Unlike Europe, where national health service (NHS) agencies regulate the practice of medicine, the decentralized nature of the US healthcare system presents a distinct challenge when it comes to healthcare regulation. This is especially evident in the case of youth gender medicine, which relies on "off-label" prescribing. This practice allows doctors to prescribe a drug that has never been tested for the current indication, provided that it has been FDA-approved for another indication and the physician believes that such off-label use can benefit the patient.

Although the original FDA approval for both puberty blockers and sex hormones dealt with distinctly different clinical uses and markedly different populations than the current use of these drugs for gender dysphoria, there is no apparent mechanism by which any federal U.S. healthcare regulatory agency can now step in to regulate the use of these interventions for gender dysphoria in youth—even as the evidence of the unfavorable risk-benefit ratio continues to mount. This leaves the practice in the hands of gender clinicians themselves, who often have substantial financial, intellectual, and personal conflicts of interest.

This regulatory vacuum has enabled several US states' legislatures to step in with bans or restrictions on the use of puberty blockers and cross-sex hormones for dysphoric youth. To date, 26 states have passed such laws, evoking the long-standing US constitutional tradition which allows states to safeguard its citizens from "unprofessional, improper and incompetent practice of medicine." Multiple lawsuits have subsequently been filed by transgender advocacy groups against the states, asserting that such laws are discriminatory. 

As an inadvertent result of this development, the U.S. courtrooms have become the main arena for debating scientific evidence for puberty blockers, cross-sex hormones, and surgery as treatments for youth gender dysphoria—and court disclosures have become a valuable source of evidence not available elsewhere.

One such example is a recent submission of an English translation of Sweden's official 2022 national practice guideline for children and adolescents with gender dysphoria.  In February 2022 Socialstyrelsen (Sweden's National Board of Health and Welfare) updated the hormone section of their treatment guidelines, as reported in a SEGM Spotlight from the time. By December 2022, however, Sweden had fully updated its official treatment recommendations (Vård av barn och ungdomar med könsdysfori), but only a summary of this 111-page document was officially made available in English. The summary provided highlighted of the most salient points, such as the conclusion that, for most affected youth, the risks of the medical and surgical interventions outweigh any benefit:

"At group level (i.e. for the group of adolescents with gender dysphoria, as a whole), the National Board of Health and Welfare currently assesses that the risks of puberty blockers and gender-affirming treatment are likely to outweigh the expected benefits of these treatments. The National Board of Health and Welfare therefore gives the following weak, negative recommendations as guidance to the healthcare system:

• Treatment with GnRH analogues, gender-affirming hormones, and mastectomy can be administered in exceptional cases."

While no official translation of the entire document exists, a certified translation of Sweden's 2022 guidelines for gender dysphoric youth was recently submitted into evidence in a landmark US court case over the practice of youth transitions. It makes further details on several key recommendations more accessible to non-Swedish-language speakers. The full guidelines (also available as an attachment to this spotlight) include 18 recommendations on a wide range of issues related to youth gender medicine.

Below is a subset of key recommendations:

Psychosocial Evaluation and Support

• Comprehensive evaluation: Carry out the psychological, psychosocial, and psychiatric components of gender incongruence evaluation using valid assessment methods, investigative interviews, and life histories obtained from the child or adolescent and from the guardians. (p. 63)
• Exploration of gender identity: Provide psychosocial support for the unconditional exploration of gender identity during the evaluation of gender incongruence in children and adolescents.  (p. 66)
• Screening for ASD/ADHD: Prior to or at an early stage of gender incongruence evaluation, systematically screen all children and adolescents for signs of ASD and ADHD. In cases where there are signs of ASD, neuropsychiatric assessment should be initiated. (p. 69)
• Treatment of co-occuring psychiatric conditions: Systematically identify and assess any potential concurrent psychiatric conditions before or at an early stage of the evaluation of gender incongruence in all children and adolescents. Offer psychosocial support and psychiatric treatment to reduce potential poor mental health throughout the course of the evaluation of gender incongruence in children and adolescents. (p. 71)

Medical and Surgical Interventions

• Puberty blockers: Treatment with GnRH analogues for adolescents with gender dysphoria should be provided in the context of research. Until a research study with ethics board approved inclusion and treatment criteria is in place, it is the National Board of Health and Welfare's assessment that treatment with GnRH analogue may be given in exceptional cases, in accordance with the updated criteria in the medical guidelines. (p. 85)
• Cross-sex hormones: Gender-affirming hormone treatment with testosterone or estrogen for adolescents with gender dysphoria should be provided in the context of research. Until a research study with ethics board approved inclusion and treatment criteria is in place, it is the National Board of Health and Welfare's assessment that gender-affirming hormone therapy can be given in exceptional cases, in accordance with the updated criteria in the guidelines. (p. 90)
• Surgery: Mastectomy for adolescents with gender dysphoria should be carried out within the framework of research. Until a research study with ethically tested inclusion and treatment criteria is established, the National Board of Health and Welfare's assessment is that mastectomy can be offered in exceptional cases, for adolescents who meet the updated guidelines criteria for gender affirming hormone treatment. (p. 95)

