Puberty Blockers Trial

I agree that this needs a longitudinal study design.

I have just seen thread about post-vaginoplasty regret with the belated realisation that the ‘cavity’ doesn’t deliver the orgasmic experience of the previous, functional sex organ.

I have so many questions about the standard of informed consent and how to assess someone’s level of understanding.

https://x.com/hazelappleyard_/status/1896531898442371276?

Totally agree, a 2 year trial is worse than no trial at all. There needs to be 20 year plus follow up, so we can see the impact when these kids start realizing they can't have kids.

Some of your questions wouldn't be addressed ordinarily by an ethics committee. Questions like, is this the right group of people to test this question in would normally be addressed by peer review at the funding stage. RECs won't have the expertise to critique this. They focus on the trial participants and the study team. They will ask to see evidence of risk and benefits to participants, but we know the evidence to date is not compelling either way, largely because the research has been so poor. RECs can and do approve studies in these circumstances. They will have a real challenge in their hands when it comes to informed consent.

I am not so optimistic that gender mania will dissipate. See you here in 2045.

The ethics committee absolutely have to consider the bigger picture. Does this research need to be done? Is this the right group to do it in? Could the question be answered in a different way? Doing research that is unnecessary is unethical - it wastes people's time and public resources. If I was on that REC I would want to see detailed data from people already treated with puberty blockers. If there is sufficient evidence from that group to justify blockers or show they are too unsafe to use the trial is not ethically justified.

I honestly believe that in 20 years we'll be back to where we were in the 1990s - before child gender dysphoria had been invented. I can't see how a 2 year long trial will answer any of the activists' questions adequately. It's pointless.

Trust me, I am not missing this at all. I see huge parallels between this and the clamour for prostate cancer screening. The current tests for Prostate cancer may very well do more harm than good, but activists and some researchers, have been clamouring for a national screening programme.

The activists wanted the screening programme introduced, even with clear evidence it could do more harm than good. There has been lots and lots and lots of research, but nothing of the scale and quality needed to introduce screening on a national level. The national screening committee said no. Finally a proper trial has been funded. This should have been done years ago, lots of time money and effort has been spent on arguments that have not moved the decision any further forward.

Sometimes, particularly when clinical equipoise is in question and when there are activists involved, it is the only way to settle these types of questions. The incremental research just doesn't get you anywhere. It creates conflicting conclusions and the argument just keeps circling back, and the activists get louder each time. I don't want to be having the same discussion in 20 years time

You're missing the incremental nature of this.

Retrospective studies have a lot of faults - but they give us some answers to the long term effects question now rather than waiting 20 or 30 years.

Precocious puberty use shows minimum harm levels. If people taking them for 18 months have X amount of bone loss, people taking them for 5 years are very likely to have have at least that much. If puberty doesn't resume normally when blockers are stopped at 10 or 11, it's reasonable to assume the 'totally reversible pause button' claim is bollocks and it won't resume normally at 17 or 18.

Animal studies give us data on the physical harms - including brain development. What the animal feels about its gender doesn't matter for this side of it.

It's a jigsaw. And the potential for harm is so great that it would be utterly irresponsible to start prospective human trials before gathering the pieces we already have or can easily fill in without using children as test subjects.

As I explained earlier, any retrospective study is likely to generate poor quality evidence.

Precocious puberty is a red Herring. These kids are treated for the minimum period and then go through puberty once the blockers are stopped. They won't tell us anything about kids that take the blockers, go on the cross sex hormones and never go through puberty.

Animals also don't have gender dysphoria and can't express things like happiness and satisfaction. Animal studies may show some of the harms but they will never be able to ask questions about the potential benefits. They just aren't a substitute here. I don't think there is a substitute to doing the trials in people.

If I look at this from a rational pov, I suspect that doing the prospective studies and doing them well will, in the long run, be the best way to keep more kids safe from these unproven treatments.

If I was on the ethics committee being asked to green light one of these studies. I don't think I would, as my job is to look at the study, not the bigger picture...

The majority of the world still believes in trans, gender, and “trans kids”.

Do you think that's true? I don't think it's true at all. I first came across the idea of 'trans kids' only about 10 years ago when I saw the Louis Theroux documentary about Americans transing kids, and I mentally filed it under "Batshit stuff the Americans do", alongside things like child beauty pageants. It was a year or two later when I realised how widespread this was and that it had spread outside America. It's a very new ideology.

I think that lots of (particularly older) people haven't got a clue that there are now child transsexuals.

In 2019 someone who worked in a school told me that there was a girl in the school who wanted to be a boy and the staff were all supposed to pretend that she'd turned into a boy (it was a girls' school). She said that she, along with many other staff, were baffled by this, as they'd never come across the idea of 'trans kids'. This is all very new to many people and I don't think in such a short space of time it would be right to say that most people accept this nonsense ideology.

