Puberty Suppressing Hormones, House of Commons, Wes Streeting taking a firm and intelligent stand

"The NHS has clearly left itself open to being sued, which is maybe another reason for conducting such a trial; so as to find some clinically approved reason for the use of puberty blockers for young people suffering mental and emotional distress."

The Tavi was operating like the Wild West. It didn't follow the standard protocols within medicine and their maverick approach infiltrated the endocrine clinic at UCL. Prior to the Cass review, this might have been possible. There are so many eyes on this now, that the level of scrutiny this research is attracting greater scrutiny to the ethical approval procedures and criteria etc.

I am a bit familiar with clinical trials (for anti-cancer drugs, though, so ethically the process is very different). My understanding is that puberty blockers followed by cross sex hormones will likely pose very different risks compared to puberty blockers followed by normal puberty. The duration of treatment is also different. Doesn't this imply that safety needs to be assessed specifically?

The question is what is this positive evidence and who collated it and under what circumstances? There is also evidence aplenty that there is negative consequence and that in many cases mental health deteriorates.

I suspect that there is a desire tro find good reasons for use..... That is certainly what I picked up on in Wes Streeting's recent speech.

I tend to use the term 'gender distress' to acknowledge the formulation that the patient holds. My formulations always go wider than gender and incorporate all the factors that could be/are contributing to the overwhelm/distress/poor functioning.

I have no idea what terms and definitions will be used in the research protocol, and subsequent study - if approved.

The NHS has clearly left itself open to being sued, which is maybe another reason for conducting such a trial; so as to find some clinically approved reason for the use of puberty blockers for young people suffering mental and emotional distress.

If the trials are going to be conducted with the primary purpose of monitoring mental health outcomes - why not use an established anti anxiety/depression medication? Puberty blockers were not intended for treating mental health conditions, and one can only assume that any positve impact of puberty blockers on mental health would in large part be a side effect of blocking puberty - so a kind of placebo effect which is secondary to the physical consequences.

I cannot believe that the NHS has allowed itself to be so captured in this way. It makes no medical or scientific sense at all...not to me, anyway.

Young people and/or their parents want to block their natural puberty because they believe they are in the wrong body and should have the puberty of the opposite sex. This is clearly a crazy idea that should never have been entertained in the first place.

As a mental health professional can you point me towards a definition of the condition in children which this trial aims to treat?

Gender dysphoria was originally classified as a mental health condition, but I think it has been moved (in one of the diagnostic manuals, at least) to 'sexual health'. It's unclear how a sexual health condition in adults relates to what appears to be a mental condition in children.

The NHS website used to have a definition of gender dysphoria in children which was almost exclusively based on stereotypes (with a nod towards dislike of the sexual organs). It no longer gives any definition at all.

Before any trial takes place, surely it first has to be defined exactly what the condition is that is being treated and how these drugs aim to alleviate the symptoms.

Thanks @kiterunning. My comments are tentative (I tried to phrase them as such) as I have no insider knowledge about the proposed research. Also, whilst I have experience of being part of a REC, my background is mental health, not medicine.

@Brainworm
Thank you for sharing your knowledge!

"And would also need to exclude from those who are functioning so poorly and in dire distress, the children who may be functioning poorly due to autism/trauma/family issues etc."

This is an interesting aspect as there are equality issues to consider. Back in the day, we used to control for lots of confounding variables through exclusion criteria but there is now an expectation (and legal requirement) to be inclusive.

I am sympathetic to this argument in many ways. Drugs have mostly been trialled on male populations only as women (with their pesky menstrual cycles and pregnancies etc) were excluded. This makes women less protected.

If there is a potential benefit to a drug, children with protected characteristics shouldn't be excluded from participating in trial unless there is a strong reason for doing so. Similarly, if there are significant questions about potential risks/benefits, children without protected characteristics shouldn't be used as 'cannon fodder' whilst protecting the 'most vulnerable'.

The easiest way to get through the REC would be to only include those who are experience very high levels of distress and for whom current quality of life is dire (e.g not going to school, rarely leaving the house, not eating, self harming etc.). It will be difficult to justify the potential risks for populations who are functioning relatively well on a daily basis.

And would also need to exclude from those who are functioning so poorly and in dire distress, the children who may be functioning poorly due to autism/trauma/family issues etc.

The original Dutch study at the root of this intervention only included those with no co-morbidies and otherwise healthy functioning and stability at home.
So this wouldn't this then be the opposite to that?

"Can you point me to some information about a similar trial to this one: where a drug has been approved for use in a physical condition, and is being trialled for use in an unrelated mental condition?"

Have a look into Lamotrigine. It was originally licensed for epilepsy but is now also used for bi-polar disorder.

"Didn't the earlier trial show that mental health for many children deteriorated when taking these drugs? Wouldn't it be hard to justify damaging the bodies of physically healthy children in order to try to improve their mental health, when there is no evidence from previous experiments that this 'treatment' is effective, and in fact may cause a deterioration in their mental health?"

