Treatment trajectories among children and adolescents referred to the Norwegian National Center for Gender Incongruence

1 INTRODUCTION

Gender incongruence (GI) is defined as a marked and persistent incongruence between an individual's experienced gender and birth-assigned sex.¹ When GI causes clinically significant distress, it is called gender dysphoria (GD).² Gender-affirming treatment for children and adolescents with GI has been widely based on the Dutch Protocol.³ Implemented in the Netherlands from the late 1990s, the protocol introduced the early use of gonadotropin-releasing hormone agonists (GnRHa) to achieve puberty suppression in early stages of puberty, followed by gender-affirming hormonal treatment (GAHT) from the age of 16 years. Testosterone is initiated among persons assigned female gender at birth (AFAB) and oestrogen in persons assigned male gender at birth (AMAB). From the age of 18 years, surgical treatment can be initiated.

The evidence base that formed the Dutch Protocol has been challenged, most recently by the Cass Report which was initiated by the National Health Service in England.⁴ A series of systematic reviews outlining the report, along with three other recent systematic reviews,^5-8 highlight the low evidence of efficacy and safety in the medical treatment of children and adolescents with GI. Additionally, the phenomenon known as gender detransition is emerging.^9-14 In a recent literature review, prevalence estimates of detransition ranged from less than 1% to almost 30%, depending on definitions.¹¹

Most research from national gender clinics for children and adolescents has been conducted in the Netherlands. Studies report varying rates of GnRHa treatment (40%–63%), prevalence of GAHT (32%–85%) and high rates of continuation from GnRHa treatment to GAHT (98%) depending on inclusion criterias.^15-19 A study from the UK reported a similar continuation rate of 98%.²⁰ However, studies reporting on gender-affirming medical and surgical treatment among children and adolescents from national gender clinics are sparse, and the approach to the Dutch Protocol might differ between clinics.^{21, 22}

In Finland, England, Sweden and Norway, a more restrictive treatment approach has been recommended in recent years.^23-26 Professional discussions on the treatment approach for children and adolescents with GI would benefit from reports on trajectories across different gender clinics. This Norwegian study aims to present treatment trajectories for children and adolescents referred to the Norwegian National Center for Gender Incongruence (NCGI) at Oslo University Hospital (OUS) between 2000 and 2020. We aim to describe the proportion of the referred who (1) underwent gender-affirming medical and surgical treatment, (2) was prescribed GnRHa and GAHT (for each referral year), (3) started with GnRHa followed by GAHT, and (4) detransitioned until 2023. Additionally, we investigated the mortality rate and possible gender differences among the referred.

2 PARTICIPANTS AND METHODS

3 RESULTS

4 DISCUSSION

This study reports on trajectories among children and adolescents referred to the NCGI over two decades. Approximately one in five of the referred did not receive any gender-affirming medical treatment at the NCGI. Puberty suppression with GnRHa was initiated among 135/1258 (10.7%), significantly more AMAB than AFAB. Of those eligible, 95%–97% continued from GnRHa to GAHT. In total, 783/1258 (62.2%) started GAHT—significantly more AFAB than AMAB. Eighteen AFAB detransitioned after initiated GAHT, eleven were due to a cessation of transgender identity.

Of those who attended at least one appointment at the NCGI, 264/1198 (22.0%) were discharged without gender-affirming medical treatment. The most prevalent reason was a multidisciplinary decision to stop the assessment owing to mental health-related issues. A recently published article assessing mental health in the same sample of children and adolescents referred to the NCGI, found that 64.5% had one or more registered psychiatric diagnoses.³⁰

Desisting of transgender identity before initiating any gender-affirming medical treatment was registered in 62/1198 (5.2%) of those attending at least one appointment at the NCGI, as illustrated in Figure 1. Ristori et al. reported persistence rates from 2% to 39% among children with GD in studies conducted up until 2012, before the worldwide increase in referrals to gender clinics.³¹ Importantly, Ristori et al. report persistence rates in childhood GD. Little is known about desistance among those presenting with GI/GD in adolescence. A recent Dutch study on gender non-contentedness during adolescence and early adulthood found decreased gender non-contentedness with age.³² Unfortunately, our study could not differentiate between those with a childhood onset of GI/GD and those with adolescent onset in relation to desistance of transgender identity. Further research should investigate age differences in both onset of GI/GD and ages of desisting transgender identity. Our low desistence numbers might be related to the discussion on social transition as an active intervention possibly consolidating transgender identity,³³ as most children and adolescents referred to the NCGI have socially transitioned. Other factors explaining the high persistence rate could be the requirement of referrals from local child and adolescent psychiatric outpatient clinics (CAPOCs), which conduct initial assessments. This may reflect a higher intensity of GD in our sample. Additionally, some persons discharged from the NCGI due to mental health concerns or not meeting diagnostic criteria for GD/GI may later desist from their transgender identity.

