Puberty Blockers clinical trial.

[PlainJane999]

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

It’s possible to agree with the findings of the Cass Review but not fully agree with all of the recommendations. Not agreeing with some parts of it doesn’t mean it taints the rest. That’s “you align with so and so, ergo you’re a Nazi!” type of thinking.

Before you even discuss the implications of the treatment with puberty blockers, both the harms and the potential gains, you need to indicate how you are selecting your population.

First show me how you accurately select a large group of 10-12 year olds who are going to have a persistent cross sex identity who might potentially benefit from puberty blockers, before any discussions around treatment implications. No one can do this. No one pro PBs can do this. Prove me wrong.

I don't think that the outright ban on PBs will hold without some high quality data that confirms that is the right decision.

But the implication of this is horrific - ‘we need to carefully record children being harmed in order to uphold an outright ban’

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.

In other words, children who have deceived others and are afraid of their deception becoming public. That is no reason for giving any child drugs.

Yes, this is the sort of thing - many thanks indeed.

I see De Vries is among the authors so it's some of the usual suspects marking their own homework! Even so, you can see the differences in scores on the measures, in favour of the hormones. I think some of @Sloejelly 's observations are relevant here. The hormone group are on a programme which they've been told is the one that'll save their lives. If not by the research assistants handing out the questionnaires then by the wider culture. The ones just getting psychosocial support know they've got the booby prize so they're going to be a bit peed off. Something the authors don't talk about is co-morbidities and I'm curious as to how comparable the groups were in this respect - I'm sure we've all seen the stuff in the UK about young people seeking "gender affirming care" being likely also to have autism spectrum symptoms. So I wonder if the groups in Van Der Miesen et al were comparable in terms of this and other possible co-morbidities. As it's not a random assignment study, I wonder if there were any factors that predisposed the clinicians to put some people on the hormonal pathway and not others - if they've been working in the area for a while they'll have a gut feeling about who might "benefit" (if you can call it that) which might inform decisions.

So I'm not disputing Cass's judgement, I'm just saying the results of this kind of thing need interpreting with caution.

No matter - in the discussion the authors really let themselves off the leash with a paean to the Dutch model, gender affirming care and puberty blockers! For a moment I thought I was on the mermaids website rather than in an academic journal.

Thanks for linking this. Unfortunately the full paper is behind a paywall and the abstract does not give much information. However it is a cross sectional observational study, not a trial, so at best of mid quality not high quality. But against a background where it is already known that children are coached in what to say in order to obtain PB drugs it is hardly surprising that they would report higher levels of suicidality prior to obtaining drugs. What the paper does not do is assess the impact of psychotherapy and whether talking therapies could have an equal or better outcome than profoundly harmful drugs.

AlexaAdventuress thanks, for your assessment of the full paper

It's on the authors' university website
Psychological Functioning in Transgender Adolescents Before and After Gender-Affirmative Care Compared With Cisgender General Population Peers (uva.nl)
I'd be interested in what @Sloejelly 's gimlet mind could make of it. Or anybody else's observations, of course.

Would you like to suggest how such a study would deal with the euphoria effect that may be experienced in receiving the drugs that support groups tell children that will start their transition? How do we account for that short term?

Or do you think this study will last 10 years and assess the patients at a 10 year mark?

Why assume lack of consent? Is it because TRA's have been urging for consent to be withheld?

Children want puberty blockers because of a bloody ideology, largely pushed by adult male cross-dressers. Who are also now sabotaging attempts to discover the long-term effects. And other clinics are withholding their research!

You will have to forgive people for concluding that this is one massive con and that no, children should not be sacrificed to perpetuate it.

I note the treatment group are older than the pre-treatment GD group (and non-GD comparison group) Both GD groups also are more likely not to have ‘both parents’. But the biggest difference between the GD group and the comparison is education level. The Dutch have three levels of secondary schooling depending on academic ability. Over 70% of the GD group were attending the lowest tier, compared to just 15% of the comparison group.

You mention the pre-treatment group as “just getting psychosocial support know they've got the booby prize so they're going to be a bit peed off” but actually there is no mention of getting psychosocial support at all. Just a group who just arrived and may well be motivated to get PB, and a group in receipt of PB and about to start cross sex hormones and may also be motivated to show that PB are working for them in order to access CSH.