This is the crux of it. There is conflicting evidence. If there wasn't any evidence indicating positive outcomes, it would be hard to get through REC. I think there is evidence indicating efficacy in the form of case studies and testimonies. There is some evidence for this not being the case more generally. Cass highlighted that there isnt a clear picture.

The REC will need to decide if the potential for positive impact outweighs the risks.

Can you point me to some information about a similar trial to this one: where a drug has been approved for use in a physical condition, and is being trialled for use in an unrelated mental condition?

The easiest way to get through the REC would be to only include those who are experience very high levels of distress and for whom current quality of life is dire (e.g not going to school, rarely leaving the house, not eating, self harming etc.). It will be difficult to justify the potential risks for populations who are functioning relatively well on a daily basis.

Didn't the earlier trial show that mental health for many children deteriorated when taking these drugs? Wouldn't it be hard to justify damaging the bodies of physically healthy children in order to try to improve their mental health, when there is no evidence from previous experiments that this 'treatment' is effective, and in fact may cause a deterioration in their mental health?

"Phase 4 appears to come into play after the drug has been approved for use"

When an approved drug is being trialled for purposes that differ to those they are licensed for, the first 3 stages don't need to be repeated. PBs have been approved for use in children with precocious puberty. The proposal is to now trial them for use with children with gender distress.

There will be an information sheet that outlines the risks of participating in the study. This will include any known/anticipated potential side effects.

I think the risk of litigation relating to side effects is limited if potential risks are clearly explained in the information sheet and they have been deemed by the REC to be reasonable when considered against the potential benefits.

I am very interested in their inclusion criteria. The easiest way to get through the REC would be to only include those who are experience very high levels of distress and for whom current quality of life is dire (e.g not going to school, rarely leaving the house, not eating, self harming etc.). It will be difficult to justify the potential risks for populations who are functioning relatively well on a daily basis.

I think a Stage 4 drugs trial will be conducted to explore efficacy in the short/ medium term. Stage 1-3 trials have already been conducted for PBs with child populations, so only a Stage 4 trial is needed to explore off label use.

I'm not familiar with the jargon used here, but fortunately there's lots of information on the Web about clinical trials and what is involved in the different stages. Here, for example.

Why do you say Stage 1-3 trials have already been conducted?

From my link:
If a drug can show an improvement over the standard treatment in a phase 3 clinical trial and is safe to use, it is likely to be approved by regulatory authorities so that it may become the new standard treatment for patients with that disease.

I think we are a long way from halting puberty in healthy children being shown to be safe and the most effective treatment for this mental condition.

Phase 4 appears to come into play after the drug has been approved for use.

So would there be a risk of legal action if those on the trial develop bone/brain abnormalities further down the line?

Vikki Slade mentioned near the start is Lib Dems

Yes, the type of medication seems unique for this condition.

Medication for mental conditions are normally designed to cure or alleviate the mental symptoms or, if there is a physical cause, to heal or cure the physical illness which is causing mental distress.

I don't think there are any other conditions where the treatment for a mental health condition is to make the physical body less healthy, or to cut off healthy body parts.

"Are there any other medications, apart from psycho-actives, that are used to treat mental health - but which have possible, and profound, long term physical impacts? Any negative effect of puberty blockers on the developing brain and body would not be seen in the immediate short-term; so how can trials be short term and/or time controlled?"

I'm not sure the 'other medications used to treat mental health' comparator will come into play with REC, they will look at the research protocol on its own merit.

Drugs trials are different to longitudinal studies and I expect there will be at least 2 related studies taking place.

I think a Stage 4 drugs trial will be conducted to explore efficacy in the short/ medium term. Stage 1-3 trials have already been conducted for PBs with child populations, so only a Stage 4 trial is needed to explore off label use.

I expect a longitudinal study will also be conducted to explore long term outcomes and side effects. This research is likely to last decades.

Actually, that doesn't quite make sense as a partial lobotomy will remove parts of the brain.

The pruning phase of development is a natural removal of connections that is essential for the change from childhood to adulthood.

So it's not the same thing but it logically has a similar net effect. It's the natural functioning (the essential pruning) that has been "lobotomised". In both cases, the brain is no longer able to work as it would have done otherwise.

Are there any other medications, apart from psycho-actives, that are used to treat mental health - but which have possible, and profound, long term physical impacts?

Not sure. But partial lobotomies spring to mind.

Puberty blockers are almost a chemically induced partial lobotomy because they prevent the "pruning" phase of brain development from happening in adolescence.

Are there any other medications, apart from psycho-actives, that are used to treat mental health - but which have possible, and profound, long term physical impacts? Any negative effect of puberty blockers on the developing brain and body would not be seen in the immediate short-term; so how could a meaningful trial be short term and/or time controlled?