Pharma funding 'made no difference'
Pharma funding 'made no difference'
A Dutch pioneer of puberty blockers joins the growing debate
One of the Dutch clinicians most closely involved in promoting the novel use of puberty blockers for transgender-identifying children has dismissed any suggestion of a conflict of interest arising from the Amsterdam clinic receiving funds from the pharmaceutical company that makes the drugs.
“I do not think we would have acted differently without the grant [from the Switzerland-based drug company Ferring],” the Dutch clinical psychologist Dr Peggy T. Cohen-Kettenis said in response to questions from GCN.
The “financial support” from Ferring Pharmaceuticals was disclosed in a key 2006 paper from the famous Amsterdam gender clinic setting out how to use hormone suppression drugs, known as gonadotropin-releasing hormone analogues (GnRHa), to block a trans patient’s unwanted puberty.
However, the potential influence of the Ferring grant has been raised recently amid more intense scrutiny of the late 1990s Dutch innovation of puberty blocker drugs for minors diagnosed with gender dysphoria, a distressing sense of conflict between an inner “gender identity” and biological sex.
Puberty blockers have been rapidly adopted by rich nations around the world since the mid-2000s, with exponential growth in gender medicine and the emergence since the mid-2010s of an atypical dysphoria caseload dominated by troubled teenage females.
Doco: The Detransition Diaries
Side effects v torment
In an opinion piece for the liberal Dutch newspaper NRC Handelsblad last December, journalist Jan Kuitenbrouwer and media sociologist Peter Vasterman reported that there were 1,600 minors in treatment at Dutch gender clinics in 2022 and another 1,800 on the waiting list.
They noted the Ferring grant acknowledged in the 2006 paper by Dr Cohen-Kettenis and paediatric endocrinologist Dr Henriette A. Delemarre-van de Waal which described the use of puberty blockers.
“Potential side effects were played down — they were [said to be] outweighed by the great benefits, consisting of relief from the torment called gender dysphoria,” the Kuitenbrouwer-Vasterman article said.
In 2011 and 2014 the Amsterdam clinic — now known as the Knowledge and Care Centre for Gender Dysphoria at the Amsterdam UMC university hospital centre — published two key papers claiming positive outcomes for puberty blockers, opposite-sex hormones and trans surgery. Dr Cohen-Kettenis was among the authors of both of these “Dutch protocol” papers.
The promise of relief from youth gender dysphoria led to widespread imitation of the Dutch protocol, although the Amsterdam clinic had expected clinics in other countries to do their own research.
The Kuitenbrouwer-Vasterman article suggested there might be bias in the fact that “almost all” the studies relied upon by the Amsterdam clinic “came from its own practitioners, so the researchers are simply evaluating their own work.
“Before the capacity of Dutch trans care is drastically expanded, existing care must be subjected to critical, independent evaluation.”
Their article called for immediate action by the Healthcare and Youth Inspectorate, a regulatory body that is part of the Netherlands Ministry of Health, Welfare and Sport.
In a reply article in NRC, Dutch clinicians said: “A climate where gender care, already overburdened with long waiting lists, has to be subjected to external critical evaluation and inspection is not helpful to [our young patients].”
Two recent studies have argued that the beneficial outcomes claimed in gender clinic research are hostage to potential bias and placebo effects.
The Ferring grant
Dr Cohen-Kettenis told GCN that her late colleague Dr Delemarre-van de Waal had asked Ferring “if they would be willing to pay for two junior research positions.”
She said work began on hormone suppression in the 1990s “because we saw the distress of gender incongruent youngsters and there were reasons to believe that puberty blocking treatment could greatly enhance their quality of life.
“However, because there were many open questions on the effects of this approach, we only wanted to do this after careful selection of the youngsters and while intensively monitoring the development of the adolescents.
“In case of any signs of negative effects [from hormone suppression] we would have ended the protocol.”
Hence the rationale for seeking money from Ferring was to monitor more closely the patients given puberty blockers at the Amsterdam clinic, she said.
Dr Cohen-Kettenis said Dr Delemarre-van de Waal, a paediatric endocrinologist, had been in contact with Ferring over previous studies, such as those involving the condition of precocious puberty, and had handled the financial arrangements for the puberty blocker grant.
“It was nice that we had some means to better monitor the development of the adolescents than would have been possible without extra support, but I do not think we would have acted differently without the grant,” said Dr Cohen-Kettenis, who retired a decade ago as head of the Amsterdam Center of Expertise on Gender Dysphoria, as the clinic was then known.
She did not respond to a question about the amount of funding that the Amsterdam clinic had received from Ferring or any other companies making drugs used in medicalised gender change for young people.
The 2006 paper — titled “Clinical management of gender identity disorder in adolescents: a protocol on psychological and paediatric endocrinology aspects” — was presented at an international paediatric endocrinology symposium, and Ferring supported publication of the proceedings. (Gender identity disorder has been replaced as a diagnosis by gender dysphoria.)
It is not uncommon for pharmaceutical companies to fund clinical research, although the wisdom of this practice is debated.
Grateful
The disclosure of the grant in the 2006 Dutch paper simply said: “The authors are very grateful to Ferring Pharmaceuticals for the financial support of studies on the treatment of adolescents with gender identity disorders.”
