Puberty Blockers: Can A Drug Trial Resolve This Controversy?

Unfortunately, though, when I visit there’s always the risk that something goes haywire and I end up needing an operation if that occurs! So there you are; my three top picks for best places in London to watch films about people doing stupid stuff with money they shouldn’t. Getty Images/Shutterstock It remains one of the most critical challenges in contemporary medicine – how to identify whether the benefits of puberty blockers (drugs that delay puberty) outweigh potential harms. This issue came to a head when NHS England proposed in June 2023 that these drugs only be prescribed to children questioning their gender as part of clinical research studies in future. Since then, however, a new government has come into power at Westminster with Health Secretary Wes Streeting declaring his support in setting up “clinical trials” that establish evidence. The National Institute for Health and Care Research is expected to confirm funding is in place for a trial soon, yet how should such an event unfold remains an open question – 18 months since announcement there remains little agreement as to how such a trial should proceed. Around this same time, approaches that had traditionally consisted of providing psychological and social support began referring clients directly to services offering hormone medications – specifically puberty blockers known as gonadotropin-releasing hormone (GnRH) analogues – such as gonadotropin-releasing hormone receptor analogues or “puberty blockers.” Puberty blockers work directly on the brain in order to halt any surges of estrogen or testosterone associated with puberty. Years ago, they were frequently prescribed to young patients suffering from gender dysphoria – those who believe their gender identity differs from that of their biological sex). However, in March 2024 NHS England discontinued routine prescribing of puberty blockers to individuals under 18 as part of an overhaul to children’s gender identity services. NHS England stated in their policy statement: ‘Currently there is not enough evidence supporting either safety or clinical effectiveness of PSH [puberty suppressing hormones] treatments routinely available.” Scotland paused their use, while Finland, Sweden, France, Norway and Denmark reviewed their positions regarding medical interventions aimed at those aged under 18 – such as puberty blockers – to various degrees. There is still support for puberty blockers. Medical ethics experts may believe there should be an obligation for ethical consideration of treatments where there remains genuine uncertainty as to their relative benefits and harms; some consider equipoise as such treatments require further scientific evaluation in order for ethical decision makers. But not everyone agrees on an equitable solution in this instance, the BBC has learned about ongoing debate surrounding trial proceedings and what could happen during them. Some argue that since there is already evidence supporting puberty blockers’ beneficial properties for mental health, any trial would be unethical as it might mean some young people experiencing gender distress may go without treatment; as a result of which WPATH have expressed serious reservations over its conduct. They advocate for using puberty blockers, cross-sex hormones and surgery as treatments to delay puberty. WPATH guidelines have recently come under increasing criticism by clinicians, with some alleging it to be unethically problematic if participation in trials becomes the only option to access care that has proven itself as medically necessary and lifesaving. “Other clinicians believe there is no solid evidence showing puberty blockers can aid with mental health at all. Research questions the detrimental effect that medicines might have on brain development among teenagers as well as evidence illustrating bone density loss. Dr Louise Irvine is a general practitioner (GP) and co-chair of the Clinical Advisory Network on Sex and Gender which advises caution regarding using medical pathways when treating gender dysphoric children. She notes: “Given that puberty blockers alter an integral aspect of human development, their benefits must be tangible and significant to justify any risks to children. “With regard to advancing a puberty blockers trial, we are concerned that political considerations are taking precedence over clinical, ethical and scientific concerns as well as children’s health and wellbeing.” “NHS Adult Gender Services holds data for more than 9,000 young people from their youth service.” Some have advocated that any trial should first undergo careful consideration as this could provide important insights into potential risks posed by taking puberty blockers. On the other hand, others such as professor Gordon Guyatt from McMaster University in Canada hold another perspective, noting that randomised trials are regularly undertaken on “life-threatening stuff”, with no guarantees over future effects from treatments being administered in randomised fashion. According to him, failing to produce high quality evidence would be unethical and cause further debate in which people’s individual philosophies, attitudes or politics will continue to impose themselves onto public debate without adequate solutions or evidence being generated in response. He states: If more solid data cannot be produced soon then destructive and polarised arguments will persist.” Dr Cass argued that existing research in his field was of low-quality, providing insufficient information upon which clinical decisions could be based. Study participants enrolled in many existing studies may also receive psychological support and medical treatment; it was therefore sometimes impossible to disentangle their effects separately.- Dr Cass remarked, when it comes to suppressing puberty with drugs “its rationale remains unknown”. One of the primary motivations given for taking puberty blockers was to give oneself more time for contemplation by delaying puberty’s arrival; however, evidence indicates that most individuals taking such medications eventually end up taking cross-sex hormones such as estrogen or testosterone for cross-sexual stimulation. Cass’ report suggests one theory for why puberty blockers might alter gender identity development: Clinicians “cannot predict with any certainty” which young people “will go on to develop an enduring trans identity”, wrote Dr Cass. There is still little clarity surrounding which young people might gain from participating and which may suffer overall from the process. Recruitment for the trial has yet to start; its scheduled commencement was initially set for 2025 but now expected sometime sooner. Young people will typically be referred for assessment by specialist clinicians. There remains much to determine, such as how many participants there will be for these trials and whether people who receive intervention fare