Puberty blockers a 'safe, effective and reversible' form of gender-affirming care, finds review triggered by Westmead Hospital investigation

An independent review commissioned by the NSW government in the wake of a Four Corners story into gender-affirming care for children has found that puberty suppression treatment is still "safe, effective and reversible" but calls for more long-term quality research, acknowledging the strength of evidence is low.

The NSW government commissioned the report by the Sax Institute in the wake of a Four Corners report into gender-affirming care and a growing dispute among some clinicians in NSW about what was best for children with gender issues, as a polarising and sometimes toxic debate over the gender "affirmation" model plays out around the world.

Gender-affirming care can include puberty blockers to suppress puberty for young people distressed by their changing body. In some cases, this is followed by cross-sex hormones to change people's bodies to align with their gender.

A Four Corners investigation into Westmead Children's Hospital's troubled gender clinic revealed it had only seen three new patients as of July last year and was struggling to operate in the wake of a string of staff resignations linked to the publication of controversial research endorsed by the hospital hierarchy.

The paper, published in 2021, found there were "high rates of adverse childhood experiences including family conflict, parental mental illness and loss of important figures via separation" among a sample of 79 children who sought help at the hospital's gender service.

Perhaps most controversially, more recent research conducted at the hospital found gender-related distress was "resolved" or "disappeared" for 22 per cent of those who presented at the clinic.

The new Sax Report — which studies the quality of all the research — says that studies examining the characteristics of transgender and gender-diverse young people in Australia are limited to descriptions of those attending a Melbourne-based gender-affirming care clinic, concluding that "knowledge of characteristics of cohorts in other Australian jurisdictions remains limited to poor".

"The evidence base was dominated by studies without control or reference group comparisons. This limitation was compounded by the complex nature of gender-affirming models of care for people experiencing gender dysphoria, which may involve multifaceted interventions that are often concurrent and/or delivered over a long period of time. This makes evaluation of specific treatment effects for individual therapies challenging."

The report says the gap remains (as previously identified) for proof of effectiveness of the discrete interventions, medical or psychosocial.

While it is acknowledged that ethical limitations preclude the conduct of randomised controlled trials for many gender dysphoria interventions, "further comparative studies (i.e. Level III-2 and III-3 designs) would be of more value than uncontrolled (Level IV) studies in addressing this gap".

But the Sax review — which looked at 82 eligible studies into a broad range of gender-related interventions for young people — said it represented a considerable increase in the volume of research examining gender dysphoria interventions from 2019–2023, with only 46 studies eligible for the previous review covering the years 2000–2019.

But they found that "overall, the evidence about gender dysphoria interventions remains weak due to poor study designs, low participant numbers and single-centre recruitment".

The Evidence Check report, commissioned by the NSW Ministry of Health through the Sax Institute, provides a comprehensive update of research evidence on interventions for young people aged under 18 experiencing gender dysphoria and published between 2019 and 2023.

The Sax Institute identified 17 studies pertaining to puberty suppression treatment (PS) in the Evidence Check update and said "broadly, the newly identified evidence reinforced the finding of the previous Evidence Check regarding benefits and effectiveness. That is, PS agents … were reported to be safe, effective and reversible".

They found that in regard to risks and potential harms, reductions in bone density remain the primary concern with puberty suppressants and monitoring of bone mineral density is recommended.

They did, however, add a "qualification that the strength of the evidence remains low".

The report concludes that there are also a number of studies providing new evidence pertaining to the psychological benefits of hormone treatment, which includes things like testosterone to help people change their bodies.

"The identified studies reported positive results across the domains of body image, gender dysphoria, depression, anxiety, suicide risk, quality of life and cognitive function.

"However, neutral and some negative findings were also reported in these domains. Additionally, two Level IV studies reported no changes in mental health care use following gender-affirming pharmaceutical care.

"Although studies reporting positive mental health outcomes following GAHT (gender affirming hormone treatment) outnumber those with neutral or negative findings, considerable flaws remain in the evidence because of generally low participation rates of target groups, inadequate representation of young people and/or poor study designs and conduct."

The Sax Review update identified eight studies evaluating surgery for young people including one systematic review, with the updated evidence reporting generally positive findings for gender dysphoria, psychosocial outcomes and sexual function and quality of life.

However, there were neutral findings on psychosocial outcomes in transgender men as well as mixed positive/negative findings on quality of life.

The report finds that the "irreversible nature of surgery remains a key risk/potential harm, although regret rates were low where reported".

"Complication rates for chest surgery were also reported to be low. In contrast with the previous review, several studies reported on outcomes in adolescents referred for chest surgery at 16–17 years of age.

"Findings were generally positive across these studies on sexual function, gender incongruence and chest dysphoria. One Level I study reported low regret rates and two Level III-2 studies reported low complication rates.

"Although the evidence base is expanded and generally supports chest surgery, confidence in findings is low because of a lack of studies and/or poor study quality, use of mixed surgery populations and the confounding effect of hormone and other therapies, which almost always precede surgery."

Offsetting these limitations are three high-quality comparative studies with positive findings specific to adolescents.

In summary, this update provides some additional evidence that supports chest surgery: "However, further studies are required that focus on the effect of surgery in adolescents."

The new Evidence Check update has added "considerably" to the volume of evidence evaluating psychosocial interventions such as psychotherapy, family therapy and mental health/crisis support which are often pushed as alternatives to gender-affirming care by some who oppose physical interventions.

The previous review identified only three studies, with one a single case study: this Evidence Check has identified three systematic reviews and four primary studies including a randomised controlled trial.

The newly identified studies report benefits and effectiveness across numerous outcome domains including suicidal ideation, psychological distress, depression, anxiety and gender minority stress.

"Furthermore, most studies report that interventions are both acceptable and safe, with no risks or potential harms reported. Although the existence of an RCT is unique to this intervention category, it should be noted it was of a mixed population of sexual and gender-minority youth — the number of people experiencing gender dysphoria is not reported and no subgroup analysis of this group is presented."

They also warn that considerable limitations were identified in this body of literature.

In addition to the previously observed limitations of small sample sizes and lack of diversity in participant cohorts, these included a large number of psychological interventions with additional variability in delivery mode, and studies of mixed populations with no subgroup analysis of adolescents and/or transgender participants.

"Therefore, although study designs are stronger relative to other intervention areas in this Evidence Check update, a number of limitations that are applicable to studies of psychological therapies should be borne in mind when interpreting findings of studies of psychological interventions."