Think hard

Dr Hilary Cass warns girls it's difficult to come back from testosterone

Photo by Simeon Jacobson on Unsplash

British paediatrician Hilary Cass has a warning for distressed girls considering testosterone: taking this powerful hormone will make it hard—in some ways harder than mastectomy—to pass as a woman if they end up regretting medicalised gender change.

“I hate to say this, because I’ll get all sorts of kick back, but testosterone is a more effective hormone than oestrogen in this context [as a cross-sex hormone],” Dr Cass said during a July 2 webinar on the implications of her landmark report for Australia.¹

“It is much easier to masculinise a woman than to feminise a man—and [testosterone] really acts very quickly,” she said.

And although a double mastectomy was “obviously irreversible,” Dr Cass said detransitioned women faced the “paradox” that “it is harder to pass as a woman if you’ve taken masculinising hormones at [age] 16.”²

“By 18, it’s harder to reverse that and pass as a woman again, than it is if you’ve had a mastectomy—you can do more about that cosmetically than you can about having a deep voice and facial hair.

“It is important to say that, however careful the assessment [before hormonal treatment], it’s really difficult to determine with any sense of certainty which young people will go on to have an enduring trans identity.”

Although gender clinics claim there is little treatment regret, the Cass report says: “The percentage of [young] people treated with hormones who subsequently detransition remains unknown due to the lack of long-term follow-up studies, although there is suggestion that numbers are increasing.”³

Given the risks and unknowns, the report urges “an extremely cautious clinical approach” to any cross-sex hormone provision at age 16, when this intervention becomes available under some treatment guidelines. In Australia, younger girls are put on testosterone, which is meant to be taken lifelong⁴.

Noting the lack of good evidence, the Cass report says: “No conclusions can be drawn about the effect [of cross-sex hormones] on gender dysphoria, body satisfaction, psychosocial health, cognitive development, or fertility. Uncertainty remains about the outcomes for height/growth, cardiometabolic and bone health.”

The recording of the July 2 Cass webinar, hosted by Australia’s National Association of Practising Psychiatrists (NAPP), is here. The NAPP advises a cautious approach to management of youth gender distress.

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Video: How Seattle Children’s Gender Clinic presents testosterone for girls

“High testosterone levels in trans males (females who identify as trans) lead to high haemoglobin and haematocrit levels (red blood cell counts). Having too many red blood cells is a risk factor for cardiovascular disease and death. We believe that the female reference range for haemoglobin and haematocrit must be used for trans males in order to help them to understand their true risks. Furthermore, because of these risks and also lack of maturity, adolescent females with gender incongruence should never be prescribed testosterone.”—US endocrinologist Dr Michael K Laidlaw and colleagues, media statement, 1 December 2021

“The safety of an unknown number of teenage girls given testosterone by Australian gender clinics is in question following an extraordinary UK court case involving a 15-year-old girl thought to be at risk of sudden death because of a ‘dangerously high’ dose of this cross-sex hormone drug. A comparable ‘loading’ dose of adult testosterone is suggested as a starting dose for female adolescents in the 2018 ‘Australian standards of care’ treatment guideline issued by the Royal Children’s Hospital Melbourne.”—GCN, news report, 22 May 2024

Saving future choice

At the Australian webinar, picking up a key theme of her report, Dr Cass stressed how important it was for transgender identifying youth—girls dominate the mostly teenage caseload of gender clinics—to keep their options open as long as possible during a period of development and change.

“There’s a lot you can do with social transition [short of hormonal and surgical interventions],” she said.

“The issue of irretrievably linking medicalisation to how you express your gender is part of the challenge.

“I was speaking to a gay friend who said, ‘We’re not hung up on this. We present however we want to present in a more masculine, androgynous or feminine way. And we feel that we have more flexibility than some of the binary trans community where there’s real pressure to conform to an idealised male or female appearance’.”

