Jamie Poisson (3:25)

And just to be clear, the hormone suppression is reversible.

Azin Goreshi (3:29)

Yes. That is like everything in this space, that word reversible is contentious. And we can get into why. I mean, the use with. For kids who are questioning their gender who identify as trans, the thinking behind how this is a useful treatment is that a, it stops physical changes that, you know, obviously the physical changes of puberty are themselves irreversible. So if someone is trans and they are a natal boy, but they, you know, identify as a trans girl, then going through the changes that, you know, growing a beard, shooting up in height, you know, developing broad bone structure, those are changes that will be with them for the rest of their lives. And pausing that puberty and allowing the child, you know, later on in teenage years to potentially start on hormones and transition basically prevents those changes from happening. The other thinking behind how it might be useful is that, as you said, if you do go off puberty blockers, you do resume puberty. So they have been sort of thought about as offering time to think, sort of time and space without the changes happening, for a young person to evaluate whether going down a medical pathway and continuing to transition is the right thing for them.

Jamie Poisson (4:50)

Yeah, yeah. And just to be clear here, we're gonna be spending the bulk of our time talking about puberty blockers today, not about the gender affirming hormone therapy which you mentioned. Yeah. Which is used to make physical changes in the body, not just used to pause puberty.

Azin Goreshi (5:07)

Right. Yeah. But the thing is that you can't totally separate them because, for example, if you start on puberty blockers at the start of puberty and then you continue on to hormone treatment, kids are at risk of losing their fertility. So if they don't continue on to hormones, that is not the case. So because it is a treatment pathway way, it is hard in some ways to, you know, totally untangle these interventions from each other because they are used sequentially in a certain way that has. Comes with the effects that, you know, make it different from using these drugs to treat something like precocious puberty, for example.

Jamie Poisson (6:04)

The blockers themselves, what questions are there around their use and safety?

Azin Goreshi (6:11)

These puberty blockers were first used to treat gender questioning adolescents in the Netherlands. And that work really started in the late 80s. It really picked up in the 90s and 2000s. And they saw at the Dutch clinic in Amsterdam, they saw that there was a small group of kids that, you know, from a very, very young age had had like a very, very clear and consistent cross gender identification. So the Dutch really pioneered this treatment. They published their first data on the first 70 kids that they studied who they treated with puberty blockers and then hormones in 2011. And that study found that after two years of being on puberty, they saw that the adolescents in their cohort were doing better psychologically, that there was an improvement in their well being. And that was a really promising finding. You know, this was a totally new use for this drug. And their approach was called the Dutch protocol, began to spread across the world starting in the sort of early to mid 2010s. From the very beginning, the Dutch had acknowledged that there were questions about using these drugs in this way that that made them different from the precocious puberty kids that we were talking about. You know, puberty is a time of rapid growth, as everyone knows. You know, bone density increases a lot during puberty, for example. And there were questions about, you know, if you pause that puberty, if you then continue on to hormones, what, what happens to a child's bone density? Do they, do they recover that? And those studies are really on, I mentioned this earlier, but there are also questions about fertility. There are open questions about brain development. You know, there's obviously puberty. That period is a time of just rapid change more generally and sort of emotional and cognitive development more generally. So there are questions about, you know, what happens if you interrupt this period. But I think the broader question hanging over all of this has been, is this the right approach at all? And sort of baked into that concern are questions about, you know, can adolescents know something like this about themselves? Can they make these medical choices and understand the consequences that might come down the line? And is there the possibility of possibly regret or detransition? I think that is the biggest sort of concern when people are talking about this treatment. Is, is it even the right treatment? And I think some of those concerns have gotten a lot more pronounced in the last decade since these gender clinics started to open worldwide, because we also started to see a really big change in the actual patient population that was seeking these treatments, we were seeing, you know, an increase in demand, a very steep increase in demand across a lot of these countries, including the US and Canada. And then there were concerns too about just the mental health. You know, the Dutch group was very specific in saying these are kids who had to have identified with the other gender, you know, from a very young age and couldn't have other co occurring psychiatric issues that were, you know, that were serious and could interfere with treatment. And we have seen that change a lot over the last decade as well. We're seeing a lot more adolescents and teens who are, you know, have identified as trans more recently and didn't have this sort of clear presentation from early childhood. And we're also seeing a lot more co occurring psychiatric issues and neurodevelopmental issues like autism. So those overarching questions about this as a treatment have, have gotten a lot more pronounced and have gotten a lot more serious, including among physicians in this field of medicine because the patient group has changed so much.

