Children and adolescents in the Amsterdam Cohort of Gender Dysphoria: trends in diagnostic- and treatment trajectories during the first 20 years of the Dutch Protocol

Abstract

Background Twenty years ago, the Dutch Protocol—consisting of a gonadotropin-releasing hormone agonist (GnRHa) to halt puberty and subsequent gender-affirming hormones (GAHs)—was implemented to treat adolescents with gender dysphoria. Aim To study trends in trajectories in children and adolescents who were referred for evaluation of gender dysphoria and/or treated following the Dutch Protocol. Methods The current study is based on a retrospective cohort of 1766 children and adolescents in the Amsterdam Cohort of Gender Dysphoria. Outcomes Outcomes included trends in number of intakes, ratio of assigned sex at birth, age at intake, age at start of GnRHa and GAH, puberty stage at start of GnRHa, proportions of adolescents starting and stopping GnRHa, reasons for refraining from GnRHa, and proportions of people undergoing gender-affirming surgery. Results A steep increase in referrals was observed over the years. A change in the AMAB:AFAB ratio (assigned male at birth to assigned female at birth) was seen over time, tipping the balance toward AFAB. Age at intake and at start of GnRHa has increased over time. Of possibly eligible adolescents who had their first visit before age 10 years, nearly half started GnRHa vs around two-thirds who had their first visit at or after age 10 years. The proportion starting GnRHa rose only for those first visiting before age 10. Puberty stage at start of GnRHa fluctuated over time. Absence of gender dysphoria diagnosis was the main reason for not starting GnRHa. Very few stopped GnRHa (1.4%), mostly because of remission of gender dysphoria. Age at start of GAH has increased mainly in the most recent years. When a change in law was made in July 2014 no longer requiring gonadectomy to change legal sex, percentages of people undergoing gonadectomy decreased in AMAB and AFAB. Clinical Implications A substantial number of adolescents did not start medical treatment. In the ones who did, risk for retransitioning was very low, providing ongoing support for medical interventions in comprehensively assessed gender diverse adolescents. Strengths and Limitations Important topics on transgender health care for children and adolescents were studied in a large cohort over an unprecedented time span, limited by the retrospective design. Conclusion Trajectories in diagnostic evaluation and medical treatment in children and adolescents referred for gender dysphoria are diverse. Initiating medical treatment and need for surgical procedures depends on not only personal characteristics but societal and legal factors as well.

Interventions to suppress puberty in adolescents experiencing gender dysphoria or incongruence: a systematic review

“…There was evidence from multiple mainly pre-post studies that puberty suppression exerts its expected physiological effect, as previously demonstrated in children with precocious puberty 73. In adolescents experiencing gender dysphoria/incongruence, puberty suppression is initiated at different stages of puberty,74 and two studies found that the effects on secondary sex characteristics may vary depending on whether treatment is initiated in early puberty versus mid-puberty, with potentially different outcomes for birth-registered males and females 30 35. Multiple studies also found that bone density is compromised during puberty suppression, and gains in height may lag behind that seen in other adolescents.…”

“…Many studies reported effects of both puberty suppressants and hormones used in later adolescence for feminisation/masculinisation. In adolescents, GnRH-a often continues during hormone treatment,74 or for adolescents who do not receive puberty suppression, GnRH-a or other anti-androgens may be offered at initiation of hormones 66. This makes long-term follow-up of puberty suppression difficult to assess, including any differences between the types of interventions that are offered and when these are initiated, and the few studies reporting long-term outcomes either did not control for this or reported overall effects for both interventions.…”

“…This makes long-term follow-up of puberty suppression difficult to assess, including any differences between the types of interventions that are offered and when these are initiated, and the few studies reporting long-term outcomes either did not control for this or reported overall effects for both interventions. Although recent studies suggest nearly all adolescents who receive puberty suppression go on to feminising/masculinising hormones,74–76 research is still needed to assess whether suppression will have any lasting effects for those who do not. Aggregation of studies reporting proportions of adolescents who progress to hormones and reasons for discontinuation would also offer useful insights.…”

“…However, the findings are in line with previous reviews despite the inclusion of numerous additional studies. In an update of the National Institute for Health and Care Excellence evidence review of GnRH-a performed in April 2023,78 nine additional studies were identified, two of which they felt might materially affect their conclusions 72 74. One was already included in this review,72 and the other examined treatment trajectories which was not an outcome of interest 74…”

Masculinising and feminising hormone interventions for adolescents experiencing gender dysphoria or incongruence: a systematic review

“…Over the last decade, guidelines have broadened these criteria, for example, removing minimum age4 7 8 and making changes to the requirement of a diagnosis of gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders 5th edition, DSM-5), being replaced by gender incongruence (International Classification of Diseases 11th revision, ICD-11) 3. In a study of 1766 children and adolescents receiving care at a national gender service in the Netherlands (1997–2018), 202 birth-registered males and 454 birth-registered females received hormones at a median age of 16.0 (IQR 15.5–17.1) and 16.7 (16.0–17.5), respectively 9. In the UK, the mean age of consent for treatment was 17.3 (SD 0.1) 10…”