The Pathways Trial Has Been Paused. But Are We Asking the Right Questions?
A clinical reading of the MHRA letter, what it actually says, and what it leaves out entirely.
Dr Helen Webberley, gender specialist and medical educator
Summary
The UK’s only clinical trial offering puberty blockers to trans young people has been paused. The medicines regulator, the MHRA, wrote a letter raising concerns about things like bone density, fertility, and brain development. The media reported it as a safety scandal. It isn’t.
The concerns in the letter are either well-known effects that are already managed in clinical practice, or they are based on animal studies and a single case report involving one child. The same drug has been given to children as young as two or three years old for a condition called precocious puberty for decades, with far less scrutiny.
Here is what the letter does not mention at all. The evidence that denying care causes harm is enormous. Trans young people who cannot access treatment have nearly double the suicide attempt rate of those who can. Depression, anxiety, and self-harm are significantly higher in young people who are left without support while their bodies go through a puberty they did not want.
The trial was already the only route to care, because puberty blockers are banned outside of it. Now even that route is closed. These children have nowhere to go.
There are already internationally agreed, peer-reviewed clinical guidelines from the Endocrine Society, WPATH, the American Academy of Pediatrics, and Australia, which tell clinicians how to provide this care safely. We do not need a trial. We need to follow the guidelines, provide the care, and collect outcomes data as we go. That is how medicine works everywhere else.
The people missing from this entire conversation are the ones who matter most: the clinicians who actually treat trans young people, the psychologists who support them, and the young people and families themselves. Until they are at the table, we are not having the right conversation.
Deep Dive
On Friday 21st February 2026, the BBC reported1 that the PATHWAYS2 clinical trial, which was designed to assess the impact of puberty suppressing hormones on trans young people in the UK, had been paused. The reason given was safety concerns raised by the Medicines and Healthcare Products Regulatory Agency, the MHRA. By the time most people had read the headline, the conclusion had already been drawn for them.
Dangerous drugs. Vulnerable children. Regulators stepping in to protect them.
I want to ask you to set that framing aside for a moment, because what the MHRA letter actually says is quite different from what the coverage implies. And more importantly, I want to ask a question that nobody seems to be asking at all:
Do we need this trial in the first place, and who should really be deciding that?
What the MHRA letter actually is
The document that has been described as a bombshell is, in clinical terms, a routine regulatory dialogue letter. The MHRA wrote3 to the trial sponsor, King’s College London, to invite a discussion about proposed amendments to the protocol. It is marked confidential. It uses language like ‘we would like to discuss’ and ‘suggested amendment’.
It does not say the trial is unsafe. It does not say puberty suppressing hormones cause harm. It says there are questions it would like answered and areas it would like strengthened before recruitment begins.
That is a normal part of how clinical trials work. What is not normal is a confidential letter appearing on a government website and being reported by the BBC on the same day it was sent. That deserves scrutiny. Who decided to publish it, and why on that particular Friday? These are questions about process and transparency that are worth asking, even if we cannot yet answer them.
The concern about age: why 11 is not too young
The MHRA’s first concern is that the trial includes children as young as 11, and that the minimum age should be raised to 14. Their reasoning centres on the fact that cross-sex hormones cannot be prescribed until age 16, meaning a child who enters the trial at 11 and completes it two years later would still be years away from the next stage of care, and might need to continue on puberty suppressing hormones as a bridging measure.
I understand the logic, but I want to challenge the premise. The purpose of puberty suppression in trans young people is to give them as natural a puberty as possible, just one that is in line with their gender identity rather than their sex assigned at birth. For a child who meets the clinical criteria for gender incongruence under the DSM4 and ICD-115, the window of opportunity to prevent the onset of an unwanted puberty is narrow. Puberty begins when it begins, and for some children that is at 11, or even younger.
We consider delayed puberty in cisgender teenagers to begin at around 14. The same is true for trans teenagers. Their bones, their brains, and their social and emotional development all need a correctly timed puberty. When we talk about the best outcomes for trans young people, we are talking about an experience of adolescence that feels right, that does not leave them permanently marked by physical changes they did not want and did not choose.
Raising the minimum age to 14 does not protect children. It means three years of an unwanted puberty for children who came forward at 11. That is not a neutral clinical decision. It is a decision with profound and lasting consequences for real people.
