Gender identity disorder (GID) in childhood and GID in adolescence and adulthood are listed in the Diagnostic and Statistical Manual of Mental Health Disorders, Fourth Edition (DSM-IV). Diagnostic criteria for children with GID include a strong and persistent cross-sex identification, which is manifested by a desire to be the other sex, a preference to dress, act and play in the fashion of the other sex, and a preference for playmates of the other sex. Diagnostic criteria for adolescents with GID include a desire to be the other sex, a wish to live and be treated like the other sex, and discomfort with the natal sex .
The approach to GID in children and adolescence has been evolving over the past 35 years and remains in flux. In 1979, the World Professional Association for Transgender Health (WPATH) published the first standards of care for the treatment of GID in adulthood, including the use of cross-sex steroid and sex reassignment surgery for postpubertal patients. The DSM-III (1980) was the first to classify GID as a psychiatric disorder and separated the condition into three entities: gender identity disorder of childhood (GIDC), transsexualism (describing GID in adolescents and adults) and psychosexual disorder not elsewhere classified . In DSM-IV (1994), the previously separate diagnoses GDIC and transsexualism were collapsed into one diagnosis, GID, with specific criteria for children versus adolescents and adults . WPATH published guidelines in 2001 describing use of pubertal suppression in adolescence as a ‘fully reversible intervention’, cross-sex hormones as early as age 16 as a ‘partially reversible intervention’ and irreversible surgical interventions as early as age 18 . A Dutch protocol published in 2006 similarly outlined treatment of adolescents with pubertal suppression at the onset of development of secondary sex characteristics and initiation of cross-sex hormones at age 16 or older . In 2009, The Endocrine Society published clinical practice guidelines similar to the Dutch protocol, except for greater flexibility in the age of initiation of cross-sex hormones. The guidelines were co-sponsored by the European Society of Endocrinology, the European Society of Pediatric Endocrinology, the Lawson Wilkins Pediatric Endocrine Society and WPATH .
In actual practice, the approach to children and adolescents with GID is quite variable. Many factors contribute, namely societal discomfort with treatment of GID in the paediatric population, unfamiliarity with the clinical practice guidelines among mental health, primary care and endocrine providers, limited long-term data with regard to interventions, limited number of centres equipped to treat GID and variable insurance coverage for medical therapies.
This review outlines the recent literature regarding the management of GID in childhood and adolescence and categorizes the literature based on life-stage and pubertal status.
A brief review of the key terminology used in the context of GID is presented .
Biologic sex means the genetic, anatomic and hormonal determinants that define male and female.
Gender stands for the social and psychological constructs typically associated with biologic sex.
Gender role is defined as how a person presents himself/herself as masculine or feminine, and societal expectations of what it means to act masculine or feminine.
Gender attribution is defined as the process by which an observer assigns a sex to another person, or a person ‘passing’ for a certain sex.
Gender identity is defined as a person's own classification of self as a male or a female.
Sexual orientation is defined as the sex of the persons that one finds sexually desirable, homosexual versus heterosexual.
There have not been formal epidemiologic studies to assess the prevalence of GID in childhood. The Child Behavior Checklist (CBCL) has been used as a resource to estimate prevalence of sex variance in childhood . In reviews of American and Dutch CBCL, results from nonreferred patients, 5–12% of children had affirmative answers to items focusing on sex variance [8▪,9], which seems to decrease from ages 4–5 to ages 6–13 years .
There is a general agreement that children with strong and persistent cross-sex identification causing emotional distress should be evaluated by a mental health professional familiar with the diagnosis of GID. Mental health professionals use a variety of sex-identity specific tools and general assessments to aid in the diagnosis of GID and identification of coexisting comorbidities, recently reviewed by Zucker and Wood [10▪].
The majority of children diagnosed with GID appear to ‘desist’ and identify with their biologic sex by early adolescence or adulthood. The percentage of ‘persisters’ appears to be between 10 and 27% [11–13]. A qualitative study of adolescents diagnosed with GID in childhood explored the issue of persisting versus desisting GID. Persisters and desisters both felt that the period between age 10 and 13 was a critical time when they became aware of the persistence or desistence of their sex dysphoria . Although GID diagnosed in children more commonly desists than persists, there have been reported associations with childhood GID and homosexuality in adolescents and adulthood. A Dutch prospective study analyzed data from the CBCL in 1983 and a sexual orientation questionnaire in 2007. For both men and women, adult homosexuality was 8–15 times higher in persons with sex variance in childhood [8▪].
