The Cass Review Into Gender Identity Services For Children - Part 6

Does hormone therapy work for children with gender dysphoria?

Jun 14, 2024

Note: There’s been a bit of a delay on my Cass review pieces. It’s mostly because re-reading the document yet again makes me want to sandpaper various delicate parts of my anatomy. The final 3 pieces (including this one) are now on their way.

This is part 6 of my series looking at the Cass review into gender identity services for children in the UK. You can find the other parts here (I will update as I add sections):

The most contentious part of the Cass review into gender identity services for children is, by far, the discussion about treatment. The entire purpose of the review was initially to figure out what the best method for helping trans teenagers deal with their dysphoria is, and most of the controversial recommendations cover whether doctors should be prescribing drugs to teens with dysphoria.

We’ve already gone over the first major part of this - puberty blockers. If you haven’t read that piece, I would recommend going back and having a look. The discussion about hormones is not identical to puberty blockers, but they are closely linked.

So, hormone therapy. Where puberty blockers are broadly given to children to give them time to make a decision about their gender, hormones are a much more intentional intervention. Giving people cross-gender hormones - primarily oestrogen or testosterone depending on circumstance - is designed to dramatically and permanently change their gender presentation. Trans girls will grow breasts, trans boys’ voices will break, and generally the bodies of the people who take hormones will be forever modified.

What’s really interesting is that medically these drugs are actually much less divisive than puberty blockers. There’s reasonably good (if limited) data showing that hormones are an effective way to resolve gender dysphoria. This makes the Cass review’s decision to recommend a near-total ban on hormones very hard to understand.

Let’s look at the science.

The Background

The first thing that’s important to understand about cross-gender hormones is that unlike puberty blockers there is already some data showing that they work in adults. A 2021 systematic review - a type of study which aggregates together all of the research papers on a topic - found that the impact of cross-gender hormones was generally positive for transgender people. While the evidence was limited, and mostly observational, it did show that hormones generally seemed helpful for self-reported outcomes such as depression, anxiety, and quality of life.

There is also randomized clinical data showing that hormones improve self-perceived mental health for trans people. A 2023 trial randomized trans men and gender diverse people to either receive immediate testosterone injections or wait 3 months then get the treatment. This is a fairly standard waitlist control trial, and it showed that trans men who received testosterone reported improvements in mental health, wellbeing, dysphoria, and also said that they were much less likely to be suicidal than those who didn’t receive the hormones.

Now, even this study is limited. It was quite small, and again only looks at self-reported outcomes. However, it is the strongest evidence available on the question of whether hormones help trans adults, and it shows a clinically meaningful benefit. So what about transgender teens?

The Cass Review

Similar to puberty blockers, the main recommendation of the Cass review on the use of hormones for children with gender dysphoria was fairly simple: don’t use them. Specifically, the review recommended:

“NHS England should review the policy on masculinising/feminising hormones. The option to provide masculinising/feminising hormones from age 16 is available, but the Review would recommend extreme caution. There should be a clear clinical rationale for providing hormones at this stage rather than waiting until an individual reaches 18.” (Cass review, 197)

This is a fairly strong rejoinder against using hormones to transition gender in children. What was this advice based on?

As with most of the previous aspects of the Cass review, the recommendations were primarily based on a review conducted by York university. The review itself is quite similar to the one conducted on puberty blockers - the authors identified about 50 studies, most of which were relatively low-quality, with only one rated as high-quality by the team. There were five studies that considered the question of whether hormones improve the mental health of children, and the York team felt that most of them were quite small and not sufficiently robust to draw meaningful conclusions.

One interesting difference between the puberty blocker review and the hormone data is that essentially all of the data on hormones was positive. Every study that examined mental health outcomes of children given gender-affirming hormone treatment showed improvements. Specifically, these studies:

This large retrospective survey that found that the odds of recent depression and suicidality were lower in trans children who had been given access to gender-affirming hormones.
This small study comparing transgender boys receiving and not receiving hormonal therapy. Trans boys who were given hormones had lower rates of suicidality, and generally better mental health.
Another small prospective paper comparing trans children with cisgender controls from when they started hormone therapy to a year after starting treatment. After controlling for age, ethnicity, and socioeconomic status, the authors found that trans kids had much worse mental health before treatment than cis kids but that this was almost entirely resolved after a year on hormones.
A small before/after study on a group of trans kids who got treatment at a gender clinic, showing mental health improvements on a range of factors.
A very odd before/after study from Finland where researchers looked at a range of self-reported behaviors of transgender teens who were given hormones. The researchers ranked these behaviors according to their own opinions about what was important for young people (for example, not getting a job straight out of school was considered a reason for downgrading their wellbeing). Nevertheless, this small study found some benefits for mental health for teens who were given hormones.