There is also a comparison that the MHRA letter conspicuously avoids. Triptorelin, the drug used in the PATHWAYS trial, is licensed and routinely prescribed for children with precocious puberty from as young as two or three years old. The MHRA has never raised age-related human rights concerns in that context. The biological mechanism is identical. The only variable is the diagnosis. If the drug is safe enough for a three-year-old with precocious puberty, the age argument alone cannot justify excluding an 11-year-old with gender incongruence.
Bone density: the solution is not to separate, it is to treat as a package
The MHRA’s concern about bone density is the one that comes closest to having a clinical basis, but it is being framed in a way that misrepresents how this actually works in practice. The letter proposes that any child who shows any reduction in bone density at the 12-month scan should be withdrawn from the trial.
Here is what the evidence actually tells us. The reduction in bone density seen during puberty suppression is not caused by the drug itself. It is caused by the absence of sex hormones. This is a well-documented and well-understood effect, and it is exactly the same mechanism we see in people using hormonal contraception that suppresses the menstrual cycle, in people undergoing cancer treatment that switches off their sex hormones, and in people going through menopause. We know this happens. We also know that when hormones are reintroduced in time, bone density recovers.
The clinical solution here is not to withdraw children from a trial at the first sign of a bone density change. The solution is to stop treating puberty suppression and gender-affirming hormones as two entirely separate events, and to treat them as what they are: a single, sequential package of care. You pause puberty when puberty starts. You introduce the right hormones when the person is ready. To stop the blockers and allow an unwanted natural puberty to resume, because a child showed a bone density change that is known and expected and reversible, would cause far greater harm than the change itself.
The proposal to withdraw children from the trial at any sign of bone density reduction is not consistent with how this is managed in any other clinical context involving hormone suppression. It sets a standard for this particular group of young people that does not exist anywhere else in medicine. We should ask why.
Fertility: accurate science, but being weaponised
The MHRA letter raises fertility as a human rights concern, noting that gamete preservation is not possible at Tanner stage 2 because sperm and ova have not yet matured. This is scientifically accurate. It is also being used in a way that does not reflect the full clinical picture.
For a trans girl to store sperm before puberty suppression begins, she would need to go through enough puberty to achieve erection, masturbation, and ejaculation. For many trans girls, that process is profoundly dysphoric. For a trans boy, egg freezing involves a course of strong fertility drugs to stimulate follicle development, followed by a surgical retrieval procedure either through the abdomen or the vagina. These are not simple, painless options that are simply being overlooked. They carry their own significant burden for a young person who is already distressed about their body.
We navigate decisions like this all the time in paediatric medicine. We support families and young people through cancer treatments that carry fertility implications, including in children much younger than those in the PATHWAYS trial. The ethical framework we use is informed consent and best interests, not a refusal to treat because future fertility cannot be guaranteed. The same framework should apply here.
It is also worth noting that trans men who pause testosterone therapy can and do go on to become pregnant. There are published case series documenting this, including people who had been on hormones for many years. The assumption that gender-affirming care means permanent infertility is not supported by the evidence.
What is absent from the MHRA letter entirely is any acknowledgement that untreated gender incongruence also has consequences for a young person’s future, including their future as a parent. A young person who is severely distressed throughout adolescence, who cannot complete their education, who struggles profoundly with their mental health, faces consequences for every aspect of their adult life. That is not weighed in the letter at all.
Cognitive effects: a speculative concern being treated as established fact
The MHRA proposes that adverse fMRI brain scan results should be a withdrawal criterion for the trial, and asks that neurocognition experts define what degree of change would necessitate withdrawal. On the surface this sounds careful and scientific. When you look at what the evidence base actually is, a very different picture emerges.
The primary human study informing this concern is a single case study from 2017, involving one child. The animal studies that support it were conducted in sheep and mice, and the researchers themselves acknowledge that modelling gender identity in rodents is an inherently limited exercise. The most comprehensive review of this question, published in Acta Paediatrica in 2024, examined all available evidence and concluded that no conclusions can be drawn either way about the cognitive effects of puberty suppression in humans. That is not evidence of harm. That is evidence of a gap in knowledge. There is a significant difference between those two things.