I'm sure there's more awareness of this now, but I don't think that there has ever been a majority of people believing in children being born in the wrong body.

I think the entire concept of using body modification to treat dysphoria is false and should be abandoned.

A lot of people with bulimia are overweight but we don't treat them with weight loss drugs and surgery.

We shouldn't be jumping to a clinical trial in humans without preliminary work - what does the animal data say? What happens if you block puberty in primates? If that hasn't been done it should be prior to experimenting on human children.

But it's not 'this study now or no study ever'.

As well as the past Tavistock cohort there is the precocious puberty cohort - easier to track, less likely to have skewed dropout problem, plenty of long term info available. And prospective, properly blinded studies can be done on animals.

Proper reviews and crossreferencing of these data would give robust details of harms.

Then we can weigh up whether the known harms might be worth testing against an undefined, unconfirmed, undiagnosable condition that has an 80% recovery rate with watchful.waiting.

Going ahead with human trials at this point means we can't weigh A against B for ethics approval because we don't know A.

So some gay boys are best off castrated?

There are no children who need this treatment. All of these children have normal, healthy bodies. What they need is support with accepting their bodies. There's so little conversation around encouraging adolescents who have distress about their body to focus on the positive things it can do, on feeling positive about having a body that is well and functions as it should.

Agreed it is the very definition of Hobson's choice. I do fear that without some quality studies this debate will rage on for ever. Is it worth risking the health and safety of some kids, (some of whom would go private for this treatment) to answer once and for all whether PBs in kids can ever be justified? How many studies and how many participants would be needed to really answer this question? Will activists just ignore the answer if they don't like it anyway? This will always be a very nuanced debate, with no clear cut right or wrong answer.

Sunlight and data are the antidotes to activism gone wrong. We have thankfully been getting lots of sunlight, but we have precious little data. Without data I get worried that activists will just get smarter at creating arguments. Good data are hard to argue against.

On balance, I think generating the data, even if this means some kids will be harmed, will be the most effective way to minimize harm over the longer term.

I am in a car park on my phone so can't access anything but can we please remember that the guy that did the original 'study' not only ignored his own age limits but is also very high up in the NHS and has OBE type awards for his work?

I can't remember his name, Russell or something.

We know enough @RethinkingLife . We know that they plan to follow these kids for two year - that's right there a 'close the idea down, it won't work' problem. Secondly, we know they do not plan to exclude children with other comorbidities such as ASD, ADHD, eating disorders etc - that's utterly unethical. We also know that the language used is ideological. There is literally no reason to support this trial. it's badly designed. We have 9000 kids to work with already. They had puberty blockers through the NHS. This £10 million should be focused on obtaining the outcomes of these children who are now adults.

While I appreciate the nuance in your points, doesn't it give you a shock to realise that this would negatively impact on yet another group of children? Stopping their brain and body development, effectively sterilising them, rendering them inorgasmic while expecting them to give informed consent to these likely outcomes?

I can't see a way of making this an ethical choice for these individual children.

I completely agree.

The point I was trying to make is that whatever reason TRAs come up with to do the trial they don’t hold water.

And whatever reason TRAs come up with to do the trial ethically don’t hold water either.

I've been involved in obtaining ethical approval for studies and the Research Ethics Committee (REC) absolutely will turn applications down or request amendments - it's very common not to get approval first time, often for minor reasons. Looking online if this was approved I believe the route to object would be complaints to the Health Research Authority (HRA) or funding a legal challenge. Not sure that's ever happened in the UK.

Honestly I think the best parallel here is the US Tuskegee scandal where racist medics left African American men with syphilis untreated to observe the natural history of syphilis in black people. It started in 1932 when treatments were limited (but there were some treatments that worked somewhat) and continued when penicillin was available and they could have been cured very easily. Clinton formally apologised - not that it was during his era, but took decades for the government to apologise.

So the question for Starmer is - will you allow a new Tuskegee to happen on your watch?

But the context is totally different - it is highly challenging to evidence base how we resuscitate people, for obvious reasons. That means that we don't actually have good evidence for using adrenaline - so the baseline is that we don't know if it helps. We also know that most out of hospital resuscitation scenarios are unsuccessful- less than 10% survive. So actually it is justifiable to ask if we are using the right drugs/ techniques, and the level of harm for those in the study isn't high as over 90% die currently.

For gender dysphoria we know that 80% of kids will self resolve after normal puberty. We know that puberty blockers have serious side effects, many of which are irreversible- impact on sex organ development, bone density, voice and so on. Unknown impact on fertility but likely to be bad. So doing a trial has a high risk of harm and low risk of benefit. It's totally unethical in my view and I will gladly contribute to any organisation legally challenging the trial.

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.

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 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.

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.

Chopping your head off might cause loss of head.

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.

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.

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.