NICE Evidence Review for Use of Puberty Blockers for GD - Now Released

[IDontOnlyLikeJazzFunk]

now released. NC. The full link is below, this is the summary. It's not looking good.

Discussion
A key limitation to identifying the effectiveness and safety of GnRH analogues for children and adolescents with gender dysphoria is the lack of reliable comparative studies. The lack of clear, expected outcomes from treatment with a GnRH analogue (the purpose of which is to suppress secondary sexual characteristics which may cause distress from unwanted pubertal changes) also makes interpreting the evidence difficult.

The studies included in this evidence review are all small, uncontrolled observational studies, which are subject to bias and confounding, and all the results are of very low certainty using modified GRADE. They all reported physical and mental health comorbidities and concomitant treatments very poorly. All the studies are from a limited number of, mainly European, care facilities. They are described as either tertiary referral or expert services but the low number of services providing such care and publishing evidence may bias the results towards the outcomes in these services only and limit extrapolation.

Many of the studies did not report statistical significance or confidence intervals. Changes in outcome scores for clinical effectiveness and bone density were assessed with regards to statistical significance. However, there is relatively little interpretation of whether the changes in outcomes are clinically meaningful.
In the observational, retrospective studies providing evidence on bone density, participants acted as their own controls and change in bone density was determined between starting GnRH analogues and follow up. Observational studies such as these can only show an association with GnRH analogues and bone density; they cannot show that GnRH analogues caused any differences in bone density seen. Because there was no comparator group and participants acted as their own controls, it is not known whether the findings are associated with GnRH analogues or due to changes over time.

Conclusion
The results of the studies that reported impact on the critical outcomes of gender dysphoria and mental health (depression, anger and anxiety), and the important outcomes of body image and psychosocial impact (global and psychosocial functioning), in children and adolescents with gender dysphoria are of very low certainty using modified GRADE. They suggest little change with GnRH analogues from baseline to follow-up.

Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance. It is plausible, however, that a lack of difference in scores from baseline to follow-up is the effect of GnRH analogues in children and adolescents with gender dysphoria, in whom the development of secondary sexual characteristics might be expected to be associated with an increased impact on gender dysphoria, depression, anxiety, anger and distress over time without treatment. The study by de Vries et al. 2011 reported statistically significant reductions in the Child Behaviour Checklist (CBCL) and Youth Self-Report (YSR) scores from baseline to follow up, which include measures of distress. As the aim of GnRH analogues is to reduce distress caused by the development of secondary sexual characteristics, this may be an important finding.

However, as the studies all lack appropriate controls who were not receiving GnRH analogues, any positive changes could be a regression to mean.

The results of the studies that reported bone density outcomes suggest that GnRH analogues may reduce the expected increase in bone density (which is expected during puberty). However, as the studies themselves are not reliable, the results could be due to confounding, bias or chance. While controlled trials may not be possible, comparative studies are needed to understand this association and whether the effects of GnRH analogues on bone density are seen after they are stopped. All the studies that reported safety outcomes provided very low certainty evidence.

No cost-effectiveness evidence was found to determine whether or not GnRH analogues are cost-effective for children and adolescents with gender dysphoria.

The results of the studies that reported outcomes for subgroups of children and adolescents with gender dysphoria, suggest there may be differences between sex assigned at birth males (transfemales) and sex assigned at birth females (transmales).

arms.nice.org.uk/resources/hub/1070905/attachment

I read a comment here a while ago about a class action lawsuit regarding the use of PB's, may have been about their use in treating precocious puberty? Does anyone know if that's happening, because I can't remember if what I read was speculation that there'll be a lawsuit, or there actually is one.

I've tried Googling but I just get the Bell v Tavi articles.

@vivariumvivariumsvivaria

Well, I mean that they have "patients" (for want of a better word) in positions of authority within the organisation. Who then steer the approach, which has massive influence in the NHS and government and organisations.

Everything else in health care works from evidence first, not from patient desire first.

I genuinely can't think of any other field of healthcare where the patient/client is given such authority. THey'll listen to patient experts, they'll consult and work with them, but, the decision making is firmly based on evidence, not on what the patient believes they need.