Can you provide any actual evidence to support your claim that children are coached to report higher suicidality within the context of this or a similar study? The improvements in mental health were observed post-treatment, reducing the likelihood of manipulated assessments to game the system.Moreover, the study was conducted in the Netherlands, where access to gender-affirmative care is less restricted compared to the UK and many other countries. This difference likely leads to more accurate and less pressured self-reporting. Combined with the large sample size and reporting technique, I strongly disagree with your assessment and agree with Cass that it is a high-quality study.

As you rightly point out, this particular study is cross-sectional, but it is worth noting that long-term longitudinal studies are precisely the type of evidence Cass has highlighted is missing. I believe studies like this one, although not perfect, provide a level of confidence to continue with the research instead of shutting it all down.

"The present study can, therefore, not provide evidence about the direct benefits of puberty suppression over time and long-term mental health outcomes."

From the paper itself.

Now, if you’re going to continue the research into puberty blockers, how do you accurately select a group of children who are going to have a persistent cross sex identity to work out whether this cohort have a benefit from puberty blockers?

Can you provide any actual evidence to support your claim that children are coached to report higher suicidality within the context of this or a similar study?

Read Cass.

As you rightly point out, this particular study is cross-sectional, but it is worth noting that long-term longitudinal studies are precisely the type of evidence Cass has highlighted is missing.

A cross-sectional study is not a long term longitudinal study. There is only a single time point, no followup. There was no ‘improvements in mental health post treatment’ only a group that was two years older filling in a self reporting questionnaire prior to being granted cross sex hormones. We have no idea what their mental health was prior to receiving PB, what their mental health would be like if they had not received PB, or what it would have been like if they had received talk therapies.

I think everyone in this thread has repeatedly acknowledged in the lack of evidence specifically in the long term area. It is exactly what Cass is calling to be fixed and why we are discussing 🤦‍♀️ so if this is meant to be a gotcha then please read the thread.

As for picking who should be on such a study. You cannot predict with 100% accuracy but that is the same for any medical reaserch. I imagine participation would be a highly personal decision made beteen the medical professionals and the family. The alternative of doing nothing carries a different set of risks, it all needs to be weighed up on an individual basis.

Quite. We don’t need a clinical trial of thalidomide in pregnant women in order to ban it from being used in that population. There is enough evidence of harm without clinical studies.

It isn’t banned outright, it’s a useful medication for some diseases like leprosy. But the use has to be very closely monitored.

@PlainJane999 , what circumstances do you believe would make it appropriate to prescribe puberty blockers, in any situation other than precocious puberty?

No problem with a trial being set up.

But there needs to be enormously rigorous procedures, which are tested for independently of the trial scientists, to ensure that every child enrolled on any such trial is mature enough to fully understand the impact of what is going to happen, has all the long term likely impacts fully explained (loss of fertility, never gaining the ability to orgasm, never growing sufficient flesh in the genital area to allow for future surgery, reduction in intellectual function, bone and joint problems etc) and can demonstrate a full understanding that neither these drugs nor any following surgery will ever change the fact that every cell in their body contains the genes of their biological sex. Obviously as the child will be under age the parents must be fully informed about all this too and must be freely able to either consent or not consent to their child undergoing these risks, without being put under emotional pressure. The trial must also exclude anyone whose mental health is fragile especially anyone who has threatened or attempted self harm or suicide. The enormous potential for known harms needs to be balanced by an enormous weight of proof that every subject in the trial is fully capable of comprehending the risks and is fully competent to choose whether or not to take them.

I do not believe that any such trial will be able to recruit a statistically significant number of participants and any lesser conditions for participation would be unethical in the extreme so the trial will forever be technically in the process of being set up but practically will never actually happen.

You have not understood the point I am making here. I am fully aware of the differences between the two.

My point is that you seemed to be only accepting of a long-term longitudinal study. When we all know this does not exist to a satisfactory level. Therefore, asking for links to such studies is futile.

I think that families and their medical professionals should have blockers on the table as an option (as per Cass, used with caution)

Where I disagree with Cass is that if the reaserch participant numbers can be reached voluntarily, then forcing people to be on a study seems un-ethical.

