Excellent analysis of the PATHWAYS trial:
https://www.quackometer.net/blog/2025/11/pathways-a-trial-built-on-missing-data-pseudoscience-and-quiet-cruelty.html
'The trial’s design guarantees we will learn almost nothing useful about puberty blockers themselves. Every single child (treatment arm and delayed arm) receives the same new package of psychosocial support: therapy, family work, psycho-education, regular clinic visits, the full comforting apparatus of being “in the system”. The only variable that changes is whether a child receives triptorelin injections now or in twelve months’ time.
That single difference in treatment timing is the sole thread we have to pull on if we want to isolate the specific effect of the drug. Yet the thread is buried under a dozen powerful confounders: the therapeutic alliance, the placebo effect of finally being believed, the nocebo effect in the delayed group who feel cruelly denied, the natural maturation that happens to every teenager over two years, regression to the mean, and the simple passage of time away from whatever acute crisis brought them to clinic in the first place.
Because the psychosocial support is constant and the drug is the only thing that moves, any observed change in mood, self-harm, or quality-of-life scores can be attributed to the counselling just as plausibly as to the hormone suppression. The trial has no mechanism for disentangling the two. It is rather like testing a new analgesic by giving every patient in the study the drugs and a daily massage and then wondering why both the drug group and the waiting-list group report less pain. The protocol may produce reams of numbers, but it is structurally incapable of telling us what the blockers actually do.
Any improvement in quality-of-life scores can therefore be attributed to the counselling, to placebo effects, to regression to the mean, or simply to the relief of finally being taken seriously. We will never know which. The delayed arm, meanwhile, starts the study believing they have been denied life-saving treatment. Nocebo effects and off-protocol self-sourcing of blockers are inevitable. The trial cannot separate these confounders any more than a non-blinded homeopathy trial can separate the effects of sugar pills from the therapist’s reassuring smile.
The follow-up in the trial is just two years. Yet, the major questions are about what happens to children as they mature into young adults and further. Peak bone mass is not reached until the late twenties. Fertility outcomes, late cognitive effects, and long-term cancer risks will remain unknown. The promise of “registry linkage pending further funding” is not a plan; it is an admission that the most important clinical questions have been postponed indefinitely.
Picture a 12-year-old girl who starts blockers under PATHWAYS this winter. By the time she is 30 she may never know what an orgasm feels like and will certainly never carry a pregnancy. That is not a rare side-effect from what we know already; it is the intended physiological outcome of the treatment this 12 year old is being invited to “consent” to.
A majority of the children in such clinics arrive with autism, histories of trauma, depression, or eating disorders. Almost all cannot yet imagine adult sexual relationships or parenthood. To ask them to consent to a pathway that carries a substantial risk of permanent infertility and anorgasmia is to ask them to consent to something they cannot meaningfully understand. The consent forms may be legally watertight; they are ethically threadbare.'
...
If PATHWAYS had been submitted to the Cass Review as one more observational study it would have been graded low quality and filed under “inconclusive”. Instead it has been granted the status of the definitive trial, the one that will finally settle the matter. It will do no such thing. At best it will generate numbers that can be spun either way. At worst it will provide a veneer of scientific respectability for continuing to offer puberty suppression to children on the basis of ideology rather than science and evidence.'