Puberty Blockers clinical trial.

[PlainJane999]

Simple question, do those here support the prescription of blockers as part of a clinical trial and why?

Cass does recommend a similar approach to what you are suggesting but rather then banning blockers doing that form of study simultaneously.

The ethics of using patient data without consent is a different topic which could have it's own thread.

I can't remember who was involved but there was a big campaign by TRA's to get former GIDS patients to withdraw consent/not provide consent for their patient data to be made available to the Cass review (Stephen whittle was one of the instigators)

I cannot see how a trial could be designed so that it is ethical. If someone cleverer can design such a trial, I would change my mind.

Patient welfare isn’t ‘improved’ if the blockers cause life long physical problems but that seems to be more of an issue for the born-female kids than the born-male kids and you never seem very interested in outcomes for transmen.

The Cass Review says to stop puberty blockers on genreal prescription until they can be properly trialled. But any trial has to be ethical and I don't think there will ever be an ethical trial of puberty blockers on children. 15 years ago, yes, when the Tavistock said they were doing a trial but were actually not gathering any data; but not now. That ship sailed long ago. There's already too much other evidence of physical harm and not enough evidence of psychological benefit to compensate for it.

Once the follow up data for children who were given puberty blockers over the last decade or two has been prised out of the adult clinics and properly analysed, it is very likely that puberty blockade will be stopped permanently. There will be no possibility of an ethical trial.

I think we have to accept for a very small number of individuals including some under 18s, the distress and dysphoria they feel isn't able to be managed by any other means and once all other available options have been tried, for some this has to be an option, but the selection criteria and record keeping has to be immaculate so that outcomes and harms can be recorded and data collected.

It may be worse than that. I get a very strong impression that even experts can't identify the children whose dysphoria really needs to be managed like that and could not wait for adulthood (if there really any any, even that is not proven!), versus those who would simply outgrow the dysphoria under "watchful waiting", versus those whose dysphoria lasts and could be treated as adults. The main "other option" is "watchful waiting" which has a high success rate.

Before there were puberty blockers most dysphoric children did outgrow it, and even when puberty blockers arrived there was no relationship between the intensity of their childhood dysphoria and the likelihood of changing their minds.

So how could you hope to identify a group of children on whom to trial these drugs?

Yes.

We already know there are physical and mental harms from PBs - including in those who took them 'correctly' for precocious puberty. So for a propective human trial we'd need, as a minimum:

• Thorough retropective reviews and propective animal studies to ensure the short- and long-term harms are well enough understood for people to be able to give properly informed consent.
• Evidence from the retrospective reviews that it is at least reasonably likely that benefits outweigh the harms.
• To be able to reliably identify and exclude the 80+% of the presenting cohort who will naturally desist.

If those tests are met, and once we've landed all the airborne porcines, it could be worth considering whether it is possible to conduct an ethical prospective trial.

I think there's a reason why some clinicians in gender services were (allegedly) trying to get their patients not to co-operate with any evaluation of the services, not to consent to their data being used and so on. Such an evaluation would probably not reflect well on said clinicians or the treatment they offered.

This also highlights another ethical dilemma - the way that some practitioners use their patients as pawns in their own self-advocacy. "Give me loads of money or my patients will kill themselves" complete with pictures of little tear-stained faces. Isn't there any disciplinary control over people like that?

If anybody can find any papers showing a clear and statistically significant reduction in suicidality as a result of hormone treatments compared to other options, do drop the reference into the thread somewhere, if you have a moment, because I'd be most interested.

No, partly because they should have been keeping records and following up already. What they do have they wouldn't share with Hilary Cass.

Mostly because I don't think the future physical and mental development of children should be experimented with.

but then didn't measure IQ at the end of the trial

How do we know this? Because it wasn’t mentioned in the paper?

There is also evidence that puberty blockers damage cognitive function and development of sex organs. I'm not sure anyone would make a case that those losses would be justified by children feeling a bit better about themselves for a short period of time. A benefit which could also be achieved by better mental health support.