better than those who don’t. Scientists overseeing them must subsequently ascertain if those receiving an intervention fare any better than those who don’t receive one. Does puberty blocking drugs improve young peoples lives and mental wellbeing? “Better off” refers to any improvement that occurs with regards to satisfaction with one’s physical appearance and confidence levels. Quality of life can be determined by various factors such as self-confidence and self-esteem. As well as collecting personal opinions of young people and parents, a trial could measure real world changes such as time spent studying or with family and friends; also taking into consideration potential harms such as reduced bone density. Some scientists propose testing its impact on learning using an intelligence test (IQ test). Normal brain development is determined by both puberty and chronological age interacting during adolescence; it remains to be seen how suppressing puberty might alter this relationship. Brain scans provide one way of understanding any effect. Some scientists think it may be feasible to randomly assign trial participants into two groups where one gets puberty blockers while the other gets placebos without anyone knowing which group they belong in; but others argue a placebo group cannot exist. Researchers predict that children in the placebo group would go through puberty, discover they weren’t on puberty blockers and realize they weren’t receiving medical care or treatments as part of this trial, leading them to either drop out altogether or seek other avenues to procure these blockers. Either scenario would erode the validity of results. Professor Gordon Guyatt and others have proposed conducting a trial where children who want to transition socially (such as by altering how they dress or changing names and pronouns ) make up an entirely non-drug group in this trial. Researchers could then measure differences amongst trial groups. An alternate possibility would be for both groups to receive puberty blockers but one group receives them later, in conjunction with receiving psychological and emotional support during that interim period. Researchers could then use this to gauge if their gender-related distress lessened during that delay while receiving support. There would also be a “matched” control group consisting of those not taking placebos or puberty blockers – whether due to health reasons or because they choose not to – but who have similar tests and scans conducted. Getty Images The Gender and Identity Development Service (GIDS), founded at London’s Tavistock Clinic in 1989, serves to support young adults as they go through puberty stages when various physical changes take place over time. Getty Images Thirdly, researchers may want to experiment by giving puberty blockers at different points during puberty in two separate groups – this would enable them to understand when is best time. As an example, this would enable researchers to observe whether early use of medication helps enhance wellbeing by decreasing gender-specific body changes. They would also be able to determine whether starting drugs earlier has more detrimental impacts on bone density and brain development, especially given children referred to GIDS typically experience increased rates of anxiety, depression, eating disorders and autism compared with general child populations. Trial participants would still receive treatment related to these conditions; however, any differences in results between groups due to different drugs must be adjusted to account for all these considerations and ensure reliable and definitive data in this field is collected.What parents saySeveral parents are closely watching this experiment play out. Annabel (not her real name) is part of the Bayswater Group – an informal network of parents whose children questioning gender who oppose medical interventions to treat gender dysphoria. She initially considered taking puberty blockers when her own daughter began questioning her gender in early adolescence; an option presented by GIDS; ultimately her daughter decided against them. Annabel had reservations regarding their effectiveness; she wasn’t convinced there was enough proof, nor knew what effect the trial would have on her daughter’s physical and psychological well-being in the long term. To this day she still has some unanswered questions relating to it all – as well as additional ones regarding its trial process itself. “One of my main worries with regard to this new trial if approved is whether we will gain evidence we need? Or will more weak data, as indicated by Dr Cass, undermine decision-making? Natacha Kennedy of Goldsmiths University London who conducts transgender-related research recently conducted an in-depth survey among parents of young people experiencing gender-related distress post puberty blocker ban. The results are presented here for their consideration.” She believes that puberty blockers should be available as an option to young people questioning their gender identity, since many will refuse being part of a placebo trial group. “These parents are in desperation; if [they] attend a trial only to learn that their child won’t actually receive puberty blockers, there would be little point,” according to Salinas. Some may seek alternative means in order to access these drugs for themselves and find another means. “No matter the trial format chosen, increased scrutiny will follow. Debate will rage about the trial’s merits and what its results tell us, with scientists from around the globe closely watching what unfolds here in Britain. Unfortunately, though, more time may need to pass before fully comprehending its long-term impacts on physical and mental health of those taking puberty blockers compared with those with gender-related distress who don’t take them. No one knows for certain exactly how many individuals detransition, though according to Annabel it appears numbers may be increasing as evidenced in the Cass report. “Long term follow up is essential,” according to Annabel. Can children comprehend what that signifies for their future lives and fertility? Now, Deborah Cohen along with many parents, carers and young people must await the verdict from this trial in order to know whether puberty blockers will once more be prescribed to children in future.” Deborah Cohen used to cover health for BBC Newsnight before becoming a Visiting Senior Fellow at LSE Health; Top image via Getty. BBC InDepth provides access to our top journalists’ analysis and expertise through online and mobile channels. Under our distinctive new brand, we will bring you new perspectives that challenge assumptions, in-depth reporting on key issues to help make sense of an increasingly complicated world, thought-provoking content from BBC Sounds and iPlayer and much more! We are starting small but thinking big and would love your input; please click below for feedback submission!