Cochrane systematic review on effectiveness of puberty blockers

[Signalbox]

Brilliant and long overdue! Genspect are reporting that the Cochrane Collaboration are carrying out a systematic review on the effectiveness of puberty blockers and cross-sex hormones for gender dysphoria in adolescents.

Genspect twitter thread here...
twitter.com/genspect/status/1625890490154381313

Info about Cochrane here...
www.cochrane.org/about-us

What are systematic reviews?
www.cochrane.org/our-evidence/what-are-systematic-reviews

Interview with Dr Steven Levine (who is a member of the subcommittee preparing the review) here...
gender-a-wider-lens.captivate.fm/episode/60-pioneers-series-we-contain-multitudes-with-stephen-levine

Genspect twitter thread...

"Great news: Dr Stephen Levine is an invited member of a Cochrane Collaboration subcommittee currently preparing a systematic review of the scientific literature on the effectiveness of puberty blocking hormones & cross-sex hormones for gender dysphoria for adolescents.

Cochrane Reviews are a well-respected cornerstone of evidence-based practice, comprising a systematic review that aims to identify, appraise, and synthesize all the empirical evidence that meets pre-specified eligibility criteria in response to a particular research question.

Dr Levine recently submitted an amazing expert affadavit in the Wisconsin case of parents B.F., T.F., P.W. AND S.W., vs KETTLE MORAINE SCHOOL DISTRICT over improper social transition of their children in school. Please read it:
will-law.org/wp-content/uploads/2023/02/Expert-Affidavit-Stephen-Levine-2023.02.0333.pdf

Dr. Stephen Levine is a clinical psychiatrist and professor at Case Western Reserve University School of Medicine with decades of experience with gender dysphoria. Dr. Levine was the chairman of the committee that developed WPATH's SOC5 and was the court-appointed expert in the first major case in the country to reach a federal court of appeals about surgery for transgender prisoners."

👀

Don't get too excited. Cochrane reviews have extremely rigorous methodologies, and are very careful to assess risk of bias and only include well conducted trials.

I'd put money on the result being "no adequate trials found. More research needed."

Which isn't a bad result, but despite how often this happens, the well conducted trials still fail to appear.

Also wait for the howls and screams of transphoooobia when shitty trials are rejected. (cf reviews of various nutriceuticals over the years when they were told "your shitty trials are shit" but in more sciencey words).

I’m not sure that you can quantify/prove gender dysphoria, so how can you quantify outcomes?

it’s qualitative studies which will matter and there is already significant data to show that a very significant minority of people who have surgery are not happy afterwards.

I'd put money on the result being "no adequate trials found. More research needed."

Well yes we already know there’s no evidence but when the likes of Cochrane say there’s no evidence then surely clinicians will have to stop pretending that there is. Nice have said no evidence, Cass has said no evidence, Cochrane will also say no evidence and clinicians will have to come to terms with the fact that they are using children as guinea pigs.

This is any interesting development. I too wonder where it will go.

If in the review they analyse studies and papers that have been positioned as evidence in the past and write their analysis on why that study/paper is weak, that could be helpful.

i guess we watch and wait.

Yes. It's the kind of ground-zero we probably need to go back to in order to make sure that people are given good, evidenced care.

I suppose my concern is that that will give some the green flag to do more large scale trials.

During which some will continue prescribing it off licence because trials are happening.

It's an interesting experience slowly working through hrt levels and finally being offered testosterone which is off licence and also above the licensed oestrogen 100 dose. (I've had blood tests and long discussions.) Makes me realise how easily hcps started offering pbs at the Tavi because others were and more were asking for it.

Cochrane have a v robust methodology. If they deviate from it, it wil be vvvv obvious and will damage their credibility, so i think the risk of bias is small.

The v likely outcome will be, more research needed, but they can and do also highlight the potential harms of interventions. In a non life threatening condition evidence of possible harm does not need the same very robust levels of evidence as possible benefits.

They will give a steer on how to generate the evidence needed ethically. Which will not be easy.

This is good news and much needed, but is no silver bullet.

It will be a positive if they say there is not enough evidence either way to support puberty blockers as a medical intervention.

Agree, i do hope they include assement of potrlential harms in the term of reference for the review. I suspect this will be very damning.

”It will be a positive if they say there is not enough evidence either way to support puberty blockers as a medical intervention.”

It most certainly will be a positive.

Yes that's my hope too. I've read too many analyses of studies where one person is saying the study shows a positive outcome and another person is saying the exact same study shows a negative outcome. It would be great to have an independent analysis that is not linked to one "side" or the other.

In 2020 Cochrane did a systematic review on trans women taking hormones - https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013138.pub2/full.
The found "We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches (estradiol alone or in combination with cyproterone acetate or spironolactone) for transgender women in transition. The evidence is very incomplete, demonstrating a gap between current clinical practice and clinical research."

I think it's interesting that they point out the gap between clinical practice and the evidence base. And I think they'll probably say the same for a systematic review on puberty blockers. To be honest though, most Cochrane Review say more good quality evidence is needed.

A lot depends on the specifics of the research question (for example I think it's very likely that it will cover both effectiveness and safety, but in theory it could be only the forner), and how they define 'effective'.

Is it not duplication of the NICE reviews? Or is it meant for a US audience since they have brought in Steven Levine?

Cochrane isn’t US based. It’s UK based, named after Archie Cochrane. I think it would be just a different approach. NICE is very much about UK health funding decision making, although the rigour with which they analyse the evidence will be the same.

A Cochrane review is the definitive evidence to publish on Pubmed. It will be useful.

Although there’s already enough to say there’s no evidence and gender clinics and authorities ignore that. This will be just another thing for them to ignore.

The original tweet has been deleted though. So maybe premature from Genspect.

The original tweet has been deleted though. So maybe premature from Genspect.

Hadn't noticed that. They should really make a comment to say why it's been deleted rather than just delete.

As NotBad says, Cochrane will be looking at pretty much the same evidence base as NICE (although how the research question is phrased may mean some differences in inclusion/exclusion criteria for the literature search) but the focus will be different.

Cochrane is 'what does the evidence say' and NICE is 'on the basis of the evidence, what should the NHS do'. So Cochrane has a potentially wider scope.

That is, the same published literature evidence base. I think Cochrane doesn’t include less formal patient and expert testimony in the same way as NICE. So it's narrower from that point of view.

They should complement but not completely replicate each other.