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CBC Announcer (11:04)

Of the Debaters, the show where Canada's funniest arguers battle it out. Are you one of the last people you know to still use a landline phone? This week we're asking if every home should have one and I promise we won't be phoning it in. Listen, wherever you get your podcasts, in.

Jamie Poisson (11:17)

The UK in particular, there was this big scientific review of gender identity services that was conducted by Dr. Hilary Cass. Right, the Cass review. And tell me what, what did that review find?

Azin Goreshi (11:35)

It was a very long report and it, it took I think four years for that group to put together. But at the center of the review were really these set of systematic reviews of the evidence to support this care. So she did different reviews for blockers, hormones, et cetera. The point of a systematic review is to basically pool all of the scientific studies examining a certain question, a certain intervention, sort of rate the strengths of those studies and then attempt to synthesize the entirety of the scientific literature and the Studies on a given question. And so what those reviews, which actually weren't done by Hilary Cass group, they were done by the University of York. They found that there was basically low quality evidence, I think Hilary Cass used the word remarkably weak evidence in support of this care. And I can talk to you a little bit about what that means. I mean, the way they sort of rate these studies is, you know, at the very top of the sort of study pyramid are randomized controlled trials. Those are the gold standard of science where you can, you know, give one group an intervention, give another very similar looking group, don't give them the intervention, basically compare the outcomes between those two groups. They have not been done in this field. So instead what we have are majority observational trials which just sort of follow a group of kids and report their outcomes. And you don't have that sort of highly controlled environment and you don't have clear comparison groups in the same way that you do in an rct. So those are automatically ranked as much weaker trials. But there were other issues with that they identified with the studies in this field, which is that, you know, these are often very small studies, which is perhaps not surprising. These are, this is ultimately still a very small group of kids. You know, the follow up, for example, was often not for a very long time. A lot of it boils down to the methodology behind the studies themselves. And the takeaway from the studies was that the evidence to support these treatments was weak. And so the CAST review was much broader than that. A lot of it got into how the actual NHS gender service itself was run. But I think the broader points it made about the quality of evidence in this space and sort of the concerns that we were just talking about, about long term risks and, you know, the, the changing patient population, for example, those kind of cut across, you know, all the different countries that have been sort of wrestling with this issue. Which is, I think why it had such a broad and, you know, pretty impactful. Why it had such a broad impact in the end was these are issues that we have seen being raised in different ways across the world.

Jamie Poisson (14:43)

And is it fair for me to say that as much as there was little evidence of the benefits of blockers, it also could find little evidence of the risks.

Azin Goreshi (14:55)

Yes, I think that's absolutely the case. I think, and I think that's something that Hilary Kass identified as actually a problem, was the field hadn't done. There wasn't enough research that had been done on, for example, bone density, those impacts around the fertility questions. A big problem is that there isn't more of a body of research on detransition, specifically in this community of younger people that have transitioned over the last 10 years. Something that, that Cass makes very clear in the report is that, you know, the way that the evidence is being interpreted by both supporters and people who are opposed to this care, that they are, both sides are sort of speaking with much too much certainty about what the evidence says. Like you have both the supporters of the care saying that this, this care is life saving, but you also absolutely have people who are opposed to this care pointing at the same evidence and saying, you know, it is, it is far too risky. We know you know, that this is, these are treatments that cause harm. And she is very clear in her report saying that we actually just don't know because the evidence is just so weak all around.

Jamie Poisson (16:13)

Like she never recommends a ban on gender affirming care and she explicitly says that for some it, it is the best outcome is transition. Right?

