Puberty Blockers Trial

[Cismyfatarse]

NHS to launch £10.7 million trial of puberty blockers

www.thetimes.com/article/1a43ff7e-3929-4d78-9ac4-7490b5cc2e2e?shareToken=14e04db1b508819178c480124574cb9b

I really, really hope they are not going ahead with this. I have only skim read the article. But can you trial something where there is evidence of harm?

In a randomised controlled trial, participants are put randomly in a particular treatment group.

In a blind RCT, the participants aren’t aware of which group they’re in.

In a double blind RCT neither participants nor the observers of outcomes know which group they’re in.

Obviously with puberty blockers the latter two aren’t possible. But a RCT is possible.

There are issues to overcome (aside from the ethics of sterilising children etc):

It has to be properly random. The treating team can’t say “well this kid is more ‘insistent and persistent’ in their gender identity, they’re better off in the PBs arm.” No. It has to be completely random.

The outcomes can’t be pre-conceived. This is a massive problem. Both gender clinicians and parents/kids as two groups have the pre-conceived idea that PBs are the “right” choice already. A research clinician has to be willing to accept, and tell the participants, that there is an equal chance of all possible outcomes permutations:

Better with PBs vs therapy
Better with therapy vs PBs
No difference
Worse with PBs vs therapy
Worse with therapy vs PBs

The participant has to be consented to all possible outcomes and be willing to accept that. Any parent who says “I know my kid will be better on PBs so if she doesn’t get that, there’s no point” should be excluded.

This is what makes such a trial so difficult. Zealots have put the cart before the horse so intensely that there is a high risk of bias if they’re involved in any way. It needs to be set up and run by a non-gender clinic, and patients selected very carefully.

This is what makes such a trial so difficult. Zealots have put the cart before the horse so intensely that there is a high risk of bias if they’re involved in any way. It needs to be set up and run by a non-gender clinic, and patients selected very carefully.

But informed consent is impossible, so surely that makes it a non-starter.

This trial is completely unethical. It should stopped. While I’m glad to see Our Duty come out so strong and Marcus Evans, I’m disappointed that other organisations seem pretty muted. We should be up in arms

Genspect have published a detailed criticism of puberty blockers and their unethical experimental use on children:

https://genspect.org/wp-content/uploads/2025/03/Genspect-UK-Briefing.pdf

Everything makes it a non-starter.

The lack of a clear disorder and treatment group.

The unethical nature of the treatment.

The problem with consent.

The bias of pre-conceived outcomes.

The limitations of the timeframe.

It has nothing going for it.

Totally agree, so many problems.

But Dr Cass said there should be a study. She's said many things we agree with, she's tried to wrest data on the patients who've already been through this regime, and she said there should be studies. And she's far more expert than me.

What did she envisage? Is it being set up the way she would have hoped? (Two years? Surely not. The report says "with follow-up into adulthood")

It's hard to see how an ethics committee is going to be able to consistently say no to this thing, given such an eminent authority as the Cass report recommending it. And given that like most public services, if they send it back enough times it will eventually land on the desk of a true believer.

I hope I'm wrong. I think it will go ahead because of politics and I'm worried about what it will say, after only two years, with all the bias in the patient group. And, I have to assume in the medical group too, as I can't see how a GC or neutral medic could get round all the ethical issues to want to work on this.

I had wondered this too.

I don't know how ethics committees for clinical trials work so maybe someone who does can weigh in on how likely this scenario is. If the trial in its current form doesn't get past the ethics committee can the researchers make changes to their proposal and resubmit?

A small (and probably irrational and wishful thinking) part of my brain is hoping that the ethical practitioners are playing a long game in proposing a trial in this way in the hope that it shows exactly how unethical and impossible it is and an ethics committee could not approve it, and so the trial approval process would go back and forth interminably trying to make the impossible possible and the unethical ethical, with the result that this particular can would be kicked down the road until the influence of gender zealots in public institutions has waned.

Of course this strategy and scenario would be extremely convoluted really quite bonkers but this is what gender does - nothing makes sense and nobody can speak the truth on pain of cancellation/ostracisation so we end up with all sorts of convoluted situations and double speak.

Also, the gender zealots letting go of their iron grip on public services is probably wishful thinking as well on my part, because the nature of zealous belief systems is that people don't let go of them readily.