I posted this on another thread about the Tavistock yesterday, where the minutes of the board of directors meeting were being discussed.

tavistockandportman.nhs.uk/documents/143/board-papers-2015-07.pdf

On p 8-9, there is a report of two young patients at GIDS speaking to the board, and it includes this:

Ms I added that she appreciated that the Trust was involving her and the other young people in the service, getting their feedback, and listening to their point of view. She added that they had sat on an interview panel that morning, and it was really good to be on the other side of the table for once.

It doesn't give any information about the interview in question, but it struck me as odd that two very young people (as current patients they must have been under 18), were asked to do this.

@Manderleyagain

Is NICE for the whole of the UK, or it only England and Wales? The clinic in Glasgow didn't change anything in response to Bell because it was English high court, but will they have to respond to this?

England and Wales though Scotland normally take on their reports. The scottish equivalent is SIGN (Scottish Intercollegiate Guidelines Network) but they are a lot smaller operation.

@yourhairiswinterfire

I read a comment here a while ago about a class action lawsuit regarding the use of PB's, may have been about their use in treating precocious puberty? Does anyone know if that's happening, because I can't remember if what I read was speculation that there'll be a lawsuit, or there actually is one.

I've tried Googling but I just get the Bell v Tavi articles.

I think it might be in the US - Lupron is a GnRH which is a prostate cancer drug also used to treat endometriosis (unsuccessfully in almost all cases), fibroids and precocious puberty. I'm not sure what progress the proposed class action is making.

People administering the drug to a patient have to wear full ppe and avoid trying to conceive a child for 3 months.

25,000 adverse events reported, 25 deaths, a reported serious side effects list as long as your arm. I am wondering why anyone would be prescribing that to anyone ever.

The puberty blockers prescribed in the UK are the same class of drugs but hopefully they are of some sort of type that is less harmful than Lupron??

nwhn.org/lupron-what-does-it-do-to-womens-health/

@Manderleyagain

Is NICE for the whole of the UK, or it only England and Wales? The clinic in Glasgow didn't change anything in response to Bell because it was English high court, but will they have to respond to this?

NICE largely is NHS England and Wales.

The exception is when, for various reasons, the work together with SIGN for NHS Scotland and the special section for NI.

It's exactly the same chemically "05IDontOnlyLikeJazzFunk* It's just named differently in different countries

I believe there are other types of PBs, I remember googling it once and it's not specifically lupron used in nhs GIDs, but I can't remember exactly what.

I was just trying to find the difference types and I stumbled across this.

It was to be reviewed in 2019 and ran out last year.

Interesting in the light of the nice review.

There's a great deal of info on how nhs GIDS work, including references to WPATH and the Dutch protocol.

NHS STANDARD CONTRACT
FOR GENDER IDENTITY DEVELOPMENT SERVICE FOR CHILDREN AND ADOLESCENTS
SCHEDULE 2 – THE SERVICES A. SERVICE SPECIFICATION

www.england.nhs.uk/wp-content/uploads/2017/04/gender-development-service-children-adolescents.pdf

Thank you IDontOnlyLikeJazzFunk, sounds like that is what was being referred to in the post I saw.

The NHS offers Triptorelin. It's not the same drug.

It was noted on another thread that parents are not given free reign to do what they want with their children. They cannot consent for a child to get a tattoo for example. Nor can they consent for their child to be married. Parental authority over their child is limited.

Yes, something that was heavily bearing on the Charlie Hard and Alfie Evans cases with the right of the child is paramount and parents do not have the final say. Surely Bell will have less (none) effect on Gillick then the GLP railroading will have on the Convention for the rights of the child.

It sure is a mess, and it is such a mess because things have allowed for the train to not only have any brakes, there are no blinking rails in the first place.

I was screening some publications this morning (reasons) and saw a description of surgery (not a GID related topic) that read like it could be an RCT but seemed flirting with ethical issues to do it that way. I was about to pass it by but noticed the data (the 1970s) so decided to take a closer look. It was a randomised trial - the past was another country.

