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

New “20-year” Study from Amsterdam’s VUmc Youth Gender Clinic: A Critical Analysis

The study’s conclusions and “clinical implications” are not supported by the data presented

SEGM – 2 FEBRUARY 2023

A recent study published in The Journal of Sexual Medicine reported demographic and treatment trends among gender-dysphoric youth seeking evaluation and/or treatment at the Netherlands’ largest pediatric gender clinic in Amsterdam (VUmc) between 1997 and 2018. The study seemingly supports the emerging narrative that “gender-affirming” care for youth has been thoroughly tested over 2 decades; that the long-term trajectories of gender-transitioned youth are both well-understood and positive, as evidenced by virtually no detransition; and that in fact, many “transgender adolescents” do not want any medical interventions—but for those who desire them, puberty blockers, cross-sex hormones and surgery should be widely available, as long as the adolescents are “comprehensively assessed.”

However, a closer examination reveals that these assertions are not supported by the data presented. Below, we briefly explain the design of the study and highlight the study’s main findings. Next, we analyze several key assertions made by the study authors that are not supported by the data. Finally, we discuss the implications of continuing to scale “gender-affirming” medical interventions to the rapidly growing numbers of youth seeking gender reassignment absent reliable research of long-term outcomes.

Brief study description

The study reported demographic and treatment trends in 1,766 patients who were under age 18 when they first presented to Amsterdam’s VUmc pediatric gender identity clinic for evaluation or treatment with puberty blockers. This retrospective study reported the age and sex of referrals to the youth gender clinic between 1997 and 2018 and the rate of uptake of each intervention phase of “gender-affirming” care: puberty blockers, cross-sex-hormones, and surgery. It also reported the conversion rate from puberty blockers to cross-sex hormones.

All trends were analyzed for two distinct groups of patients: those who sought their first evaluations before age 10 and those who presented to the clinic at age 10 or older (defined as “early” vs “late-presenting” groups).

The study’s key findings

Below we enumerate the most relevant points that are well-supported by the study data:

• There was a sharp increase in referrals to the Amsterdam clinic, driven by late-presenting females.The study confirms the epidemiologic trend reported throughout the Western world: a surge in late-presenting cases of gender dysphoric youth, primarily driven by adolescent females. In the Netherlands, this trend began a bit earlier than in the rest of the Western world, circa 2012.Note: as the footnote to the graph indicates, the drop in 2018 observed in Figure 2 (above) does not represent a drop in demand, but rather, redirection of new cases to other clinics in order to keep up with growing demand for services.
• The majority of late-presenting cases were female, while the majority of early-presenting cases were male.The study reported that 67% of late-presenting cases were female (795 out of 1194), compared to only 45% of the early-presenting cases (217 out of 487). (These numbers can be found in Figure 1 in the paper.)
• The majority of late-presenting cases underwent medical transition.The study reported that 77% of the late-presenting “potentially eligible” females started puberty blockers at the Amsterdam clinic (this number was 53% for the late-presenting males). More than 90% of both late-presenting “potentially eligible” males and females started cross-sex hormones at the clinic.
• A significant number of early-presenting cases of both sexes did not transition upon puberty.The data indicate that only 36% of the “potentially eligible” early-presenting males and 53% of the “potentially eligible” early-presenting females pursued medical transition once they became eligible during puberty, while 64% and 47% respectively did not (see Table 2 in the study).The authors also note that “a substantial proportion of children first visiting before age 10 years did not meet criteria for a GD [gender dysphoria] diagnosis.” The extent to which this may be a reflection of the well-established phenomenon of high rates of desistance among those with early-onset gender dysphoria is unclear, as the authors did not specify whether these youth had ever met the criteria for a GD diagnosis.
• Females were much more likely than males to initiate medical transition.More than three-quarters (77%) of late-presenting “potentially eligible” females started puberty blockers at the Amsterdam clinic, compared to slightly more than half (53%) of the late-presenting males. Similar differences between the male and female subjects were observed for the early-presenting cases (53% of females and 36% of males pursued medical transition eventually).The authors note this marked gap between females and males starting puberty blockers: “The difference between AMAB [males] and AFAB [females] in the relative number of people starting GnRHa [puberty blockers] is remarkable.”
• There was a high rate of progression from puberty blockers to cross-sex hormones.The study found a high rate of conversion from puberty blockers to cross-sex hormones—93%-98%. The authors concede that puberty blockers may not serve as a diagnostic tool as previously thought, but rather represent the first step in medical gender transition. The authors also hypothesize that it might be possible that “starting GnRHa in itself makes adolescents more likely to continue medical transition.”
• Surgeries continue to be a core part of the treatment path, but fewer patients are opting to remove gonads (ovaries and testes) since sterilization requirements were lifted in 2014.Following changes in Dutch laws in 2014, which allowed for legal recognition of “sex change” without undergoing sterilization, the number of young people who sought surgery to remove gonads dropped but remained significant. Since 2014, 53% of “potentially eligible” biological males and 38% of “potentially eligible” biological females underwent gonadectomy. A significant proportion of “potentially eligible” females underwent mastectomy (79%). However, mastectomy rates were reported in the aggregate across the entire 20-year span, and the definition of “potential eligibility” for surgery may have inadvertently excluded some youth under 18 who underwent mastectomy in the later years of the study (see point 6, “The reliance on “potential” eligibility” below).