Azin Goreshi (16:23)

Yes. And I think the problem that she identifies is that because there is so little evidence in this space that it is, it is difficult to know which kids are going to be the ones that benefit. And that's a really big question, you know, for clinicians who are, who are treating this group is, is how do you know who, who will, you know, benefit long term from an intervention like this? The Cash report has sort of taken on a life of its own where people will use it to make whatever claim they sort of already want to argue. And I think she's pretty circumspect on that. She's very careful to say that this does benefit some, some young people. And she, you know, she specifically spoke with a very broad pool of people, both those who had, you know, this was something that was really important and very positive in their lives and people for whom, you know, there were, there were problems as a result of these treatments.

Unidentified Interviewee (Young Adult) (17:30)

I've spoken to young adults who've had very successful medical transition and are really thriving. I have also spoken to young adults who perhaps regret their decision. But I think what I found very distressing really is the people who are just sitting on a waiting list not knowing what's going to happen to them.

Jamie Poisson (18:10)

And so there are material impacts to this report when it drops. And just take me through those now.

Azin Goreshi (18:15)

Yeah, I mean, I obviously the most, the clearest impacts were in the uk. I mean, you mentioned in the intro that last year they announced a total ban on these treatments outside of the clinical trial that is now finally being launched.

UK Government Official (18:33)

I am acting on the Commission's advice to put an indefinite order in place to restrict the sale or supply of puberty blockers through a prescription issued by either a private UK prescriber or a prescriber registered outside the UK for under 18s. I know it won't feel like it based on the decisions I'm taking today, but I really do care about this and so does this government. I'm determined to improve the quality of care and access to health care for all trans people.

Azin Goreshi (19:04)

But the CAST report absolutely was, you know, noticed across the world. I think, you know, it was brought up certainly here in the United States. It was brought up in, you know, state legislatures. It was brought up in, you know, medical board meetings. It was brought up by our, you know, Supreme Court on several occasions in the ruling that they just made on the state bans.

Supreme Court Narrator (19:30)

Here, the Supreme Court is upholding Tennessee's ban on gender affirming care for transgender minors. In a 6, 3 decision today, the justices ruled that the state's law, which prevents children from accessing treatments like puberty blockers or hormone therapy, did not violate the Constitution's equal protection clause.

Azin Goreshi (19:49)

So it has absolutely been a really, really impactful document and I'm sure we're going to get to this. It's obviously also been very divisive, I think, as a result of that, you know, extremely broad impact that it's had.

Jamie Poisson (20:05)

Well, let me ask you about a critique of Dr. Kass's findings done by a number of doctors at Yale University, for example, and they believe that the reviews bar for evaluating research was set too high, that even though many studies do show the benefits of puberty blockers on minors with gender dysphoria, that they were dismissed as being of low quality by the CAS review. And just talk to me about that argument that those doctors at Yale are making.

Azin Goreshi (20:35)

The CAST report was not the first to conduct a systematic review like this and find low quality of evidence. We had already, by the time the CAST review came out, there had already been multiple countries in Scandinavia that had reviewed this evidence and decided essentially to sort of restrict, not ban, but restrict these treatments. Given the fact that there were questions about the evidence and there were, you know, these, these questions that we've been discussing around long term impacts, the designation of low quality, I think that this was a point made in that Yale report is something that is, it is technical. It is, you know, language that is used in the context of these systematic reviews that maybe translates differently, I think, if people are talking about it colloquially. But they did find this low Quality of evidence. We do see in other areas of pediatric care that there is limited evidence for the long term impact of drugs. And people bring up examples of drugs such as psychiatric drugs, that a lot of young people, especially since COVID have been put on. We were talking about randomized controlled trials earlier. It's difficult to do those in pediatric populations and, you know, evidence from adult populations is often used to then inform how to treat kids. I think this space has a number of issues that make it sort of unique in that, you know, these are drugs with a potentially, you know, irreversible long term impact. And so I think that also changes some of the sort of calculus around how to balance the risks and benefits.

Jamie Poisson (22:36)

So I think this brings us now to this new trial that I mentioned earlier, right, that they are about to embark on in the UK to look at the effects of puberty blockers for patients under 16. Around 220 young people will be recruited. And so how different is this from the studies that we've seen before? How significant is this trial? What kind of answers are people hoping for here?