There is no consensus among mental health professionals regarding appropriate intervention, or even appropriate goals of intervention, for children diagnosed with GID. General agreement does exist that avoidance of adult homosexuality is not an appropriate goal in the treatment of GID, as homosexuality is not defined as a psychiatric disorder. Zucker et al. [15▪] advocate a developmental and biopsychosocial model of treatment. Goals for treatment are formulated on a case-by-case basis, but may include reduction in sex dysphoria and acceptance of the biologic sex [15▪]. The Dutch approach to GID in childhood is not focused on reducing sex dysphoria, but rather on treating emotional, behavioural and family problems that may contribute [16▪]. Hill et al.  advocate an affirmative intervention, helping parents to support their child's declared sex rather than attempting to have the child conform to their natal sex. There is an increasing parental support for young children living as their desired sex; however, desisters may struggle with returning to live as their natal sex when their original desire to live as the opposite sex had been so strongly supported and encouraged by parents and providers, and even accepted by peers. . The Endocrine Society's 2009 clinical practice guidelines oppose complete social role change in prepubertal children with GID .
Although it is more common for children with GID to have desisting rather than persisting sex dysphoria, patients who persist into adolescence are unlikely to desist [19▪]. A Dutch protocol involving treatment with pubertal suppression at the beginning of puberty, cross-sex hormones not before age 16 and sex reassignment surgery not before age 18 was outlined by Delemarre-van de Waal and Cohen-Kettenis  in 2006.
In 2009, The Endocrine Society's clinical practice guidelines recommended that adolescents meeting eligibility and readiness criteria receive treatment to suppress puberty with GnRH analogues when they first exhibit signs of puberty. The criteria defining eligibility and readiness include a diagnosis of GID, puberty to at least Tanner stage 2, increased sex dysphoria at the arrival of puberty, absence of psychiatric comorbidities interfering with the diagnosis of GID, presence of adequate psychological and social support, and demonstration of understanding of expected outcomes, risks and benefits of therapy. The guidelines site both diagnostic and therapeutic rationales for pubertal suppression. Suppression allows time for the patient to socially transition to the desired sex and confirm the persistence of GID. In addition, adolescents with persisting GID often experience worsening sex dysphoria with the development of their undesired biologic puberty, and suppression can reduce this dysphoria. Finally, by suppressing puberty, the patient avoids irreversible body changes such as facial hair growth voice change, an Adam's apple and a male facial bone structure in boys, breast development in girls and body shape changes in both sexes. Patients who proceed through their natural puberty may have more difficulty ‘passing’ for their affirmed sex than patients who never experience the irreversible effects of puberty.
The Endocrine Society recommends the use of cross-sex steroids around age 16 to initiate pubertal development of the affirmed sex. In patients who have received cross-sex hormones, and who have had real-life experience living as the affirmed sex, sex reassignment surgeries and removal of gonads and the uterus can be considered after age 18 .
Since the publication of The Endocrine Society's guidelines, several authors have documented their experiences with GID treatment in adolescence. Spack et al. [20▪] describe the care of 97 patients at Boston Children's Hospital before and after the creation of a multidisciplinary Gender Management Service. Patients at this clinic receive treatment in concordance with The Endocrine Society's guidelines. The treatment population increased after the creation of the multidisciplinary clinic. A significant proportion of referred patients (44.3%) had a history of psychiatric diagnoses or mental health issues. Of the patients who started medical therapy, 19.6% were initially treated with GnRH analogues for pubertal suppression after presenting at Tanner stage 2 or 3. Approximately 69.6% of the patients were started on cross-sex hormone therapy after presenting at Tanner stage 4 or 5 [20▪,21].
de Vries and Cohen-Kettenis [16▪] report on management of sex dysphoria in children and adolescents at VU University Medical Center in Amsterdam. Between 35 and 50 children were referred to this centre each year from 2007 to 2011. Over the last decade, patients have been referred to this clinic at a progressively younger mean age. Patients are screened for concomitant psychiatric conditions, and when present, the patient is referred for psychological treatment. If eligible, patients receive pubertal suppression, followed by cross-sex hormones no younger than age 16 and surgical referrals no younger than age 18 [16▪].
de Vries et al. [19▪] presented a prospective follow-up study of the first 70 eligible candidates who received pubertal suppression between 2000 and 2008 at the VU University Medical Center. Psychological functioning and sex dysphoria were measured using six measurement tools prior to the start of pubertal suppression and again prior to the initiation of cross-sex hormones. There were improvements in behavioural and emotional problems, depressive symptoms and general functioning. Feelings of anxiety and anger, sex dysphoria or body satisfaction were not improved. None of the 70 patients withdrew from pubertal suppression therapy, and all started cross-sex hormone therapy when eligible [19▪].
