The Cass Review Into Gender Identity Services For Children - Part 5

Puberty blockers, bans, and the most contentious part of the review

May 19, 2024

This is part 5 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):

Arguably the most contentious - and most discussed - aspect of the Cass review is the impact it has had on treatments. If you talk to defenders of the review, it made the obvious, science-based call to limit - but NOT ban - puberty blockers for children because there’s no evidence that they work. If you ask the review’s detractors, the recommendations are banning effective therapies for children that we KNOW work, and will cost many lives.

I think both of these positions have some truth to them, but are also mostly wrong. The review did call for what is effectively an indefinite ban on puberty blockers for children in the UK. The strongest evidence that the review was able to identify did show that puberty blockers are associated with mental health benefits in the treatment of transgender children.

That being said, even the best evidence for puberty blockers wasn’t very good. Whether or not you think the decision to ban blockers was reasonable, it’s important to understand that the current data supporting them has serious flaws, and those flaws need to be remedied.

Let’s look at the data.

What Are Puberty Blockers?

Puberty blockers are a class of medication that basically stops people’s bodies from producing the hormones responsible for puberty. In children who are experiencing puberty symptoms - deepening of the voice, periods, etc - this acts to prevent further development.

Blockers were originally developed primarily to treat precocious puberty, which is a condition caused by a variety of factors that can make children undergo puberty at young ages. In most cases, this means around the age of 7, but for some children precocious puberty can start as young as 3 years old. Puberty blockers are given to these kids usually from when the condition is identified until they reach a normal age for the onset of puberty (around 10 years old).

For trans children, the idea behind puberty blockers is fairly simple - they are experiencing dysphoria that is caused by changes related to gender. If you pause those changes, using a tested method, then the kids can take some time to decide if they want to transition or not.

Myths and Misrepresentations

The first important thing to clear up is the question of whether the Cass review has recommended a ban on puberty blockers. This is what the review’s FAQ has to say:

“Is the Review recommending that puberty blockers should be banned?
No. Puberty blocker medications are used to address a number of different conditions. The Review has considered the evidence in relation to safety and efficacy (clinical benefit) of the medications for use in young people with gender incongruence/gender dysphoria.
The Review found that not enough is known about the longer-term impacts of puberty blockers for children and young people with gender incongruence to know whether they are safe or not, nor which children might benefit from their use.
Ahead of publication of the final report NHS England took the decision to stop the routine use of puberty blockers for gender incongruence / gender dysphoria in children. NHS England and National Institute for Health and Care Research (NIHR) are establishing a clinical trial to ensure the effects of puberty blockers can be safely monitored. Within this trial, puberty blockers will be available for children with gender incongruence/ dysphoria where there is clinical agreement that the individual may benefit from taking them.” (Cass review FAQ)

There are two arguments here - the review had nothing to do with the ban itself, and it’s not really a ban because there will be a trial looking at blockers that trans kids can take part in.

The first point is just an odd thing to say. NHS England cited the Cass review and/or its interim report in all of their discussion of their policy on blockers. While the review did not have any legislative powers to implement a change in policy, it’s obvious that the findings of the Cass review played a large part in the decision-making for puberty blockers in the UK.

As to whether this consists of a ban - it’s somewhat complex. It’s true that NHS England has started pulling together a research oversight board, who among other things will be looking into starting a randomized trial into puberty blockers. This board was announced in 2023, and is so far still looking for several members. NHS England has also announced a chief investigator into the study.

However, the NHS websites note that studies like this take a lot of time to plan. There are ethical considerations, funding has to be identified, etc. The labyrinthine processes of the notoriously inefficient NHS bureaucracy have to be carefully appeased, which may take months or even years.

There are some very important things missing from the current public NHS plans - notably, a timeline. It’s possible that the trial will start next month. Unlikely in the extreme, but possible. It’s also possible that the start date will be initially planned for mid-2026, and then the inevitable delays will creep in and we don’t see an actual study until well into the 2030s. Without firm, public commitments, it’s hard to even be sure that a trial will be run, never mind when it’s going to start.

In practice, this means that puberty blockers are banned for trans children through the NHS in England. When (if) the NHS finally gets around to running the study, children will be able to roll the dice as part of a randomized trial to maybe get blockers, as long as they are close to a trial site.