Helpfully, the translation provides additional notes (pp. 126–128) that explain the context for some of Sweden's recommendations. For example, it explains that Sweden's decentralized healthcare system comprises 21 regions, with Socialstyrelsen establishing national guidelines and policies to ensure equitable healthcare provision based on the best available knowledge. The notes also highlight a conundrum facing the Swedish healthcare system related to its transition to WHO’s ICD-11 "gender incongruence" codes. Previously, Sweden had used the unspecified ICD-10 code F64.9 as a provisional diagnosis for gender dysphoria, pending a differential diagnosis to determine if other factors, such as mental health struggles, explained the individual's experience of a mismatch between gender identity and recorded sex. Only patients for whom no other explanation for the symptoms was found would receive the "final" diagnosis of F64.0 for individuals with a cross-sex identity, or F64.8 for those with a non-binary identity. 

However, the report notes that under the ICD-11 system, there are no codes that would allow for the provisional diagnosis (p. 22). Once an individual presents with gender incongruent feelings, the presumption is that the diagnosis is final. This complicates proper coding during the assessment process and represents a deviation from how Sweden historically handled the coding of provisional vs final gender dysphoria diagnoses.

The English translation of Sweden's guidelines helps bring wider attention to a pattern emerging across Europe: when national healthcare regulatory bodies conduct a systematic review of evidence, they consistently conclude that the evidence base for medical gender reassignment in children and adolescents is of insufficient quality to justify continued use of this practice in regular medical settings. Instead, as typical with experimental treatments, youth gender transitions are increasingly restricted to research-only settings with tight eligibility criteria and extensive oversight to minimize harms to individual patients, while generating knowledge that can benefit future patients. 

SEGM take-away

In 2020, Finland's treatment guidelines were the first to explicitly state that hormonal gender transition for youth is experimental. The guidelines concluded that "in light of available evidence, gender reassignment of minors is an experimental ['kokeellisia'] practice." In 2022, we can see that Sweden reached an even starker conclusion, stating that "the risks of puberty blockers and gender-affirming treatment are likely to outweigh the expected benefits of these treatments" and limited such treatments to research settings, allowing for exceptions pending the setup and ethics approval of a research trial.

In 2024, the Cass Review decommissioned the use of puberty blockers from general medical practice, and recommended that "a full programme of research be established." NHS England's three-year implementation plan further clarified that this recommendation applies to all endocrine interventions (not just puberty blockers), emphasizing that the benefits of these interventions are unproven, and that the aim of the research program is to provide better evidence for future generations:

"We don’t know enough about who might benefit from medical interventions as part of their package of care, but if the clinical team think that this may be the right pathway for an individual, they will have access to those treatments as part of a carefully constructed research programme; this approach will give a better evidence base for future generations of young people."

Where does that leave the current state of gender medicine in the US? The FDA's statement on clinical research vs. medical treatment provides a helpful starting point (their table is replicated below; our highlighting). It suggests that when there is uncertainty about the benefits of any given treatment, and the intended benefit is to inform the care of future patients, the intervention is classified as clinical research. Thus, applying the framing of Finland, Sweden, and most recently, England, and following FDA guidance, treatments involving puberty blockers, cross-sex hormones, and surgery appear to belong in the category of "clinical research" rather than "medical treatment."

The National Institutes of Health grant-funded research proposals provide further evidence that these interventions are experimental, with unknown risks and benefits. Consider for example the proposals from four research projects dating from either 2023 or 2024, that together have been awarded over a quarter of a million dollars in funding:

“Little is known about how pubertal blockade, the first step in the medical management of a young transgender adolescent, affects bone health and psychological well-being.” Skeletal Health and Bone Marrow Composition Among Youth: 5R01HD101421-05.

“GnRHa [puberty blockers] may ... disrupt puberty-signaled neural maturation in ways that can undermine mental health gains over time and impact quality of life in other ways. The overall impacts of GnRHa treatment have not been systematically studied.” The Impact of Pubertal Suppression on Adolescent Neural and Mental Health Trajectories: 5R01MH123746-03.

“GAHT [gender-affirming hormone therapy], particularly estrogen, may increase the risk of thrombosis … the objectives of this proposal are to prospectively examine biologic changes associated with thrombotic risk in a cohort of transgender youth receiving estrogen." Thrombosis Risk in Transgender Adolescents and Young Adults Starting Gender-Affirming Hormone Therapy 5R01HL161153-02.

“The relatively recent introduction of cross-sex hormone therapy for transgender youth represents a significant shift in clinical practices, however underlying mechanisms for these interventions are poorly understood, particularly during early stages of puberty." Sex Hormone Effects on Neurodevelopment: Controlled Puberty in Transgender Adolescents: 5R01MH115349-05.

The recognition that endocrine and surgical interventions for gender dysphoria are still in the clinical research phase and have not reached the threshold of "medical treatment" should have a profound impact on how such services are delivered and regulated in the United States. This issue, among many others, will become key to the ongoing US debates of whether and how the field of youth gender medicine should be regulated.