These studies ranged in timeframe, but mostly looked at about a year on hormone therapy. Overall, on almost every measure, the data showed that hormone therapy for transgender teens was associated with improvements in mental health.

Both the York team and the Cass review’s interpretation of these findings is problematic. For example, the Cass review states:

“There were inconsistencies regarding suicidality and/or self-harm, with three of four studies reporting an improvement and one no change.” (Cass review, page 184)

This echoes the systematic review, which states:

“there were inconsistencies regarding suicidality and/or self-harm, with three of four studies reporting an improvement and one no change” (Taylor et al, 2024)

This is fairly straightforwardly false. Firstly, if 75% of your evidence shows one thing and a final paper is inconclusive, the literature is broadly consistent. In addition, the final paper, Grannis et al 2021 (number 2 on the above list), which both the York team and the Cass review says showed “no change” did in fact show a decrease in suicidality associated with hormones. Specifically, in transgender boys who received hormones, the average score on a self-harm questionnaire was 2, while in trans boys who didn’t get hormones it was 3.1. This difference was not statistically significant, with a p-value of 0.06.

In other words, the data is ENTIRELY consistent. Three studies showed a large decrease in suicidality, and one showed a large decrease that was not statistically significant. That is consistent with their being a benefit, it’s just not conclusive. This is also supported by two studies that were released after the systematic review were done, both of which also showed benefits for mental health associated with gender-affirming hormones. It is unclear why both the York and Cass review teams misrepresented the evidence in this case.

Overall, the systematic review seems to show positive, if limited, data supporting hormones as a treatment for gender dysphoria. While there are certainly weaknesses to the literature - only having seven studies in total looking at psychological wellbeing for the medications, most of them on very small samples, is not great - it’s generally quite positive about using gender-affirming hormones to treat gender dysphoria.

It’s also worth noting that the side-effects discussed in the review are quite modest. This is probably to be expected, because taking hormones such as testosterone have very well-understood costs and benefits. There are a few potential long-term issues for health - in particular, for trans girls hormones will impact fertility if given at a young age, and some potential implications for height, weight, and cardiovascular health as well - but these have been known about for decades. Guidelines for treatment of trans kids already emphasize the need to discuss the drawbacks of hormone therapy at length before starting it for this very reason.

So why did the Cass review recommend strongly against hormones? Well, there were a few other considerations that the review makes about the therapy. The review cites three papers from Denmark, Finland, and Australia to argue that bad mental health could be making children transgender, and that:

“Regardless of causality, the focus should be on treating all the young person’s needs, rather than expecting that hormone treatment alone will address longstanding mental ill health.” (Cass review, page 185)

This is quite a remarkable thing to argue. None of the studies included has any data which even remotely suggests that mental health issues can cause people to become trans. In addition, all of these studies show that trans children already get a lot of mental health treatment. In the Australian and Finnish studies, more than 70% of the children involved were seeing a mental health professional as part of their care. The Danish study did not measure this statistic, but it did still find that 29% of the included transgender people - in this case, mostly adults - had received a psychiatric diagnosis in their clinical records, and 25% were taking psychiatric medications.

The lack of mental health treatment for transgender children is a repeated concern throughout the Cass review, which is extremely strange. The data shows that most trans children already see a psychiatrist, psychologist, or other mental health professional. It is unclear which areas of mental health the authors of the review see as underserviced, and indeed what the authors think should be changed to prevent children from becoming trans.