“‘I genuinely think testosterone prescribing [for menopause] is completely out of control in the UK,’ said Dr Paula Briggs, a consultant in sexual and reproductive health at Liverpool Women’s hospital and chair of the British Menopause Society. ‘People are being led to believe that they must have this. But we have no idea what long-term testosterone supplementation does to women.’ ... Briggs’ biggest concern is that women will accidentally end up with excessively high or ‘supra-physiological’ levels of testosterone in their bodies, because their hormone levels are not being closely monitored.”—The Guardian, news report, 5 July 2024

“The risks of ‘masculinising hormone therapy’ (testosterone prescribed to females for identity reasons), on the other hand, are presented only after a declaration that testosterone ‘can be safe and effective when delivered by a health care provider with expertise in transgender care’. The Mayo Clinic also suggests that, in order to ‘minimise risks, medical providers will monitor patients in an attempt to keep ‘hormone levels in the range that’s typical for cisgender men’—never mind that female bodies aren’t male bodies. Testosterone levels in adult females typically range from 15 to 70 nanograms per decilitre, while typical male levels range from 300 to 1,000 nanograms per decilitre. On what basis, exactly, does dosing a female patient with 20 times her body’s natural testosterone levels represent cautious risk management?”—Eliza Mondegreen, comment article, UnHerd, 9 July 2024

In the dark

In the Cass-commissioned systematic review of hormone treatment, the University of York researchers say: “There is a lack of high-quality research assessing the outcomes of [cross-sex] hormone interventions in adolescents with gender dysphoria/incongruence, and few studies that undertake long-term follow up.”

The researchers note earlier systematic reviews, including a 2018 Pediatrics paper by Australian authors who reported that evidence on the psychosocial and cognitive impact of hormonal treatment in dysphoric youth was “generally lacking.”

Although the authors include Dr Ken Pang—the head of research at the gender clinic of the Royal Children’s Hospital (RCH) Melbourne—and the study had funding from the hospital foundation, this pioneering review with its discouraging results has not been cited in the 2018 RCH treatment guidelines used across Australia and now badged as an updated Version 1.4, 2023.

Another presenter at the July 2 webinar, Melbourne psychiatrist Alison Clayton, challenged the claim that Australia’s gender clinics already operate in line with the recommendations of the Cass report.

For one thing, Dr Clayton said, England had confined puberty blockers to a possible future clinical trial approved by a human research ethics committee, whereas these same drugs are available as routine treatment in Australia’s children’s hospitals.

In March this year, England’s National Health Service (NHS) announced an end to routine use of puberty blockers.

“NHS England has carefully considered the evidence review conducted by [the UK National Institute for Health and Care Excellence] and has identified and reviewed any further published evidence available to date,” the March statement said.

“We have concluded that there is not enough evidence to support the safety or clinical effectiveness of PSH [puberty suppressing hormones] to make the treatment routinely available at this time.”

Dr Clayton, a researcher affiliated with the Society for Evidence-based Gender Medicine, said the Trans20 research project at RCH Melbourne’s gender clinic was not a clinical trial because the blockers and hormones were being given as part of routine treatment.

“The Trans20 study’s ethics approval was not for the ‘routine treatments’ but for audits of data collected as part of routine clinical care and for contacting patients once they left the [RCH gender] service to ask them to complete the questionnaires,” Dr Clayton told GCN.

She also noted that the Cass report did not stipulate a “gender-affirming” treatment approach, whereas the 2018 RCH Melbourne treatment guidelines used in Australia are based on this contentious model.

Blocking the future

In the Australian webinar, Dr Cass cited the story told her by one parent “whose birth-registered boy was still using ‘he/him’ pronouns, sometimes went to school in a dress, sometimes wore more male-typical clothing, but he was very relaxed, the school were relaxed—and that seemed to be a bit more protective [against medicalisation] as he was approaching puberty.”⁵

She said puberty blocker drugs had enjoyed so much media coverage that “young people see them as almost totemic for the intervention that’s going to help them feel better and get them on to a medical pathway.”

She cited a finding from the London-based Tavistock clinic that children whose “stealth” trans identity was not public “were in a state of huge anxiety about being outed—and that was really driving an urgency for puberty blockers.”

Dr Cass said the goal should be to encourage minors to “keep gender expression flexible during that [developmental] period, if that’s possible,” because medicalisation could foreclose future choices.

The Cass report says, “there is no evidence that puberty blockers buy time to think, and some concern that they may change the trajectory of psychosexual and gender identity development.”⁶

Multiple independent systematic reviews have found the evidence for hormone suppression in gender-distressed minors to be very weak and uncertain. The puberty blocker review undertaken for Dr Cass by the University of York points out that this sobering conclusion is consistent with previous reviews, including the 2018 Pediatrics paper with its link to the RCH Melbourne gender clinic.

“I can’t think of another area of paediatric care where we give young people a potentially irreversible treatment and have no idea what happens to them in adulthood.”—Dr Hilary Cass, interview, the British Medical Journal, 9 April 2024

What exactly are we doing?

