When sterility is the risk, placebo is far from harmless

Gender-affirming clinicians are testing irreversible treatments on people psychologically primed to report positive outcomes, argues Alison Clayton

This ecstatic post, published on a popular forum for transgender males, offers anecdotal evidence for a problem highlighted by Alison Clayton in a recent peer-reviewed letter published in Archives of Sexual Behaviour. Promoted by gender-affirming clinicians, treatments for gender dysphoria like puberty blockers, cross-sex hormones, and surgeries can create strong psychological reactions in vulnerable people, says Clayton, an Australian psychiatrist. 

Gender dysphoria is strongly associated with depression and anxiety, both of which are susceptible to the subjective effects of a placebo. She argues that the attention, the prestige of the clinician, and the promise of a cure are likely to boost people’s subjective measures of well-being.

Placebo effects refer to the beneficial effects attributable to the brain-mind response evoked by treatment context, rather than to the action, if any, of the treatment itself (“nocebo” effects are the negative effects). While it is commonly associated with the harmless “sugar pill” of double-blinded clinical trials, it can also refer to the imagined or perceived benefits of an active drug or treatment.

The partly-irreversible treatments that are part and parcel of gender-affirming care are far from consequence-free, argues Clayton, who is calling for debate on the subject. Apart from established risks like loss of fertility and decreased sexual function, there are also the understudied but highly suspected risks of osteoporosis and cognitive impairment.

With consequences like this, the evidence must be strong

Clayton told Genspect: “The research on puberty blockers and gender-affirming hormones that has been undertaken has not been able – and will not be able – to untangle the relative contribution of placebo effect versus specific effect in any found mental health changes. This is particularly important given the adverse risks associated with these treatments.”

“As I write in my letter, medical and surgical treatments given to vulnerable minors lead to life-long medicalisation, and hold the risk of serious irreversible adverse impacts such as sterility and impaired sexual function. Thus, we need strong evidence that they are as efficacious for critical mental health outcomes as claimed, and that there are no less harmful alternatives. As I argued, this area of medicine is a perfect storm environment for the placebo effect because of the enthusiastic promotion (unwarranted by the evidence base) by clinicians, celebrities, social media, and a denigration of other alternative treatment options).”

Fear of suicide is driving decision-making

Hormones and surgeries are often pitched by affirming doctors as preventatives for gender dysphoria’s highest-stakes outcome: suicide. Stella O’Malley, psychotherapist and director of Genspect, points out that the fear of suicide is inappropriately shaping clinical decisions, as unevidenced claims are often made in this arena. “The most comprehensive data available is from the Gender Identity Development Service (GIDS) at the Tavistock where between 2010 and 2020 there were 4 suicides out of the 15,000 children who were either attending GIDS or on the waiting list.” 

“While every suicide is a tragedy and we need to do everything we can to prevent it, these numbers do not suggest that this cohort is much more vulnerable to suicide than other cohorts of young people who are experiencing challenges to their mental health. Suicide is such a terribly frightening and devastating issue, and it is imperative that clinicians are informed by the facts and not by false claims. Mental health issues are complicated and simplifying them with a false solution does not help.”

Research and treatment, all at once

Clayton argues that affirming clinics are acting as both testing grounds for the efficacy of hormones and surgeries, while treating people with them, all at once. She argues: “(Gender affirming care) is being provided in a clinical environment that maximises the placebo effect. This is the same environment in which the same clinicians are researching (its) efficacy,” writes Clayton, adding, “while a placebo effect-enhancing environment may be appropriate for a clinical environment, it is far from an ideal treatment efficacy research environment….”

She goes on to describe the risks of combining expert opinion and low-quality evidence as a basis for medical interventions: “We have a population of vulnerable youth presenting with a condition, which has no objective diagnostic tests, and that is currently undergoing an unexplained rapid increase in prevalence and marked change in patient demographics.

“The treatment response is mainly based on patient-reported outcomes… Some clinicians, who may be affiliated with prestigious institutions, enthusiastically promote (gender-affirming treatments), including on the media, social media, and alongside celebrity patients.”

“Some make overstated claims about the strength of evidence and the certainty of benefits of (gender-affirming treatments), including an emphasis on their “life-saving” qualities, and under-acknowledge the risks. Alternative psychosocial treatment approaches are sometimes denigrated as harmful and unethical conversion practices or as “doing nothing.”

The letter has been praised by a critic of gender-affirming care, researcher and Manhattan Institute Fellow Leor Sapir, and called a “tour-de-force” by the Society of Evidence-Based Gender Medicine (SEGM).