To add to the unfortunate likelihood of this trial going ahead, Prof Gordon Guyatt, one of the pioneers in evidence-based medicine is in favour of it, as per this BBC article from December: https://www.bbc.com/news/articles/clyd2qe5kkjo

From the BBC article:
Gordon Guyatt, a professor at McMaster University in Canada, who points out that randomised trials are done in "life-threatening stuff all the time" where no-one can be sure of the long-term effects of a treatment. In his view it would be "unethical not to do it".
"With only low quality evidence, people's philosophies, their attitudes or their politics, will continue to dominate the discussion," he argues. "If we do not generate better evidence, the destructive, polarised debate will continue."

I find it a bit astonishing that people are willing to harm children to get better evidence, especially since Guyatt was the lead researcher (I think) for some recent research from McMaster university which I believe came to the same/similar conclusions as Cass. I haven't read the McMaster research so open to any corrections there!

I feel like I tied my brain in knots thinking through the above scenario! And that I'm not making sense to myself anymore. Gender nonsense is crazy making for me :(

"Randomised trials are done in "life-threatening stuff all the time""

An interesting take from the doctor given that gender dysphoria isn't a life-threatening condition...

Gordon Guyatt is considered the world leader/guru on Evidence-Based Medicine. His systematic review into puberty blockers was published in January. Of course it showed no evidence of benefit.

https://adc.bmj.com/content/early/2025/01/29/archdischild-2024-327909

The best example of how RCTs are done on life threatening circumstances is the study done a few years ago in which paramedics were blinded to whether they were randomly giving adrenaline or saline as part of cardiac arrest resuscitation. It was thought that adrenaline might actually be making things worse. The study showed slightly better survival but more brain issues:

https://www.bbc.com/news/health-44859777.amp

So if people who are actually actively dying can be subject to a RCT, kids who don’t want their breasts to grow or their voice to change certainly can.

Gordon Guyatt is considered the world leader/guru on Evidence-Based Medicine. His systematic review into puberty blockers was published in January. Of course it showed no evidence of benefit.

The conclusion of that paper seems to be "we are very uncertain about the effects of this treatment ".

There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention.

But I would dispute the conclusion that further studies are needed without a clear and unambiguous definition of what the condition is and why cosmetically altering the bodies of adolescents with drugs that will impact their sexual function and fertility as adults is an appropriate treatment for whatever this condition turns out to be.

This is a mental health condition with symptoms like depression. Why would anyone think that a physical treatment which results in infertility and impaired sexual function will lead to these patients having better and happier lives as adults? It seems extremely unlikely to be the case.

@NotBadConsidering
Thank you for that, I guess my hair-trigger went off too quickly regarding the intent of a talking-head...

But I suppose my concern remains in two ways - I appreciate that we do undertake RCTs on life-threatening illnesses, but by talking about PBs in this way I feel as though it gives credibility to the idea that gender dysphoria is actually a life-threatening illness inherently. Will the risk to the patients be commensurate if there isn't an underlying threat to life that is to be treated?

With the saline example, there are well-understood mechanisms of the illness being treated, with measurable outcomes for a specific treatment. I fear that gender dysphoria as a diagnosis lacks rigour - what makes it different from other anxiety disorders, body dysmorphia, BID?

So the biases created by the presumptions of i) that there is even a distict diagnosis to be had, and ii) that the illness is life-threatening skew the basis of the trial.

There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention

Agreed. I doubt Guyatt would consider the NHS study to be methodologically rigorous. It’s just a further unhelpful study that will score indifferently for GRADE, RoB etc.

Getting this through ethics will be interesting. Their starting point will be whether there is clinical equipoise - that there is genuine uncertainty over what treatment is best. If the committee finds that is it obvious that PBs are likely to be less effective/more harmful than the control arm, whatever that might be, then the trial cannot go ahead.

I can imagine this will not be unanimous in the committee. Committees are drawn from across society. They have lay members and professionals and they consider all types of trials, from cancer to depression. It would be very hard to nobble a committee.

They might have a sense for which committee would be likely to be more sympathetic to his study or they might try and stack the membership in advance of the trial being reviewed, but otherwise the committees are genuinely independent.