Potentially Misleading Claims

The authors make several claims which, while technically accurate, may inadvertently be misleading. Below we highlight some of these instances and demonstrate the importance and value of reading this paper carefully, rather than accepting its statements at their face value.

1. The study claims to represent “the first 20 years of the Dutch Protocol,” but fails to acknowledge that the Dutch Protocol’s strict eligibility criteria were not consistently followed during the study period.

The Dutch Protocol has become internationally synonymous with the careful and cautious approach the Dutch clinicians devised and documented in 1997, 2006, 2008 and 2012. It required an early childhood onset of gender dysphoria, increase of gender dysphoria after pubertal changes, absence of significant psychiatric comorbidity, and demonstrated knowledge and understanding of the consequences of medical transition. Treatment with puberty blockers could only be initiated at the minimum age of 12. Interventions with clearly irreversible effects—cross-sex hormones and surgery—were not available until ages 16 and 18, respectively. All youth were provided with psychotherapy throughout. The Dutch Protocol specified that youth with “nonbinary” presentations were ineligible for medical interventions, and instead should be treated with psychotherapy.

It is therefore surprising that the authors of the study “redefined” the Dutch Protocol as merely a “diagnostic procedure and combined treatment of GnRHa [puberty blockers] and subsequent GAH [cross-sex hormones]” (p.2) – without ever mentioning the Protocol’s strict eligibility requirements, which have long been juxtaposed to the much more permissive practice of “gender affirmation” which began to proliferate in the West after the publication of the Dutch Protocol’s outcome data in 2014. (The origins of the Dutch Protocol, and the outcomes of the 2014 study which launched the practice of youth gender transitions worldwide, have recently been critically evaluated).

It is even more surprising that the authors refer to the “Dutch Protocol“ and Endocrine Society guidelines by Hembree et al. interchangeably (p. 2). The Endocrine Society guidelines were only issued in 2017, while the study reports on cases assessed and treated between 2006 and 2018. In addition, there are clear differences between the Endocrine Society guidelines and the criteria outlined in the Dutch Protocol in terms of eligibility requirements. Unlike the Dutch Protocol, the Endocrine Society guidelines do not require a childhood onset of gender dysphoria, nor do they set the minimum age for puberty blockers at 12. Instead, the Endocrine Society permits the use of puberty blockers at Tanner Stage 2 of puberty, which can occur in girls as young as ages 8-9.

The authors make several contradictory claims about the fidelity of adherence to the Dutch Protocol’s requirements throughout the 20-year period. They state that the clinic “followed 1 diagnostic and treatment protocol” over 20 years, but also volunteer that “the protocol was adapted” and that “practice has evolved since the start of the Dutch Protocol.” It is unclear when the Amsterdam clinic began to deviate from the strict Dutch Protocol, which was the basis for the seminal 2014 Dutch study. It is clear, however, that as of 2018, the official Somatic (medical) treatment guidelines from the Netherlands no longer adhered to the Dutch Protocol.