A Dutch thesis by de Vries  examined 27 adults interviewed more than 1 year following sex reassignment surgery that was preceded by pubertal suppression and cross-sex hormone use. Interview data indicated resolved sex dysphoria and good quality of life .
Kreukels and Cohen-Kettenis [23▪] recently reviewed the debate on the use of GnRH analogues to suppress puberty in GID. The review compared arguments by those disapproving of medical intervention during adolescence with arguments by proponents of early treatment. The review suggests that published data seem to support early therapy for carefully selected patients, with benefits outweighing risks. However, the authors acknowledge that more systematic research is needed [23▪].
Cohen-Kettenis et al. [24▪] reported a follow-up to a case study published in 1998. The original case report described the use of a GnRH analogue to suppress the puberty of a 13-year-old girl with sex dysphoria. The patient received treatment with a GnRH analogue from ages 13 to 18 years, androgen therapy beginning at age 18 and later mastectomy, ovariectomy, hysterectomy and metoidioplasty. Follow-up evaluation was performed 22 years after initial presentation, at age 35. The patient did not regret the decision to suppress his natal female puberty and proceed with cross-sex steroids. He had a masculine appearance and had not experienced harassment due to his transsexualism. He had a normal psychiatric evaluation at the time of follow-up. He was not satisfied with his genital appearance and was considering phalloplasty. He had regrets about his lack of commitment in romantic relationships. The authors concluded that pubertal suppression and use of cross-sex steroids had a favourable outcome in this case [24▪].
BARRIERS TO TREATMENT
Despite The Endocrine Society management guidelines, the number of adolescents receiving the recommended medical interventions compared with the number of potentially eligible patients is quite low. In addition, the patients who do present to centres equipped to follow the guidelines often present late, after Tanner stage 3, making pubertal suppression less effective. Spack et al. [20▪] reviewed barriers to care that may be affecting when and if patients seek medical treatment. One is the continued classification of GID as a psychiatric condition. This classification may cause a lack of awareness among patients, parents and providers that GID may be treated with medical interventions in early adolescence. Another barrier is the high cost of medical therapy and limited insurance coverage. GnRH analogues may cost families $500–$1000 in monthly out-of-pocket expenses. This is not a barrier in some countries, including the Netherlands, where it is covered by a national health insurance. A third barrier is the limited number of centres currently offering treatment for adolescents with GID [20▪]. In addition, providers may lack familiarity with The Endocrine Society guidelines or may be hesitant to follow these guidelines, given limited long-term data supporting the safety and effectiveness of the guidelines. Finally, providers may have moral or philosophical objections to treating adolescents with GID with hormonal therapies.
Patients with GID have been treated at our Endocrine Division at Boston Children's Hospital since 1998. In 2007, this care was formalized with the creation of the Gender Management Service (GeMS) Clinic, a programme that serves both patients with GID and those with disorders of sexual development. The staff includes a paediatric endocrinologist, urologist, psychologist, psychiatrist and social worker. Our clinic follows the recommendations outlined in The Endocrine Society's clinical practice guidelines. We believe that treatment of adolescents with GID using these guidelines results in diminished sex dysphoria, improved psychological functioning, enhanced ability to ‘pass’ for the desired sex without expensive and unsatisfying cosmetic procedures and overall improved quality of life.
In reviewing the recent literature regarding the management of GID in childhood and adolescence, several areas requiring further study were identified.
The lack of consensus pertaining to the management of GID in young children presents parents and providers with a tremendous challenge. Further study defining the natural course of GID in childhood would be helpful. In addition, studies comparing different therapeutic strategies, for example encouragement versus discouragement of social transitioning during childhood, would have great importance.
As outlined in this review, there are several barriers to treatment for adolescents with GID. One important barrier may be the limited long-term data, which exist in support of The Endocrine Society guidelines. Recently published studies are beginning to present short-term data supporting pubertal suppression and cross-sex hormone use in adolescents [19▪,22]. One long-term follow-up case report is a welcome addition to the literature [24▪]. Large, long-term, follow-up reports are lacking. This is likely because the practices of pubertal suppression and cross-sex hormone use have not existed long enough for sufficient data to accumulate. As the adolescents treated with these interventions grow into adults, long-term follow up data will be critical for the future of this evolving field.
There has been no funding received for this article from the National Institutes of Health, Wellcome Trust, Howard Hughes Medical Institute or any other funding source.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 79).
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