In the Australian webinar, Dr Cass made the point that even if positive outcomes were reported by a child given puberty blockers, it was difficult to disentangle “the extent to which we are treating the distress of puberty per se [it being an inherently unsettling phase].”

“So, working out exactly what impact puberty blockers have is really difficult.”

She also noted that the introduction of hormone suppression as routine treatment for gender-distressed children, without a sound basis in evidence, was a departure from medical norms.

“What happened is that a completely novel use of puberty blockers crept into clinical practice without appropriate scrutiny,” Dr Cass said.

She said this went beyond more familiar off-label uses, such as where a medicine approved to treat a condition in adults was used in children with the same condition (but without clinical trials to show efficacy and safety in those young patients).⁷

The Cass report says that “the focus on the use of puberty blockers for managing gender-related distress has overshadowed the possibility that other evidence-based treatments may be more effective.”

“The intent of psychosocial intervention is not to change the person’s perception of who they are, but to work with them to explore their concerns and experiences and help alleviate their distress, regardless of whether or not the young person subsequently proceeds on a medical pathway.”

The Cass-commissioned systematic review of psychosocial interventions for gender distress—such as cognitive behavioural therapy and attachment-based family therapy—found it was not possible to be confident about their effects because the studies were of low quality.

The University of York review included a study in Pediatrics reporting benefits on measures of depression, anxiety and quality of life among RCH Melbourne patients who went through the gender clinic’s nurse triage system including psychosocial support. But this Australian study was rated as low quality by the Cass-commissioned review.

Dr Cass told the webinar audience that the lack of evidence shown by the York review was specific to the question whether or not psychosocial interventions improved gender dysphoria, “largely because people haven’t looked at it.”

Her report recommends research into this question, and says “we know that many psychological therapies have a good evidence base for the treatment in the general population of conditions that are common in this [gender clinic patient] group, such as depression and anxiety.”

During the webinar discussion, Dr Cass agreed that all evidence-based therapies such as those for mental health conditions, neurodiversity issues and eating disorders should be offered to gender-distressed minors, rather than leaving them unsupported on a gender clinic waiting list.

GCN does not dispute that gender-affirming clinicians believe their treatment approach benefits vulnerable youth. Comment from RCH Melbourne was requested.

1. Australian champions of the “gender-affirming” treatment model, and some Australian health ministers, have played down the local relevance of England’s Cass review by making vague reference to differences between the two health systems.

2. Vaginal atrophy is expected to begin 1-6 months after a female starts taking testosterone to masculinise her body, according to the Endocrine Society of Australia. The society’s fact sheet says: “Testosterone therapy used for gender transition may reduce fertility... Before starting testosterone therapy, your doctor will discuss with you the option to have eggs frozen... Testosterone is a teratogen, meaning it can cause harm to unborn babies… The long-term effects of testosterone used for gender transition are not fully understood. There may be an increase in risk of heart (cardiovascular) problems… There are potential implications for bone health, however research so far is reassuring. Testosterone therapy is associated with polycythaemia (increased haemoglobin in the blood)... Some trans men on testosterone therapy develop pelvic pain, which is currently not fully understood. The effects on the risk of breast, uterine and ovarian cancer [are] not fully understood.”

3. A detransitioner is someone who ceases medical interventions and re-embraces birth sex.

4. Australia is also radical in allowing minors to undergo trans surgery. There is no good public data on the extent of this practice, although there are reported cases of double mastectomies at age 15. During the webinar, Dr Cass said: “In the UK, there is no intent to allow surgeries before 18.”

5. The data suggests that the vast majority of children who take puberty blockers will go on to cross-sex hormones, with risks including infertility and sexual dysfunction.

6. The Cass report says: “Adolescence is a time of overall identity development, sexual development, sexual fluidity and experimentation. Blocking this experience [with hormone suppression drugs] means that young people have to understand their identity and sexuality based only on their discomfort about puberty and a sense of their gender identity developed at an early stage of the pubertal process. Therefore, there is no way of knowing whether the normal trajectory of the sexual and gender identity may be permanently altered.” Surveys of patients at the London-based Tavistock gender clinic showed a high level of same-sex attraction.

7. In her report, Dr Cass rejects the argument that trans puberty blockade can make use of the track record of safety for hormone suppression in children entering puberty very early, pointing out that these are two quite different interventions.