According to the 2018 Somatic (medical) treatment guidelines, eligibility for medical transition no longer requires a history of early onset of gender dysphoria—instead, adolescent-onset cases could be medically transitioned. Table 1.2 of the document (auto-translated and reproduced below) indicates that the minimum age at which puberty blockers may be initiated was lowered from age 12 to Tanner stage 2 (which can occur at ages considerably younger than 12), while the eligibility for cross-sex hormones was lowered to age 15 (and the text suggests even younger ages may be considered). The age of eligibility for mastectomy was lowered from 18 to 16. Further, it is unclear whether the DSM-5 diagnosis of “Gender Dysphoria” (with its key element of gender-related distress) is still required to initiate treatment, since the document only refers to the ICD-11 diagnosis of “Gender Incongruence” which has no distress criterion.

While it is expected that clinical practice evolves, it is not appropriate to refer to the “Dutch Protocol” when describing a practice that uses the Protocol’s highly invasive medical and surgical interventions but ignores its clearly articulated eligibility requirements.

The authors state that the goal of the study was to “review how practice has evolved since the start of the Dutch Protocol and to evaluate the treatment trajectories of people who were treated accordingly.” Evaluating the trajectories of youth treated under far less restrictive criteria is critical. However, this question is not answered by the study, since data were not evaluated separately for those treated under the Dutch Protocol and those who were treated under the newer “evolved practice” criteria.

2. The “unprecedented” 20-year time span of the study, listed as the study’s key strength in the abstract, masks a much shorter 4.6-year median patient-level follow up.

While it is technically true that the study data span over 20 years, what this statement fails to address is that in terms of patient-level treatment trajectories, the median follow up is only 4.6 years from the first intake appointment. For 25% of the sample, follow up is less than 3 years from the first intake appointment.

The intake appointment was followed by “comprehensive assessments,” which the authors say are critical, and which presumably took several months to complete. Further, as the study data show, puberty blockers were administered for another 1-2 years. Therefore, a substantial number of youth presenting to the clinic in the later years would have only just started cross-sex hormones around 2017-2018, just as data collection was drawing to a close. Even fewer of them would have undergone surgery by the end of data collection.

To properly evaluate outcomes, follow up consisting of months to a few years after starting medical treatment is insufficient. Prior research suggests that health problems in general, as well as psychological problems and regret often do not peak until a decade later. Recent research from the US, which has been following less restrictive “affirmative care” protocols outlined by the Endocrine Society, reveals that 30% discontinued hormones just 4 years after treatment initiation—a surprisingly high rate, considering that these treatments are intended to be used life-long in order to maintain a feminized or masculinized appearance.

Since the bulk of cases included in this “20-year” study occurred in the last few years of the study, currently available data simply do not extend out far enough to provide reliable information about eventual health outcomes.

3. The study claims that among youth who initiated medical transition, “detransition was very rare”—but the authors never evaluated detransition rates.

The study conclusion states: “detransition was very rare.” This finding has also been elevated into the study abstract, which says: “the risk of retransitioning was very low.” Aside from creating confusion regarding terminology (“detransition” and “retransition” which the authors use interchangeably), these statements may lead readers to the incorrect conclusion that most youth who had embarked on medical treatment stayed on it long term. However, the study never attempted to evaluate the rate of detransition. The only “detransition” rate assessed was detransitioning during the puberty blocker phase. The study did not evaluate detransition rates for youth on cross-sex hormones or those who had undergone surgery.

The authors did find a low rate of detransition during the puberty blocker phase: 93%-98% of youth who started puberty blockers did not discontinue them, and instead proceeded to start cross-sex hormones. This finding led the authors to appropriately conclude that puberty blockers may not serve as a diagnostic tool, but rather represent the first step in medical gender transition—and they even suggest that treatment with puberty blockers may contribute to the high incidence of subsequent treatment with cross-sex hormones….