Kolesinska Z, Ahmed SF, Niedziela M, Bryce J, Molinska-Glura M, Rodie M, Jiang J, Sinnott RO, Hughes IA, Darendelier 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, Nordenstrom A, Lachlan K, Alkhawari M, Chatelain P, Weintrob N. Pediatrics. 2014 Sep; 134(3):e710-5

DOI:10.1542/peds.2014-1088

Abstract

BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. 

METHODS: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score.

RESULTS: The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P < .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys.

CONCLUSIONS: Although there is an association between the external appearance of the genitalia and the choice of sex assignment, there are clear temporal trends in this practice pointing toward an increased likelihood of affected infants being raised as boys. The impact of this change in practice on long-term health outcomes requires additional focus.

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Summary

This report provides very suggestive evidence that clinical recommendations regarding gender assignment in disorders (differences) of sex development (DSD) have been steadily changing. Readers may interpret the findings as indicative of shifts in practice based on evidence of better outcomes following the newer approach. However, important gaps exist in our knowledge of the long-term medical, psychological, social, sexual and quality of life adjustments of individuals with DSD. This is true for the earlier era of care – mid 1950’s to early 1990’s – that emphasized the person’s potential for complete adult sexual functioning based on genital anatomy and is even more true of the new era in which there’s an apparent trend toward rearing children with XY sex chromosomes as boys despite poor masculinization of their genitals. In fact, the potential implication of modifying practice based on incomplete information is that, even with the best of intentions, outcomes may be poorer. In short, doing the opposite of what turned out to be less than ideal does not mean experiences for patients and their families will be better.

How should we address the gaps in our knowledge regarding the clinical management of DSD? First, we need to support the study of affected individuals across many years of their lives, as we do for other congenital conditions. The registry that provided the data for this study is a case in point; however, the information in the registry is more of a snapshot of the person’s medical and gender status at one point in time rather than a record of both medical and psychological information over time. We need to broaden what we examine and attend to in clinical care over years of medical/surgical care that may help us understand the factors that lead to better outcomes in terms of patient and family experience.

The study implies that earlier and more precise genetic diagnosis may result in better recommendations regarding gender assignment. While this may be true, there is good evidence from other congenital and chronic medical conditions that it’s critical to take into account how parents are educated and helped to understand and emotionally accept how their child was born with a condition that is largely unknown and unspoken of. Such factors may be as important as decisions regarding gender assignment or whether genital surgery is performed or withheld. We know from experience in managing other chronic medical conditions, in children or adults, that those conditions that provoke secrecy and stigma are those for which the quality of care and psychological adjustment of affected people and their families are poorer. This situation, unfortunately, characterizes the care of individuals with DSD and their families.

A key message that providers should take away from this report is that patients with DSD, whether XX or XY, should be cared for at centers where interdisciplinary health care teams exist. In addition to having the collective expertise required to comprehensively care for these patients and their families, they are more likely to understand the nuance and implication of research findings beyond simply, for example, the proportion of patients being assigned as either boys or girls when the child’s biological sex is uncertain. Beyond this, physicians and the general public need to understand that changing trends in care do not necessarily flow from good evidence to justify the change. There are many examples in medicine where new practices were introduced or old ones changed without adequate research and outcomes have been no better and, in some cases, even worse.

The authors importantly point out that the International DSD (I-DSD) registry was not designed as an epidemiologic registry and thus there may be many cases not included that do not support the reported trend. Also, as they correctly point out, it would be valuable to know more about the determinants (genetic, hormonal, anatomic, parent attitudes/preferences) of the gender assignment decision.

The U.S. has its own DSD registry: the DSD Translational Research Network (DSD-TRN) is a National Institute of Child Health and Human Development-sponsored consortium of academic medical centers with interdisciplinary health care teams that is extending discovery of the genetic causes of DSD, reducing variability in the description of and clinical care (medical and psychosocial) delivered to affected people and their families. With parents’/patients’ consent, all the information collected over time is entered into the registry. This approach holds the promise of delivering not only a summary of changing practice over time but also details of the determinants of that change.

Disclosures