To hope they publish the comments from the committee

I don’t understand how people give Gordon Guyatt credibility. SEGM made a big deal about having him at their conference and writing papers with him and then, after all that, he said it would be “unethical” NOT to have a trial: https://www.bbc.com/news/articles/clyd2qe5kkjo.amp
Having said that, SEGM are as bad as Guyatt, they don’t seem to understand why a trial is fundamentally unethical x.com/segm_ebm/status/1895125127714492834?s=46

To hope they publish the comments from the committee

I don't know what is normally published about the comments made by ethics committees, but this contains some from the original Tavistock study.

https://www.hra.nhs.uk/about-us/governance/feedback-raising-concerns/investigation-study-early-pubertal-suppression-carefully-selected-group-adolescents-gender-identity-disorders/

So is the big gamble here that it won’t get through the ethics committee and then the comments will save the day for everyone? Helluva risk imo

Placemarking.

The Our Duty piece expresses clearly my position that the 'medical problem' to be treated is actually a harmful ideology . And I agree with PPs that gender incongruence is yet to be defined satisfactorily.

My family had a very light brush with PBs (for suspected precocious puberty, nothing to do with GI) and the endocrinologist was crystal clear - PBs are extremely powerful drugs which would only be administered in extreme cases for a short a time as possible. She was very keen for the parents to understand the awfulness of the possible consequences.

My family member went in convinced it would be the best thing for her (very young) child but came out convinced that they'd never agree to their use.

To me, Guyatt's comments in combination with that study suggest that he may be an honest researcher (he's not cherry picked results or refused to publish when the study gave the 'wrong' result) but he is a believer in the condition. And therefore wants to keep trying to find a cure. Which means more trials to find a combination of factors that will give the 'right' result.

(By which I don't mean to suggest that he wants to fake a trial, but that he does believe blockers can work if given in the right dose, at the right time, for the right duration, and to the right cohort - and that harmful experiments are justified to combat the 'greater harm' of not finding that combination, and therefore having a treatment for a condition that he does think is life threatening. He's not taken the further step of thinking 'Hang on, do we.need a trial to determine the condition exists/actually is that serious? And of so, is this specific body modification of children a logical approach to treatment?')

One can be a guru in a method, but still make errors in applying it.

In the SEGM thread they comment that we still don’t know anything about the actual trial design or protocol from the NIHR information.

When a commenter remarks that they don’t see how it might succeed in gaining ethics approval, SEGM concurs and describes it as “challenging “.

On the face of it, I would agree with both of these. I am not sufficiently familiar with SEGM’s broader views to comment on those.

Chopping your head off might cause loss of head.

That is the nub, there is so much uncertainty here, and research can be really helpful in gaining clarity. But, you have to know what are the best questions to ask, and what a good outcome looks like.

I suspect there may be a small cohort of kids, likely gay boys with entrenched and internalized homophobia, and/or rejection of toxic masculinity that, by the time they are teens, may have better quality of life if supported to transition. The question for me then becomes how do we spot these kids early and help them to be more comfortable in their bodies.

One of the things that makes this research hard is the skewed thinking about outcomes. In some camps transitioning isn't about achieving better outcomes, it is about reducing feelings of dysphoria and realizing your true inner self, even if that makes you miserable, infertile, obese and anorgasmic.

We need to go back to first principles of interventional medicine. Do no harm. Intervene as little as possible.

We have to start from the position that medical transition is an option of last resort.l, not something to be celebrated on socials.

I don’t think Guyatt is unique in believing there’s a condition that needs attention and evidence for its treatments. This forum is the only place where people really stop and think - and are prompted to stop and think - about what is actually being treated. The majority of the world still believes in trans, gender, and “trans kids”. Making everyone else stop and think is the next big step, and part of the ethics board review should be about considering the condition being treated.

This is absolutely what we need to be shouting for! There are already hundreds of people who have been given puberty blockers in the UK - why aren't their outcomes being reported? Even when their Drs were too sh*t to follow them up they could still do anonymised case note reviews. It's maddening.

I am not convinced a retrospective study will move the debate on. A retrospective study, with data collected outside of a trial setting will never be as robust as a prospective study. And by follow up, what do we mean? Access NHS records of those treated at the Tavi and see how they are doing medically? That would at best give half a picture.

Follow up would likely need to involve speaking to those who were treated and asking more questions about how they are doing in life. Finding these people and getting consent will be really difficult and open to bias. Eg. Those who are easy to find may have had more stable lives, those lost perhaps more chaotic.

The Cass review pointed out that the quality of research in this field is poor. I am not convinced that a quality retrospective study can be done. More poor research won't solve anything.

We either say outright that medical transition in children will never be sanctioned. Or we do the research. The former position I worry will be vulnerable to political winds. The latter at least builds the evidence base for safe and effective medical practice.