So after those three things surely what we have is a situation where a) only parents/carers can decide ultimately that their child should take these drugs b) any ethical doctor can only ask those parents "do you consent to this experiment" not "do you consent to this medical treatment"

TheMost I don’t think that’s quite right. For the treatment to be experimental it would need to be part of a clinical trial. This is off label (unlicensed) use of a medicine that is licensed for another purpose (pausing precocious puberty or threatment of prostate cancer, depending on which one is used). It’s perfectly legal to prescribe off label, but the prescriber takes additional responsibilities for safety and efficacy: www.gov.uk/drug-safety-update/off-label-or-unlicensed-use-of-medicines-prescribers-responsibilities

It’s difficult to see how the prescribing of these medicines for preventing puberty can possibly meet the requirements of the bullet pointed list at the end of the article. I would be disappointed if off label use of these medicines doesn’t appear in an updated version, as well as some clarification around the communication of off-label status, but I guess the MHRA is a bit busy at the moment...

NHS STANDARD CONTRACT
FOR GENDER IDENTITY DEVELOPMENT SERVICE FOR CHILDREN AND ADOLESCENTS
SCHEDULE 2 – THE SERVICES A. SERVICE SPECIFICATION

www.england.nhs.uk/wp-content/uploads/2017/04/gender-development-service-children-adolescents.pdf

That's the contract that the NHS has with GIDS. As you say there is a lot of cut n' paste from WPATH and the various lobby groups were consulted on the type of service they wanted as well as the wording of the document.

I believe the Cass review and the evidence from NICE will provide the foundations for a new service specification going forward.

England and Wales though Scotland normally take on their reports. The scottish equivalent is SIGN (Scottish Intercollegiate Guidelines Network) but they are a lot smaller operation.

I emailed SIGN this morning to ask about any response to the NICE review or whether it is worth doing a topic proposal.

It’s triptorelin that’s used in the UK, which is a different drug from Lupron, but very similar effects.

I was on it for six months, and it is an appalling drug. I was given it for endometriosis (a disease that only affects women, of course). It is not particularly effective for that, either.

The side effects were horrendous, and it may have caused lasting health effects, likely caused my infertility, and was likely one of the causes of my extremely early menopause, which is currently threatening to wreck my previously very successful career. In my opinion, it should never be given to children whose bodies and brains are still developing. And Particularly not for childhood gender identity disorder, with its vague diagnostic criteria and the utter paucity of evidence of efficacy.

I’ll never not oppose its use.

(No sympathy required, by the way, I am fine really )

@rogdmum

England and Wales though Scotland normally take on their reports. The scottish equivalent is SIGN (Scottish Intercollegiate Guidelines Network) but they are a lot smaller operation.

I emailed SIGN this morning to ask about any response to the NICE review or whether it is worth doing a topic proposal.

I'd be surprised if SIGN wanted to repeat an evidence review (which is what NICE did) - the interpretation of the evidence and operationalisation (so to speak) would be up to the equivalent of the NHS E Working Group (the Cass Review) if there is one.

@DadJoke

The NHS offers Triptorelin. It's not the same drug.

thanks Janie and gosh! Sophocles that sounds terrible!! Thanks Dadjoke - do you happen to know if Triptorelin is the only puberty blocker offered by the NHS or are there alternatives?

If it is the only one I wonder how they have decided to use that particular one (in the absence of good data). It is interesting that for a condition that involves depression or anxiety, the known side effects for Triptorelin include: Depression, mood altering and possible side effects are anaphylactic reaction, haemorrhage, nausea, vaginal discharge and vomiting.

One of the uses of Lupron in the US is for endometriosis and it seems that it has been found to be almost entirely ineffective for that purpose so it is a bit bizarre that they have been prescribing for that.

The NICE website lists the following in this group of drugs for precocious puberty (obviously nothing recommended currently for gender dysphoria). It is my understanding that these are Gonadotrophin Releasing hormone Analogues (GNrH) and therefore of the same class as Lupron.

Gonadorelin
Lueprorelin acetate
Triptorelin

Obviously living in hope these drugs are not as toxic as Lupron, (although Sophocles' experience sounds pretty bad) - it would be quite appalling if they were. It does beg the question however, that if there are alternative drugs available that do the same job as Lupron, but with significantly less dangerous side effects, why on earth are the Americans prescribing Lupron for anyone?.