There is also no established clinical threshold for what degree of fMRI change would be harmful in a developing brain. Asking neurocognition experts to define that threshold is reasonable in principle, but doing it as a condition of allowing the trial to proceed means we are pausing care for real young people while we wait for experts to answer a question we do not yet know how to ask.
Meanwhile, the evidence of harm from denying care is substantial, consistent, and replicated across multiple countries. A study published in JAMA Network Open6 in 2022 followed 104 trans and non-binary young people over 12 months and found that access to puberty blockers or gender-affirming hormones was associated with 60% lower odds of moderate or severe depression and 73% lower odds of suicidality. Data from the Williams Institute shows that trans people who needed care but did not receive it attempted suicide at nearly double the rate of those who did receive it.
The brain is not unaffected by going through an unwanted puberty. Chronic psychological distress has documented neurological effects. The cortisol load of prolonged anxiety and depression affects brain development in ways that are well established in the trauma literature. None of that appears anywhere in the MHRA letter.
The question nobody is asking: do we need this trial at all?
I want to step back from the specific concerns in the letter and ask a broader question, because I think it is the most important one. The premise of the PATHWAYS trial is that we need randomised controlled trial evidence before puberty suppressing hormones can be offered to trans young people in the UK. But this treatment is not experimental. It is provided according to internationally peer-reviewed clinical guidelines by the Endocrine Society, by WPATH, by the American Academy of Pediatrics, and by the Australian Standards of Care for Trans and Gender Diverse Children and Adolescents. These guidelines exist because clinicians around the world have been providing this care, observing outcomes, and building an evidence base over decades.
The question I would like the MHRA, the government, and everyone involved in this debate to sit with is this: which causes more harm? Waiting for this trial. Having this trial. Or not having this trial, but instead providing care in accordance with established international guidelines and collecting robust outcome data as we go?
Because right now, the young people who needed this trial are not getting care. The ban means they cannot access puberty suppressing hormones outside the trial.
The pause means they cannot access them inside it either. They are waiting. And while they wait, puberty is not.
Who should be at the table
If we are genuinely committed to getting this right, then the conversation needs to include the people who actually know what they are talking about. That means endocrinologists with real prescribing experience of GnRH analogues in young people. It means psychologists and mental health specialists who work with gender-incongruent adolescents every day. It means clinicians who have treated trans young people over time and followed their outcomes. And above all, it means trans young people themselves and their families, because they are the ones living the consequences of every decision that gets made without them.
The MHRA letter reads as though it was written without any of those voices in the room. The concerns it raises are almost entirely framed around hypothetical physical harms, and they are framed in isolation from the psychological and social context of the young people they affect. That is not good medicine. That is not good regulation. And it is not good enough for the children and families who are depending on us to do better.
A note on transparency
The MHRA letter was marked confidential. It appeared on a government website and was reported by the BBC on the same day it was sent to the trial sponsor. I am not suggesting a conspiracy. I am asking a straightforward question about process. Clinical trial oversight works best when it is conducted with integrity, without external pressure, and without the appearance of political timing. The way this has unfolded does not pass that test, and it is reasonable to say so.
If this piece has helped you make sense of a confusing and fast-moving story, please share it with someone who needs to read it. The more people who understand what this letter actually says, and what it leaves out, the better the conversation we can have.
You can find more of my writing and resources at www.helenwebberley.com
Dr Helen Webberley is a gender specialist and medical educator. She is a fierce advocate for trans rights in healthcare and society.
Dr Webberly, I have learned so much from you and I am so grateful you do this work. I am not trans, and I don't have many trans people in my life, but I know from coming out as a lesbian in the 90's how important it is to be believed. I didn't care if the world understood me, I just wanted them to believe me. The hatred for trans people on the Internet sometimes takes my breath away, but the dismissal of someone's reality disguised as care is almost more upsetting. It's "I know what's best for you" because "you aren't what you say you are," and worse, "what you say you are doesn't exist." I'll always remember the first person who believed me. I can imagine what seeing your content would do for a young trans person. Your knowledge and voice is so needed at this time.
I've been waiting for more detailed information on this trial since it was announced. Thank you for this update and the thoughtful way you point out words and actions that raise valid scientific concerns. We need this approach in every scientific endeavor.