As a option for what?

We should not be medicalising kids who are gay, lesbian, autistic or non conforming to expectations. We should not be haulting the puberty of kids who do not obey society's performance rules.

This is an invented distress and a made up drug regime to treat it.

@PlainJane999 I'd like to know your opinion as to why van der Miesen et al. didn't do a longitudinal study?
The study they did compared three cohorts at one point in time. Even if they'd started there, by now they could have a four year study, which would be fantastic data!
Why has no one done a longutudinal study in this area of medicine?
I'm a nurse, I know we give children all sorts of horrendous treatments because benefits outweigh harms over all. Think of paediatric oncology, for example. Paediatric gender medicine is /such/ and outlier in the way it has progressed. In every other area of paediatric medicine the null hypothesis for an intervention, any intervention, is that there is no overall benefit to providing it. Research needs to prove otherwise before it becomes protocol. Before. I don't know what the trials Cass recommends will look like. I'd assume they'll try to get statistically significant data from retrospective trials so that they don't have to do any prospective trials, but it's all a very strange beast to manage because protocal was developed before benefit was demonstrated.
I was really pleased when you shared the link to this paper but I'll be honest my heart sank when I saw what counted as high quality evidence. Children deserve so much better.

It’s not a gotcha. It’s pointing out the paper itself doesn’t claim to be evidence for puberty blockers.

As for picking who should be on such a study. You cannot predict with 100% accuracy but that is the same for any medical reaserch. I imagine participation would be a highly personal decision made beteen the medical professionals and the family. The alternative of doing nothing carries a different set of risks, it all needs to be weighed up on an individual basis.

It’s not remotely the same. That’s the point. It’s completely different.

Take the diagnosis of pre-adolescent gender dysphoria as per the DSM 5 TR criteria. It is a diagnosis wholly based and dependent on societal stereotypes. A child who might be eligible for a puberty blockers trial can only get an eligible diagnosis if a clinician believes in these societal stereotypes. It’s entirely subjective.

Can you name another area of medical research that is conducted on a condition reliant on societal stereotypes? Medical conditions are not subjective. There shouldn’t be any opinion on whether a cancer is there or not.

How does a research team ethically block the puberty of children whose diagnosis is based on these subjective stereotypes?

Then consider the symptoms of this vague condition that children acquire as their diagnosis. We know that for the majority, these symptoms will abate. This is what’s known as the natural history of the condition.

Can you name another area of medical research where trials have been done on interventions for conditions that abate in 80% of cases?

I imagine participation would be a highly personal decision made beteen the medical professionals and the family.

But that’s what happens now. Parents and children are no longer told that if they wait, their distress will likely settle. They make a choice based on the information they are given. But we are not talking about that. We are talking about setting up a research trial. If the eligibility criteria is “anyone who wants them” then that ignores the entire ethical debate around diagnosis and natural history, which is a big part of the equation of how we got into this mess in the first place; people started blocking puberty of children based on stereotypes.

You cannot diagnose if you don’t believe stereotypical nonsense. You cannot predict which children will persist. Which means you will inevitably sterilise and render sexually dysfunctional children who wouldn’t have been diagnosed if they’d seen a different clinician and wouldn’t have been given any hormonal treatment if they had seen a different clinician.

It seems you’re advocating for a clinical trial that bypasses the ethical dilemmas of the very first stage of a trial: eligibility. Why do you believe this area should be bypassed and just left to patients and doctors to decide who gets a chance?

And that’s without even getting to the ethical dilemmas of knowingly sterilising children, rendering them anorgasmic, IQ reduction, bone density, consent issues etc.

The alternative of doing nothing carries a different set of risks, it all needs to be weighed up on an individual basis.

I don't think "doing nothing" is what is being proposed as an alternative.

The alternative is talking therapies to alleviate the child’s distress. What risks do you think there are in this treatment?

It seems you’re advocating for a clinical trial that bypasses the ethical dilemmas of the very first stage of a trial: eligibility. Why do you believe this area should be bypassed and just left to patients and doctors to decide who gets a chance?

OP, do you agree with this?

Also, can you say what your interest in this is? Is it personal for you?