It is, in my opinion, incredibly misleading for the Cass review to argue that this does not constitute a ban. The review has argued that blockers are potentially unsafe, have no proven benefits, and should not be used outside of clinical trials which do not yet exist. This is underscored in Appendix 6, which is a letter from Dr. Cass to the NHS from 2022:

“If this is the case, brain maturation may be temporarily or permanently disrupted by puberty blockers, which could have significant impact on the ability to make complex risk-laden decisions, as well as possible longer-term neuropsychological consequences. To date, there has been very limited research on the short-, medium- or longer-term impact of pubertyblockers on neurocognitive development. In light of these critically important unanswered questions, I would suggest that consideration is given to the rapid establishment of the necessary research infrastructure to prospectively enrol young people being considered for hormone treatment into a formal research programme with adequate follow up into adulthood, with a more immediate focus on the questions regarding puberty blockers.” (Cass review, Appendix 6)

From a practical perspective, this is a ban, regardless of how the review’s FAQ chooses to term the policy impact of their recommendations. It’s also rather bizarre that the review would spread such obvious misinformation on their own website, given that pretty much everyone else understands that this is indeed a ban:

“The ex-president of the Royal College of Paediatrics and Child Health made clear her view, which NHS England had already adopted last month, that they [puberty blockers] should no longer be given to anyone under 18 on safety grounds.” (The Guardian)

Do Puberty Blockers Work?

On to the crux of the issue. The stated goal of puberty blockers is to pause puberty so children experiencing some measure of dysphoria can figure out what they want to do. Perhaps they want to go on to change their gender, but perhaps they would rather detransition and go back to however they identified before. Perhaps neither of these choices fits them, and they want to keep experimenting without going through an irreversible change in their bodies for a bit. The aim of this treatment is specifically to improve mental health by reducing dysphoria - ideally, by removing some of the identifiable gender markers like facial hair, breasts, or periods, and give children a chance to figure out who they want to be without the pressure of puberty.

There were two key issues identified by the Cass review in the use of puberty blockers in the UK. I think both of these concerns are entirely reasonable:

Extended use. The review found that it was not uncommon for people to be discharged to adult services while still on puberty blockers. This could mean anywhere from 3-10 years of use, at a minimum. The drugs were never really developed for such prolonged use in older teens.
Age of prescription. For children, these drugs have almost exclusively been tested in much younger ages. The average age for children to get puberty blockers in the NHS data was about 15 years. As the review notes, this is too late to be effective - many teens would be at the late stages of puberty, and there would be little benefit to taking blockers at all.

In addition to this background, there’s also a systematic review performed by the University of York. I’ve written about these reviews before, check my previous pieces for more information on exactly what they entail. This review basically found that the evidence supporting puberty blockers was extremely limited.

Specifically, the review found a total of 50 studies looking at the impacts of blockers on the health and wellbeing of young children. 24 of these studies were considered low-quality, mostly because they used arbitrarily-selected populations, had limited follow-up, no comparison group, or similar issues. I explained more about the term “low-quality” in a previous article, but in this context it basically means that we can’t use these studies to derive a convincing causal connection (i.e. we don’t know if puberty blockers caused any specific reported effects, or if it was just an association).

Of the rest of the research, quite a lot of it did not measure benefits for puberty blockers at all. A number of studies - for example, these two - looked at potential side-effects of puberty blockers without measuring mental health/dysphoria outcomes. Still other studies looked at whether puberty blockers were effective at suppressing puberty, without gathering data on how this impacted children’s health more broadly.

On the key question of whether puberty blockers improve, or at least prevent reductions in, mental health, the review found a worryingly small total of 6 studies*:

This cross-sectional paper measuring global executive functioning in trans children. The authors found that taking puberty blockers for a longer period of time was associated with a tiny increase in traits that are associated with autism.
This before/after study looking at trans kids at the Dutch gender clinic. This study formed the basis of puberty blocker treatment for many countries, as it shows that children given blockers improved on a range of measures (but with no control group).
This before/after study of 44 children who went to the UK gender clinics. The authors found no differences on any measure of mental health or broader wellbeing in these children after taking puberty blockers.
This large longitudinal study showing that puberty suppression in addition to psychological support was more effective for psychosocial health than psychological support only.
This before/after study showing no change on responses to an autism-related questionnaire when children were given puberty blockers, again with no control group.
This cross-sectional study. This study was the only one that the York authors rated as high-quality. The study compared children who had just been referred to a gender clinic with children who had been treated with puberty blockers and a general population control. The children who had not yet started treatment had very high rates of suicidal ideation, while those on puberty blockers had the same rates of reported suicidality as the control group.

This is, genuinely, a terrible state for the evidence to be in. There are no studies that use objective measures of mental health - such as emergency department presentation - to assess whether blockers effectively prevent serious issues. Half of the papers have no control group. The single best study - as rated by UYork - is, in my opinion, fairly weak. Comparing children at one timepoint on a self-rated scale is a useful thing to do, but it doesn’t provide robust evidence of a beneficial effect of blockers.

The best we can say, based on this evidence, is that there appear to be some benefits associated with puberty blockers for children who are referred to gender clinics, but that such benefits are quite uncertain. The best data suggests that puberty blockers improve mental health for trans kids, but it’s certainly not definitive.