Study described here but no protocol available as yet.

A study into the potential benefits and harms of puberty suppressing hormones as a treatment option for children and young people with gender incongruence is being developed through the National Research Collaboration Programme (NCRP) in place between NHS England and the National Institute for Health and Care Research (NIHR). The NRCP joint programme provides a collaborative approach to study development; studies being progressed through this route still have to demonstrate that they can materially build the evidence base for potential future NHS treatment options, while meeting a high scientific bar in terms of research methodology, as well as securing other important research approvals, including ethics committee approval.
It is envisaged that children and young people in both England and Wales will be able to participate in the study with access through NHS children and young people’s gender services. A multi-disciplinary team approach will be taken to identify those children who, with the consent of their parents, may be deemed clinically suitable for consideration of puberty suppressing hormones through the study. Children participating in the study will also continue to receive comprehensive psychosocial support.
The study will measure a range of potential treatment benefits and harms (for example whether puberty suppressing hormones impact in a meaningful way on levels of anxiety or depression, on body image, or brain development) using a range of validated tools, questionnaires and user feedback. Key measures included in the study, and the way data are collected, will aim to bridge gaps in existing research and will also be shaped by engagement with a range of stakeholders, including children and young people referred into NHS gender services and their families or carers.
Professor Emily Simonoff has been confirmed as Chief Investigator for the study. Emily is Professor of Child and Adolescent Psychiatry at the Institute of Psychiatry, Psychology and Neuroscience, King’s College London, where she is also currently Head of the Department of Child and Adolescent Psychiatry and Director of the King’s Maudsley Partnership for Children and Young People. She has extensive research experience and is also academic lead for the Child and Adolescent Mental Health Services Clinical Academic Group at the South London and Maudsley NHS Foundation Trust. The research will be co-sponsored by King’s College London and the South London and Maudsley NHS Foundation Trust.

https://www.england.nhs.uk/commissioning/spec-services/npc-crg/gender-dysphoria-clinical-programme/implementing-advice-from-the-cass-review/cyp-gender-dysphoria-research-oversight-board/

Well spotted @RethinkingLife - many thanks indeed.

Surely in any clinical trial, the ethics of trying a drug that could cause serious harm to a child must be weighed against the harm caused by not using the drug? So with Lupron, the drug used to slow child cancer, the more harmful scenario is rapid terminal cancer growth. (Lupron is the drug that has since been co-opted for puberty blocking).

There is no proven harm to going through puberty for any child. Not a single iota of evidence other than manufactured ideology. So therefore not ethical to trial puberty blockers.

If anybody can find any papers showing a clear and statistically significant reduction in suicidality as a result of hormone treatments compared to other options, do drop the reference into the thread somewhere, if you have a moment, because I'd be most interested.

But such a trial is likely to be so biased as to be useless. We see time and time again how children and their parents are told suicide is the inevitable outcome of being denied PB that a reduction in suicidality would simply reflect an ingrained taught belief.

I am torn on this one. I don't think that the outright ban on PBs will hold without some high quality data that confirms that is the right decision. It is important to note the Cass review says the evidence of benefit is weak to non existent, but equally the evidence of the balance of harms versus potential benefits is equally weak.

I can't see another way to settle this other than to do the trials and do them well. This is likely to mean that some children will be harmed, but equally it could mean some will benefit. I will be really interested in the study design. The study can't be blinded. The experimental arm will be PBs, but what will the control arm be? Watch and wait? Talking therapy? Internet ban?? Also it will be incredibly challenging to ensure that the control and experimental arms are balanced as these kids are just so complex, it would be sooo easy to end up with biased samples in either group.
For example, if the autistic girls or the gay boys are over represented in either arm or the kids suffering from underlying trauma, it could massively sway the results.