Azin Goreshi (23:06)

It is different. Without getting too much into the weeds, the Dutch research that I was talking about earlier really is the sort of strongest evidence that we still have in this field. And there have been two sort of bigger studies that have attempted to sort of replicate the Dutch finding that found that after two years on blockers there were these increases in psychological well being and they found different results. One study in the UK found that there was no change after two years and they found that actually a third of the kids ended up doing better, a third of the kids ended up doing worse after the prescribed study period. Another study in the US also found no change. So there's a question about what might have changed since that Dutch research was first started. I think there, there will be a lot of scrutiny of this, of this new study to see, you know, what we can figure out about these subgroups, like who are these different groups of kids and why might they respond differently to this treatment? What does that say about maybe who the treatment is right for and who it's not right for? There's already been a lot of pushback to the trial being done at all. And, and that pushback has come sort of from both sides of the aisle. I think there were some letters sent out by Conservative MPs in the UK last week, sort of pushing back, saying that, you know, it's, it's unethical to provide puberty blockers to kids given what we know about them at this point. And Then on the other side, you have, you know, it is. It is unethical to say that the only way you can get access to these medications is by enrolling in this trial.

Jamie Poisson (25:03)

Right.

Azin Goreshi (25:04)

So it's. They're under a tremendous amount of scrutiny. I think they're also doing an observational trial with a much bigger group of kids alongside the trial that you mentioned. So I think there will be a lot more data, you know, certainly for the UK but also elsewhere for people to sort of evaluate some of these questions. And they. And they are specifically getting into both the psychological and the physical impacts that we were talking about.

Jamie Poisson (25:31)

Azine. I don't want to make you repeat yourself too much here, but I think it might be helpful for me to just ask you, as a final question, this straight. We have seen so many medical associations reiterate how medical evidence that politics should inform treatment decisions for trans youth. But as you've talked about, what makes this issue so challenging is that there are also a lot of questions and debate about the medical evidence itself. And I just. As a science reporter, what do you think is the most needed in the conversations that we're having about the use of puberty blockers in minors?

Azin Goreshi (26:12)

Yeah, I mean, I think that we need to really be hewing closely to what the studies have actually shown and getting into the sort of nitty gritty of, you know, the studies that have been done to date have found about both the benefits and the risks and be very candid about what they have not shown and the questions that still remain. I think, you know, it's really difficult in, you know, in the United States, we now have a situation where, you know, half the states in the country are banning these treatments outright.

Jamie Poisson (26:57)

Texas now the largest state to block.

CBC Announcer (27:00)

Gender affirming care for transgender children.

West Virginia Trans Coalition Protester (27:02)

More than 100 protesters gathered inside the West Virginia Capitol building supporting the West Virginia Trans Coalition, shouting shame on you as lawmakers. Entertainment the chambers as House Bill 2007 advances in the Senate. LGBTQ advocates are concerned for the health and well being of transgender youth because.

Jamie Poisson (27:22)

Of the legislative attacks that have been.

UK Government Official (27:24)

Pushed from this body and throughout this.

Azin Goreshi (27:27)

Country since President Trump took office. He has also made clear that even hospitals in blue states are at risk of losing federal funding if they continue to provide these treatments. So we're seeing hospitals actually independently make the decision that. That they can't risk that and shutting down these clinics. I think that, you know, something I've heard from clinicians and families, even those who are concerned about these treatments, is that shutting those things down will not help us get answers to all of these questions that everyone so badly wants the answers to. So I think that's another reason to be really watching what's happening right now in the UK really closely is that they have really invested in attempting to get answers to these questions because they recognize that they need to provide those to families. Like, families right now are getting a lot of very conflicting information, and it's very hard for them to make choices about what's best for their kids in that environment. And in the United States, when you. You know, we have people who are moving states and then moving to a state where maybe the hospital that they were planning on going to is also shutting down their clinics. So there's just. They're really. The families are really caught in the middle of this. And I think getting more data and for reporters, really reporting on what that data shows is really important.

Jamie Poisson (28:53)

Azine, that's a really good place, I think, for us to end. Thank you. This was really, really interesting. Thank you so much.

Azin Goreshi (28:59)

Awesome. Thank you so much for having me.

Jamie Poisson (29:10)

All right, that's all for today. I'm Jamie Poisson. Thanks so much for listening.

CBC Announcer (29:25)

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