As for the negative side-effects - the systematic review found that trans kids experience pretty much the same issues as cisgender children who take these drugs. They temporarily cause modest reductions in bone density, as well as mild and sometimes more severe headaches, and can cause some fatigue and mood swings. There may be some impact of puberty suppression on height and growth, but this is uncertain, and there’s also some evidence that the drugs can cause modest increases in body mass and decreases in muscle. Finally, there is evidence that puberty suppression reduces penile growth in trans girls and may make it harder for them to have vaginoplasty as adults. It is worth noting that most of these side-effects are supported by randomized trial data from studies in cis kids, so we do know that they are likely real issues.

Implications

What this data means for children who want to access puberty blockers is, as with many things, complex. The Cass review has taken arguably the most extreme position possible, and called for an indefinite blanket ban on blockers until such time as the NHS proves that they work, even extending this ban to private providers. But is this a reasonable thing to do?

One of the strangest parts of the Cass review is the speculation on the potential negatives that medications may have. For example:

“A further concern, already shared with NHS England (July 2022) (Appendix 6), is that adolescent sex hormone surges may trigger the opening of a critical period for experience-dependent rewiring of neural circuits underlying executive function (i.e. maturation of the part of the brain concerned with planning, decision making and judgement). If this is the case, brain maturation may be temporarily or permanently disrupted by the use of puberty blockers, which could have a significant impact on the young person’s ability to make complex risk-laden decisions, as well as having possible longer-term neuropsychological consequences.” (Cass review, page 178)

The review is here arguing that puberty blockers may cause permanent damage to the brains of trans children because pubertal hormones are essential for brain development. There are several bizarre aspects to this argument, not least that it would apply just as much to delaying ‘natural’ puberty in cisgender children with precocious puberty. If you look at the reference here, it first goes to appendix 6 of the review, which is a letter from Dr. Cass to the NHS. On the final page of that letter, Dr. Cass makes the same claim as appears in the final review, and references it to this 2017 perspective paper which discusses a series of experiments on hormone manipulation in rodents.

For a review that spends a great deal of time bemoaning the state of the evidence supporting transgender care, this is an astonishing thing to do. The cited reference is a speculative theory about the importance of pubertal hormones on mice, with no follow-up data in humans. The studies discussed in this short perspective do not even look at puberty blockers - because these studies were in mice, the researchers simply removed the animal’s gonads to prevent puberty and then gave some of them synthetic hormones.

In arguing for a ban on puberty blockers, the Cass review seems to put more weight onto this sort of bizarre and unsupported speculation than on the (admittedly poor) evidence that blockers may be beneficial. From a scientific perspective, it’s hard tos ee why short reviews of rodent research are even being referenced in the document, never mind given more space than studies on real children who received the medications in question.

It’s undoubtedly true that we need more, and better, research on puberty blockers. But it’s not clear at all that banning them indefinitely was the best way to achieve this. If the review had recommended that blockers only be banned the day that a huge, national study into the drugs started, I would have relatively few issues with the recommendation. You could even build this sort of study into the new clinical paradigm that the review also recommended, a hybrid evidence/implementation approach that is the sort of thing I do in my job as an epidemiologist. Instead, we’re left with a total ban and no end date in sight, with little assurance that the proposed trial will even be available for the entire UK.

You could also argue that all of this discussion is pointless. The benefits of blockers may be relatively poorly-understood, but the downsides are very well described. Some would argue that this should all just be a matter for children, parents, and their clinicians, and that any child who wants blockers, and whose parent is supportive and understands the risks, should be able to access them.

I don’t entirely agree with this stance, because we simply don’t understand the benefits very well. It’s possible that there may be no improvements** in mental health caused by puberty blockers at all. It’s not clear that you can ever have properly informed consent for a procedure where we simply don’t know all of the outcomes.

That being said, it’s clear that transgender health is treated differently than healthcare for cisgender children. There are many cases where a common medical practice had minimal evidence supporting it, and then subsequent randomized trials showing no benefit caused people to change their practice. That’s the story of knee arthroscopies for osteoarthritis, or Xigris for septic shock. It is, however, vanishingly rare for a regulator to step in to ban a common medical treatment based on no new evidence, but rather a worry that the existing evidence may not be strong enough. In some cases, even when we know a treatment doesn’t work, it is still in common use.

It’s hard to come to a final conclusion here. As with several parts of the Cass review, there are strengths and weaknesses. Some of the arguments about puberty blockers are correct, some are less correct, and some are unscientific speculation. At this point, we can only really look at the practical outcomes of the review - despite calling for more and better evidence, the main outcome of the Cass review so far is that children with gender dysphoria have fewer healthcare options than ever before.

*Note: There were an additional 3 studies that measured blockers to some extent but also included hormone therapy which were discussed in the review on hormones instead.

**Note: Preventing a decrease in mental health is also an improvement in this context.

Gideon M-K: Health Nerd

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