam S, Crawford P, Rutter MM: Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy? Int J Pediatr Endocrinol 2013;2013:15. 57 Berenbaum SA, Korman Bryk KL, Beltz AM: Early androgen effects on spatial and mechanical abilities: evidence from congenital adrenal hyperplasia. Behav Neurosci 2012; 126:86–96. 58 Wong WI, Pasterski VL, Hindmarsh PC, Geffner ME, Hines M: Are there parental socialization effects on the sex-typed behavior of individuals with congenital adrenal hyperplasia? Arch Sex Behav 2013;42:381–391. 59 Warne GL, Raza J: Disorders of sex development (DSDs), their presentation and management in different cultures. Rev Endocr Metab Disord 2008;9:227–236. 60 Diamond DA, Burns JP, Huang L, Rosoklija I, Retik AB: Gender assignment for newborns with 46XY cloacal exstrophy: a 6-year followup survey of pediatric urologists. J Urol 2011; 186:1642–1648.

Horm Res Paediatr DOI: 10.1159/000442386

61 Kolesinska Z, Ahmed SF, Niedziela M, Bryce J, Molinska-Glura M, Rodie M, Jiang J, Sinnott RO, Hughes IA, Darendeliler F, Hiort O, van der Zwan Y, Cools M, Guran T, Holterhus PM, Bertelloni S, Lisa L, Arlt W, Krone N, Ellaithi M, Balsamo A, Mazen I, Nordenström A, Lachlan K, Alkhawari M, Chatelain P, Weintrob N: Changes over time in sex assignment for disorders of sex development. Pediatrics 2014;134:e710–e715. 62 Josso N, Audi L, Shaw G: Regional variations in the management of testicular or ovotesticular disorders of sex development. Sex Dev 2011;5:225–234. 63 Lee PA, Houk CP, Husmann DA: Should male gender assignment be considered in the markedly virilized patient with 46,XX and congenital adrenal hyperplasia? J Urol 2010; 184:1786–1792. 64 Schweizer K, Brunner F, Handford C, Richter-Appelt H: Gender experience and satisfaction with gender allocation in adults with diverse intersex conditions (divergences of sex development, DSD). Psychol Sex 2014; 5: 56– 82. 65 Barseghyan H, Vilain E: The genetics of ovotesticular disorders of sex development; in New MI, Lekarev O, Parsa A, Yuen TT, O’Malley B, Hammer GD (eds): Genetic Steroid Disorders. London/Waltham/San Diego, Academic Press/Elsevier, 2014, pp 261–263. 66 Damiani D, Guedes DR, Damiani D, Setian N, Maciel-Guerra AT, Mello MP, Guerra-Júnior G: True hermaphroditism: experience with 36 patients (in Portuguese). Arq Bras Endocrinol Metabol 2005;49:71–78. 67 Nihoul-Fékété C: How to deal with congenital disorders of sex development in 2008 (DSD). Eur J Pediatr Surg 2008;18:364–367. 68 Jaruratanasirikul S, Engchaun V: Management of children with disorders of sex development: 20-year experience in southern Thailand. World J Pediatr 2014;10:168–174. 69 Sircili MHP, Denes FT, Costa EMF, Machado MG, Inacio M, Silva RB, Srougi M, Mendonca BB, Domenice S: Long-term follow-up of a large cohort of patients with ovotesticular disorder of sex development. J Urol 2014; 191: 1532–1536.

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40 Meyer-Bahlburg HFL, Migeon CJ, Berkovitz GD, Gearhart JP, Dolezal C, Wisniewski AB: Attitudes of adult 46,XY intersex persons to clinical management policies. J Urol 2004; 171:1615–1619. 41 Yunger JL, Carver PR, Perry DG: Does gender identity influence children’s psychological well-being? Dev Psychol 2004;40:572–582. 42 Hines M: Gender development and the human brain. Annu Rev Neurosci 2011; 34: 69– 88. 43 Berenbaum SA, Beltz AM: Sexual differentiation of human behavior: effects of prenatal and pubertal organizational hormones. Front Neuroendocrinol 2011;32:183–200. 44 Hines M, Constantinescu M, Spencer D: Early androgen exposure and human gender development. Biol Sex Differ 2015;6:3. 45 McCarty BM, Migeon CJ, Meyer-Bahlburg HFL, Zacur H, Wisniewski AB: Medical and psychosexual outcome in women affected by complete gonadal dysgenesis. J Pediatr Endocrinol Metab 2006;19:873–877. 46 Cadet P: Androgen insensitivity syndrome with male sex-of-living. Arch Sex Behav 2011; 40:1101–1102. 47 Meyer-Bahlburg HFL, Dolezal C, Baker SW, Ehrhardt AA, New MI: Gender development in women with congenital adrenal hyperplasia as a function of disorder severity. Arch Sex Behav 2006;35:667–684. 48 Meyer-Bahlburg HFL, Dolezal C, Baker SW, New MI: Sexual orientation in women with classical or non-classical congenital adrenal hyperplasia as a function of degree of prenatal androgen excess. Arch Sex Behav 2008;37:85– 99. 49 Meyer-Bahlburg HFL: Psychoendocrinology of congenital adrenal hyperplasia; in New MI, Lekarev O, Parsa A, Yuen TT, O’Malley B, Hammer GD (eds): Genetic Steroid Disorders. London/Waltham/San Diego, Academic Press/Elsevier, 2014, pp 285–300. 50 Pasterski VL, Zucker KJ, Hindmarsh PC, Hughes IA, Acerini CL, Spencer D, Neufeld S, Hines M: Increased cross-gender identification independent of gender role behavior in girls with congenital adrenal hyperplasia: results from a standardized assessment of 4- to 11-year-old children. Arch Sex Behav 2015; 44:1363–1375.

Gender Assignment, Reassignment and Outcome in Disorders of Sex Development: Update of the 2005 Consensus Conference.

Societal changes are increasingly moving the conceptualization of gender from a set of binary categories towards a bimodal continuum, which along with...
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