Review: ‘Evidence’ supporting puberty blockers ‘not reliable’

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Review: ‘Evidence’ supporting puberty blockers ‘not reliable’

An official review in the U.K. has found that evidence supporting the efficacy and safety of puberty blocking and cross-sex hormone drugs is of “very low certainty,” not reliable, and could be subject to conflicts of interest in favor of the drugs.

Last year, the National Health Service (NHS) in England called for a review into “gender identity services,” which is being led by Dr. Hilary Cass OBE, former president of the Royal College of Paediatrics and Child Health, and hence dubbed the Cass Review.

As part of the independent review, the National Institute for Health and Care Excellence (NICE) is also taking an active role, and has now released two reviews regarding puberty blocking drugs and cross sex hormones.

The first review examined a total of nine studies into “gonadotrophin releasing hormone (GnRH) analogues,” or puberty blockers, as well as cross-sex hormones. These examined the use of the drugs in comparison to other non-medical interventions offered to children who suffered from gender dysphoria.

Among other areas, NICE observed the effect of such drugs on children’s mental health, the psychosocial impact, the effect on bone density, cognitive development, “gender dysphoria,” and safety issues.

NICE found that these studies provided evidence which was not altogether trustworthy, and thus led to puberty blocking drugs being advocated on the grounds of inconclusive evidence: “The quality of evidence for these outcomes was assessed as very low certainty using modified GRADE.”

Another “key limitation” in determining both the “effectiveness and safety” of puberty blockers was a “lack of reliable comparative studies.” The studies had been completed and drawn up without proper control groups present, which would normally be used to compare and contrast results.

Additionally, there was a lack of “clear, expected outcomes” from using the drugs, which made “interpreting the evidence difficult.”

The nine studies forming the basis for the current review were “all small, uncontrolled observational studies, which are subject to bias and confounding, and all the results are of very low certainty using modified GRADE.”

All failed to properly report whether the children were suffering from any other physical or mental issues. NICE mentioned that this itself was “a possible confounder for the treatment outcomes,” since reported changes in outcomes could be due to “external care” rather than “psychological support” or the drugs themselves.

Hence the outcomes of using the drugs were not reported properly in “many” of the studies, with “relatively little interpretation of whether the changes in outcomes are clinically meaningful.”

In the instance of the correlation between bone density and puberty blockers, the studies were conducted in such a manner that they could not show “whether the findings are associated with GnRH analogues [puberty blockers] or due to changes over time.”

“All” of the studies dealign with bone density, and recording safety outcomes from the use of the drugs “provided very low certainty evidence,” stated NICE.

In a damning conclusion, NICE’s report wrote that results of the nine studies thus did not provide results which could be used as a trustworthy basis for use: “Studies that found differences in outcomes could represent changes that are either of questionable clinical value, or the studies themselves are not reliable and changes could be due to confounding, bias or chance.”

The report also alluded to possible conflicts of interest in the studies, in favor of puberty blocking drugs. Noting that the studies all originated from a small number of care facilities, mainly in Europe, NICE suggested that “the low number of services providing such care and publishing evidence may bias the results towards the outcomes in these services only and limit extrapolation.”

In revealing the poor science advocating for puberty blockers, NICE has vindicated the warnings made by advocates for many years.

NICE’s second review examined a total of ten studies, none of which “directly compared” the use of the cross-sex hormones to a control group.

“All the studies included in the evidence review are uncontrolled observational studies, which are subject to bias and confounding and were of very low certainty using modified GRADE. A fundamental limitation of all the uncontrolled studies included in this review is that any changes in scores from baseline to follow-up could be attributed to a regression-to-the mean.”

Similarly, “most” of the ten studies did not report any physical or mental health issues, and none reported accompanying treatments.

Hence, NICE wrote that “it is not clear whether any changes seen were due to gender-affirming hormones or other treatments the participants may have received.”

As with the puberty blockers, results from the cross-sex hormone studies actually suggested that they “may increase lumbar spine and femoral neck bone density,” although “not all results are statistically significant.”

Ultimately, NICE warned that the use of such treatment must be examined in light of the lack of proper evidence regarding its safety and efficacy.

The two reports closely mirror a report drawn up in 2019 by Professor Carl Heneghan, then editor-in-chief of the British Medical Journal (BMJ) Evidence Based Medicine, and Tom Jefferson, a tutor at Oxford University and a visiting professor at Newcastle University.

Examining similar outcomes, such as psychological effects and bone density, Heneghan and Jefferson pointed to “significant problems” in how evidence advocating the use of cross-sex hormones and puberty blockers had been collated and analyzed.

Pre-empting the NICE conclusion, the pair commented that the issues were so significant, that they precluded any “definitive conclusions” from being made.

“We are also ignorant of the long-term safety profiles of the different GAH regimens,” they wrote. “The current evidence base does not support informed decision making and safe practice in children.”

The Gender Identity Development Service (GIDS) for Children and Adolescents in the U.K. is managed by the Tavistock and Portman NHS Foundation Trust, which has come into increased scrutiny over the last several months, due to the court case of Keira Bell. Now 23, Bell had begun taking “puberty blockers when she was 16, was injected with testosterone at 17 and had a mastectomy aged 20.”

Currently “transitioning back to a woman,” Bell described how “she was treated like a ‘guinea pig’ at the clinic, and said doctors failed to carry out a proper psychiatric assessment and should have challenged her more over her decision to transition to a male as a teenager.”

As a result of her experience, the English High Court of Justice ruled that children under 16 were too young to understand and consent to puberty blockers, and that the drugs generally cannot be given to children attempting to “transition” to become a member of the opposite sex, without the clinician having recourse to the courts.

Tavistock itself has been recently handed the lowest rating possible by the U.K.’s Care Quality Commission, who labeled GIDS “inadequate” in January of this year.

 

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