We also have a slight issue in the UK where there are a number of private clinics and GenderGP who are prescribing puberty blockers to children and no one has any idea what they are prescribing. They are actively working against any safeguarding guidelines, will prescribe to children without the knowledge of their parents so can we trust them to prescribe the 'safest' version of pbs (if you can call it that)?

There are also children being encouraged by certain groups to buy their medication over the internet - who knows what they are buying - obviously there are Americans who are very prepared to sell Lupron quite openly - again, there is no way of knowing what the children are buying.

These are not for sympathy Sophocles, just because it's a lovely spring day and the daffs are out.

Speaking of Harry Benjamin.....

https://www.theguardian.com/us-news/2021/apr/01/trans-children-history-jules-gill-peterson-interview

(It's April 1st...)

If you buy drugs off the internet then you have no certainty what the drug actually is and even if it is the correct drug you cannot be sure of its concentration, age or how it has been stored. Fake drugs are a huge and growing problem that even the NHS can be caught out by on occasions.
In addition triptorelin is administered by injection so then there issues around safety of individuals self-injecting and sterility of needles etc bought off the internet.

Thanks, idont and arabella

I only bring up my personal experience because we’re so often accused of not having skin in the game. I also do...enjoy isn’t the right word...but wryly note that for all trans allies are about need to respect lived experience and personal truths, I have yet to have a single drop of empathy from one for my own lived experience with this. The well of empathy runs dry when it’s women’s experiences, of course. But it’s interesting anyway.

Derail over. Back to protecting children from experimental protocols.

I'd be surprised if SIGN wanted to repeat an evidence review (which is what NICE did) - the interpretation of the evidence and operationalisation (so to speak) would be up to the equivalent of the NHS E Working Group (the Cass Review) if there is one.

I doubt they would want to repeat an evidence review, but they should have a view on the NICE review. I’d think the interpretation/operationalisafion would be down to NGICNS.

@Sophoclesthefox

Thanks, idont and arabella

I only bring up my personal experience because we’re so often accused of not having skin in the game. I also do...enjoy isn’t the right word...but wryly note that for all trans allies are about need to respect lived experience and personal truths, I have yet to have a single drop of empathy from one for my own lived experience with this. The well of empathy runs dry when it’s women’s experiences, of course. But it’s interesting anyway.

Derail over. Back to protecting children from experimental protocols.

I do have interests in this puberty blocker information, although not as a patient/client. As far as I'm aware, a considerable percentage of the young people on the waiting list/seeing GIDS with regard to gender identity are also autistic. GIven my own experiences of autism, and supporting autistics with learning difficulties, some of the information I've seen has been terrifying.

"protecting children from experimental protocols."

Exactly. Oh, and I am a trans ally..... but I do worry, hugely, about puberty blockers, and their possible long-term effects.

I’m wondering what all this means for the Tavistock’s appeal. NICE think the evidence is poor quality and their own research didn’t back up their treatment pathway.
Are they saying that children can consent to a treatment where there is little evidence of it having any benefit and growing concern that it may be harmful. The judges specifically asked about their research during the first instance hearing.

Khawa like most people, I want to see proper safeguarding for all children, robust new research where NICE has shown that research is needed, medical professional objectivity, democratically-agreed external regulation of medical professional’s work. I want proper patient information and patient consent, better mental health support for distressed children, and public information and open discussion when issues arise from medical practice and research (or arise from the lack of research). Most people also think patient organisations should advocate on the basis of evidence of benefit to their members- rather than advocate on politics even if the practical impact of that on their members might not be good.

It’s completely understandable that people are asking why some groups and organisations are so adamant that kids must have access to treatments like puberty blockers, when there’s not solid evidence to show they help them.

Many patient organisations fundraise to fund research themselves, and almost all patient charities have a mission to advocate for government or NGO funded research into their specific health area. They want to make sure their members can have up to date evidence-based treatments. Not here though.. why not?

But all this is just ‘conspiracy theories’