In our cohort, 135/1258 (10.7%) had initiated GnRHa treatment at the NCGI. This is much lower than the 63% reported in a Dutch study assessing young people visiting the national gender clinic before the age of 18 years between 1997 and 2018.¹⁵ The lower prevalence might reflect the fact that the Norwegian approach have differed from the Dutch Protocol. Norway might have been more cautious, considering fewer young people to benefit from GnRHa treatment owing to the low evidence of its effect and safety or to the clinical recognition of side effects. Interestingly, the gender ratio was opposite in the Norwegian sample, with a significantly higher prevalence of GnRHa treatment among AMAB (16.9%) compared to significantly more AFAB (53%–77% depending on age) in the Dutch study. There might be a greater clinical focus on biological gain when blocking masculine puberty compared to female puberty in Norway, in addition to the potent masculinisation effect of testosterone.⁴

We found a high continuation rate (95%–97%) of those treated with GnRHa who subsequently started GAHT. This is in line with a Dutch study linking patient data from “The Dutch Cohort” to a nationwide prescription registry with a continuation rate of 98%.¹⁹ The Dutch study concludes that numbers are reassuring in relation to the risk of detransition. However, GnRHa treatment is also hypothesised to be a possible consolidator of gender identity, instead of contributing to open exploration during the critical developmental period of adolescence.³⁴

Among those who were 16 years or older at the end of data collection and therefore potentially eligible for gender-affirming medical treatment, 783/1171 (66.9%) started GAHT at the NCGI. All treatment with GAHT registered in GIRCA was extracted, regardless of treatment initiation age, as long as the primary referral was to the NCGI for children and adolescents. Consequently, our numbers also include those starting treatment after the age of 18 years. Wiepjes and colleagues reported a 32.2% GAHT prevalence among Dutch adolescents who started GAHT without prior GnRHa treatment.¹⁸ Another Dutch study combined GnRHa treatment and GAHT in a probably partly overlapping sample of adolescents, reporting the prevalence of any medical gender-affirming treatment ranging from 53% to 94% depending on treatment year.¹⁷ The high prevalence of GAHT in our Norwegian sample could be due to the inclusion of all registered GAHT regardless of age at initiation. More than half started GAHT after the age of 18 years, underlining the importance of close collaboration with an adult service to ensure consistent follow-up. Significantly more AFAB than AMAB were treated with GAHT in our Norwegian sample. The reason for this is unknown, but it could be related to the natural earlier debut of puberty in AFAB following a more prominent early desire to access medical gender-affirming treatment compared to AMAB. For those who were fifteen years at GAHT initiation, early treatment could be explained by a multidisciplinary team decision to initiate GAHT the year of becoming sixteen.

We found a reduction in the use of GnRHa in recent years. Reduction in treatment could be the result of a more restrained clinical practice in Norway following increased concern regarding the risk/benefit within part of the medical community.^{23, 25} The lower percentage of GAHT reported in the most recent years is more difficult to interpret owing to the different time spans from referral to treatment initiation. A Dutch study also reported fluctuating proportions of GAHT (and GnRHa treatment) over time.¹⁷

Increasing attention is drawn to persons desisting their transgender identity.^9-14 In this study, discontinuation of GAHT was reported and further classified into core or non-core detransition.⁹ In five cases, treatment was stopped owing to an expressed satisfaction with the achieved hormonal effect, and two persons reported a fertility wish. However, the main cause of detransition was the cessation of transgender identity followed by a wish to live in the sex assigned at birth. Importantly, all those registered as detransitioners in GIRCA were AFAB and treated with testosterone from year 2015 or later. This coincides with the sharp increase in referrals to the NCGI.³⁰ The detransition numbers reported in this study are too small to draw any conclusions. However, the gender difference could be due to the higher percentage of AFAB treated with GAHT in our young cohort. Our detransitioning numbers could potentially be the beginning of an increase in persons transitioning back to their birth-assigned gender. Indeed, among AFAB started on GAHT in 2018, one in ten have stopped gender-affirming medical treatment and are followed by the adult gender team supporting them in coping with the irreversible changes resulting from testosterone treatment. It is worth noting that even with close collaboration and a follow-up programme at the adult team, persons discontinuing medical treatment might be lost to follow-up. A recently published Finnish study using national health registers found a 7.9% discontinuation rate of GAHT, underscoring the possibility of our detransition numbers being an underestimate.³⁵

In our study, 11/1258 (0.9%) were deceased by the end of 2023. In a register-based study from Finland, the mortality rate (0.5%) was not significantly different among persons attending gender identity clinics compared to the general population, when controlled for psychiatric treatment history.³⁶ Our Norwegian study could not clarify mortality reasons among the referred. However, the mortality rate emphasises the need for caretaking of the overall health and well-being of persons with GI/GD.

5 CONCLUSION

This study provides valuable insights to gender-affirming care for children and adolescents, owing to its large sample size, including all children and adolescents referred to a national gender clinic over two decades. The study reports varying trajectories, encompassing both medical pathways and assessments ended without gender-affirming medical treatment. Our findings highlight the necessity for long-term follow-up and support of people referred to gender clinics. There is a need for ongoing research on gender-affirming treatment in young people to evaluate the short- and long-term benefits and risks of early treatment interventions, as well as patient-reported outcome measures.

AUTHOR CONTRIBUTIONS

Cecilie Bjertness Nyquist: Conceptualization; writing – original draft; methodology; writing – review and editing; formal analysis. Leila Torgersen: Conceptualization; methodology; writing – review and editing; formal analysis; supervision. Linda W. David: Conceptualization; writing – review and editing; methodology. Trond Haaken Diseth: Conceptualization; writing – review and editing; supervision; methodology. Kjersti Gulbrandsen: Conceptualization; writing – review and editing; methodology. Anne Waehre: Conceptualization; methodology; writing – review and editing; formal analysis; project administration; supervision.

FUNDING INFORMATION

The project was funded by the South-Eastern Norway Regional Health Authority, project number 2021033.

CONFLICT OF INTEREST STATEMENT

Anne Waehre 2020–2022: External referee of “The systematic knowledge overview of gender dysphoria from the Swedish National Board of Health and Welfare's review for medical and social evaluation”. All other authors have no relevant financial or non-financial interests to disclose.

ETHICS STATEMENT

This study was approved by the Data Protection Officer (DPO) at Oslo University Hospital (OUS).