In addition, the Cass review cites the aforementioned Finnish paper, stating that:

“Another recent paper (Ruuska, 2024), compared deaths by suicide in young people who had been seen in the Finnish national gender service with age-matched controls. The study also did not find a statistically significant link between hormone treatment and reduced risk of suicide. However, there was a statistically significant relationship between a high rate of co-occurring mental health difficulties and increased suicide.” (Cass review, page 187)

I’ve discussed this study before. In fact, the data presented shows a very large and statistically significant reduction in suicide risk for trans children who got treatment when compared to those who were not treated. The authors did not properly report this finding, but the entire purpose of the Cass review was to provide an objective scientific overview of the data. It is extremely problematic that instead the Cass review appears to have simply regurgitated scientific misrepresentations.

Finally, the review discusses detransition and long-term outcomes of hormone therapy. I’ve talked about this section of the review before, and why it is terrible.

To sum up, the reason for the Cass review suggesting a ban on all hormone therapy for teens appears to be:

The studies showing benefits for hormones are not sufficiently robust.
There are no proven benefits on suicide for trans teens who take hormones.
There are theoretical harms which are completely unproven and indeed extremely unlikely, but which must be given similar emphasis to the existing data in real children.

And thus, the recommendation that hormones should never - or almost never - be used in the treatment of trans teens until they reach the age of 18.

The Bottom Line

There seems to be a very strong pattern in the Cass review which we are seeing repeated in almost every part of the publication. First, we have a review of the evidence for gender-affirming care in kids. Mostly, the evidence isn’t great. This is an unfortunate fact, and one that I’ve discussed at length. Then, the review will cite various unsubstantiated theories that vary from possible to unlikely to complete pseudoscience. These theories are given equal - or in some cases, greater - weight than the existing evidence in actual trans children.

In this case, we have quite strong data showing that hormone therapy improves self-reported outcomes for transgender adults. There is also some evidence that such treatments are associated with reductions in suicidality and suicide for trans teens, although this evidence is not very good.

As with puberty blockers, it is definitely true that we need more, and better, research on hormone therapy for trans teens. There are numerous unanswered questions that the existing research is simply too weak to answer. It is again, however, not clear that the recommendation of the review is the best way to achieve this. Given the landscape of the evidence, most trans people will be able to access hormones as soon as they turn 18 - this is unlikely to change in the future. Most guidelines already recommend that hormones should only be started after 16. There’s no clear rationale as to why hormones should be delayed by two years given the evidence that the Cass review cites, and indeed there’s some reason to believe that allowing 16 and 17yos to access hormones could substantially improve their mental health.

This brings us to an important point about the Cass review and scientific evidence in general. Science deals almost exclusively with facts. Measurements. Data. We know that trans teens who were treated with hormones and blockers at a gender clinic in Finland were about 70% less likely to die by suicide than trans teens who didn’t get medical treatments. We know that trans boys have much worse self-reported mental health than their cisgender peers, but that this improves after they receive testosterone. We also know that the studies showing these associations have weaknesses which mean that we cannot necessarily say that the drugs caused the improvements in health and wellbeing.

What’s beyond science is telling us what we should do with this information. The authors of the Cass review believe that the data isn’t good enough to show a benefit, that there are possible harms, and therefore we should not use these therapies until someone does a series of high-quality studies proving that they work. But others could just as easily argue that the harms are theoretical but the benefits are demonstrable, and therefore to err on the side of caution we should make hormones more available because they so clearly work.

I don’t necessarily agree with either of these perspectives, but I would say that both have similar evidential support. Personally, I think that the data we have so far is more strongly supportive of gender-affirming care, but again this is just my opinion.

The point is that while the science shows what it does, the recommendation is entirely arbitrary. The Cass review authors could have decided to allow hormones for any child using clinical judgement, or recommended that the NHS immediately start trialing them in all trans children aged 16 and over, and been just as if not more justified as they were in arguing that hormones should almost never be used in this population.

As with puberty blockers, it’s hard to come to a final conclusion here. The existing data is weak, but it does seem to show that hormones may have large and clinically meaningful benefits for trans teens. We definitely do need better studies. Conversely, the arguments the Cass review presents against the use of hormones are extremely weak and often misleading. The Cass review’s discussion of detransition and regret is deeply flawed. All of this means that a final conclusion about using hormones for trans teens is hard to come by. Perhaps the most accurate thing we can say is that the Cass review’s recommendation to almost never use hormones for trans teens is clearly inconsistent with the evidence, but that it’s unclear what the best recommendation might be.