The paper recommended a careful approach to puberty blocking, saying: “It seems possible to select patients who will profit from early interventions, starting at 12 years with [puberty blockers] and followed at 16 years by cross-sex hormone treatment, provided that the diagnostic procedure is carried out with great care and by an experienced team.
“Since the diagnostic procedure is lengthy, there is ample time for patient, the family and the psychologist or psychiatrist to make the final decision [whether or not to go ahead with ‘sex reassignment’].
“Making a balanced decision on [sex reassignment] is far more difficult for adolescents who are denied medical treatment [puberty blockers included], because much of their energy will be absorbed by obtaining treatment rather than exploring in an open way whether [sex reassignment] actually is the treatment of choice for their gender problem.
“By starting with [blockers] their motivation for such exploration enhances, and no irreversible changes have taken place if, as a result of the psychotherapeutic interventions, they would decide that [sex-reassignment] is not what they need.”
The 2006 paper acknowledged that blockers might leave patients with low bone density and a high risk of osteoporosis, and said it was “not clear” what effect suppression of puberty might have on development of the adolescent brain.
There is growing international debate over the purpose, safety, reversibility and effects of puberty blockers, the quality of assessment leading to their prescription, and the competence of children as young as age 8-9 to give informed consent to this treatment.
Note: GCN sought comment from Ferring
The extraordinarily unscientific and irresponsible approach of some of these clinicians seen in their statements which could be summarised as: "We know it works because we say it works" and "We can't do any more research because kids are desperate for these treatments" is breathtaking.
Then there are the unsupportable rationalisations used to justify the study in the first place: "It seems possible to select patients who will profit from early interventions". On the basis of a mere possibility clinicians were willing to experiment on children in ways that (they should have been able to foresee) would foreclose their future development, sexual function and fertility?
Similarly gobsmacking is the unconvincing "trust us" style protestations such as: "In case of any signs of negative effects ... we would have ended the protocol". Given that the negative effects were and remain largely unknown (though it's becoming clearer there are multiple, severe negative effects) how could they possibly have been monitoring adequately for them? There's also a glaring absence of any acknowledgement by the researchers that these procedures were (and are) experimental.
Arguing that children won't be able to make a "balanced" decision if not given the treatments because all their energy will be focused on obtaining such treatment is like arguing that teenage heroin addicts should be given heroin because otherwise they'll just be distracted by the desperate search for supplies of it, so how could they possibly make their mind up about their future?
Then of course there's the now standard argument that blockers give kids "time" to make up their mind, which completely ignores the reality that by blocking puberty, clinicians are preventing kids from undergoing a natural developmental stage which in the vast majority of cases in itself assists in the resolution of gender dysphoria. As we know from Dr Ken Zucker's work, something like 88% of kids with GD came to accept their sex if allowed to go through puberty. Giving puberty blockers unavoidably inculcates a fear of puberty and a belief that it's "wrong" for the patient to undergo such an "horrific" process, rather than normalising it as a natural maturational process. It's no wonder that practically all kids on PBs progress on to wrong sex hormones. Administering PBs amounts to a determination that the child is "trans" or "non binary" and must therefore continue along on the trans treatment train.
To add fuel to the fire, most outrageously, for them to assert that they—in contrast to ordinary mortals throughout history—are incorruptible is an insult to our intelligence. Of course this seduction by the pharmaceutical industry is a problem throughout medicine but that does not excuse this absurd claim. Everyone is corruptible, and the corruption often occurs unconsciously. Studies have shown that doctors can be powerfully influenced by attractive female drug reps in skimpy outfits, and by gifts as insignificant as a pen with the name of a drug on it. Similarly, medicos' belief in a treatment (and arguably, warm fuzzy feelings about a generous pharmaceutical benefactor) can influence the patient's experience of treatments without the clinician needing to say a word about it. In other words, it's communicated through body language, tone of voice and facial expression, hence the need for "double blind trials". So suggesting that something as crucial and significant as funding researcher positions doesn't alter the results of studies beggars belief.
We need a return to the Watchful Waiting with psychotherapeutic support approach to gender dysphoria. People can follow us on: https://www.facebook.com/WatchfulWaitingOz
This whole area reminds me of a similar situation in my field of oncology.
In the late 80’s and 90’s High dose Chemotherapy with stem cell rescue was promoted as a treatment for Breast Cancer. It made sense. This treatment was successful in Testicular Cancer and Lymphoma. Why wouldn’t it be successful in Breast Cancer. However there was a lack of randomised studies until one was published by Dr Bezwoda in South Africa which was reported as highly positive. On the basis of this study Insurance Companies in the USA started to pay for the treatment.
Unfortunately after an audit of Bezwoda’s work in 1999 his study was found to be fraudulent. Subsequent randomised studies found no advantage for the treatment and substantial toxicity. The treatment was subsequently denied funding.
I do not suggest fraud in the Dutch studies but note the similar amount of enthusiasm by followers of the Dutch study for an unproven treatment and similar arguments against randomized studies.
And remember the Oncologists who were treating Breast Cancer were treating patients with a deadly disease.
In the case of gender dysphoric children we are treating physically normal children and putting them on a possible pathway of irreversible mutilating surgery.
I believe the only way these children should be treated is in a proper randomized placebo controlled trial. It may not be possible to blind the study completely.
Ethics Committees need to step up and demand that all ad hoc treatment cease until such trials show a benefit.