The reality is if there is no legitimate route to source PBs people will resort to illegitimate routes, which will be so dangerous. I think doing this in a controlled way that will generate high quality data is the least worst option.

I dont see how this can be ethical.

It is important to note the Cass review says the evidence of benefit is weak to non existent, but equally the evidence of the balance of harms versus potential benefits is equally weak

This makes no sense. And is also is not what Cass says.

And in any event if the staring point is otherwise healthy children with multiple and complex mental health, dysphoric, identity, neurodivergent and hormonal differences, you have absolutely no clear starting point for a clinical trial of any description. And ‘some children may be harmed, hey ho!’ is nowhere near good enough for me.

No
By now surely we have enough evidence of its effects, why harm more, its unethical.
I would hope for better research and evidence collation of those who have taken it, and access all possible data to see how all their health markers have changed over time.
I imagine there are more than enough detransitioners on the reddit thread who might wish to take part in a large trial on that basis.

I agree.

Regardless of your position on how best to help them, reducing the effects of a huge life-changing treatment to "feel a bit better" is precisely the rhetoric that causes backlash. As previous contributors have noted, there is a concerted effort to stop people from co-operating with studies, and with characterisations like that, you can't blame them. Going through a life-changing process and having it reduced to "felt a bit better" is dismissive and harmful.

The key finding from Cass was that we do not know the long-term effects conclusively . So when you say "for a short period," how do you know this is correct? The evidence we have suggests sustained benefits during the duration of the studies.

Yes, there are serious risks to balance, but until we move beyond entrenched positions and honestly accept any benefits, it is impossible to have a sincere conversation where we weigh them against the risks.

Fnally, suggesting that better mental health support alone can achieve the same benefits overlooks the specific needs of these young people. A more nuanced and compassionate approach is necessary for a truly constructive discussion.

Yes, I'm sure there are many criticisms that could be mounted of such a study, which is why I'd like to see for myself. There's one here that comes close to what I'm talking about, though perhaps predictably there aren't any differences once controls are applied.
https://mentalhealth.bmj.com/content/27/1/e300940.full It's people being referred to gender specialist services, rather than hormones specifically. In some ways it's surprising that there aren't more start differences, given the amount of shroud-waving that some people indulge in.

This is entirely speculation on my part but I think, as with many other human troubles, the key therapeutic feature is having an intelligent-sounding adult taking you seriously and paying you loads of attention. Probably as powerful as any pharmacological effects of prescribed medication. Especially for kids who've had a persistent feeling that they don't fit in, and the map of masculinity or femininity that family, society and school lays out for them is deeply unappealing.

Sorry, that was meant to say 'stark differences' rather then 'start'

This was rated as a high quality study by Cass, I am nor saying it is exactly what you are asking for but it is certainly worth considering:

www.jahonline.org/article/S1054-139X(20)30027-6/abstract

Ok, so from memory of an interview with Dr Cass. She said that the rationale for puberty blockers was confused. One reason for using them was as a 'pause button' so children had time to think about whether they wanted to pursue transition or not. This has been proved to be false as 98-99% of all those who start blockers continue onto cross sex hormones. So any trial could not be based on this as the reason to use the blockers.

Another reason given was so that they will pass more easily as adults but for boys the puberty blockers cause problems with lack of tissue for a vaginaplasty since they stop the penis from growing. For girls you could stop periods with hormonal contraceptives which is much less risky than puberty blockers. And can anyone really justify using such powerful drugs for cosmetic results that are actually questionably beneficial?

Dr Cass said that the only group she could see that would benefit from puberty blockers would be the boys who socially transition very young, are stealth in all areas of life, and for whom puberty is a very scary prospect. But remember she recommended specialised intervention as early as possible and a holistic view of the child in any treatment so hopefully these boys can be supported from early on so that they do not get to the position of being scared of puberty because everyone around them believes they are a girl.

Given all this, I just can't who will be the children for whom puberty blockers could be recommended.