'Considerable uncertainty' remains about gender treatments for kids, Canadian researchers warn

Two new major reviews by Canadian researchers echo findings of U.K. review that led to ban on puberty blockers for trans-identifying youth

By Sharon Kirkey
Published Jan 24, 2025
Last updated Jan 27, 2025
5 minute read
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A doctor and young patient.
"Since the current best evidence, including our systematic review and meta-analysis, is predominantly very low quality, clinicians must clearly communicate this evidence to patients and caregivers," researchers wrote. Photo by Getty Images

The evidence surrounding the use of puberty blockers and cross sex hormones in children and teens identifying as transgender is of such low certainty it’s impossible to conclude whether the drugs help or harm, Canadian researchers are reporting.

Doctors should “clearly communicate” the major uncertainties that remain with children and parents and check “whose values they are prioritizing” when prescribing puberty blockers and masculinizing or feminizing hormones to youth, they write.

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Their findings echo those of a major British review, commissioned by the National Health Services of England, that found evidence for the safety and efficacy of puberty blockers for children with gender dysphoria is remarkably weak and “built on shaky foundations.”

Following the Cass Review’s release last March, doctors in the U.K. were told to temporarily stop routinely prescribing puberty blockers to under-18s.

In December, the ban was made indefinite after independent expert advice concluded the drugs pose an “unacceptable safety risk” to children.

The Cass Review hasn’t altered the gender-affirming approach to care in Canada. The Canadian Paediatric Society has criticized what it has called “significant limitations, biases and inaccuracies” within the review, which capped off a four-year inquiry. In a letter published in its flagship journal, the society said that “the model of gender-affirming care in Canada differs in many ways from the approach that had been in place in the U.K.”

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However, one federally funded study that followed 174 children who were under 16 when they were referred to one of 10 gender identity clinics in Canada found 74 per cent were put on puberty blockers. Nearly two-thirds went on to masculinizing or feminizing hormones.

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Hours after being sworn in as U.S. president this week, and to the alarm of LGBTQ and human rights groups, Donald Trump signed an executive order declaring the U.S. will only recognize two sexes, male and female, and that a person’s sex is unchangeable.

The use of medical interventions in children identifying as transgender or non-binary remains controversial. “There’s not enough reliable information,” said Chan Kulatunga-Moruzi, one of the authors of the two new reviews.

“We really don’t have enough evidence to say that these procedures are beneficial. Few studies have looked at physical harm, so we have really no evidence of harm as well. There’s not a lot that we can say with certainty, based on the evidence.”

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Puberty blockers delay or prevent the onset of puberty by blocking the release of hormones that cause puberty’s physical changes, which normally begin between the ages of eight and 13 for females, and nine and 14 for males.

The drugs are said to give children identifying as transgender more time to decide if they want to transition while easing the distress of feeling as if their bodies are changing in unwanted ways.

Most youth who start puberty blockers progress to gender-affirming hormones, drugs that aim to induce desired sex characteristics like facial hair, or breast enlargement. Concerns have been raised that the drugs are “locking in” a gender identity, making their transition a foregone conclusion.

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Doctors who treat gender dysphoric children argue that puberty suppression doesn’t impede the usual process of sexual orientation or gender identity development.

Originally considered fully reversible, concerns are emerging about potential long-term or irreversible effects, the Canadian team wrote this week in the journal, Archives of Disease in Childhood. Questions have been raised about the effects on fertility or what impact, if any, they might have on brain development.

The Canadian team combed the available evidence, pooling the results of research on puberty blockers and gender affirming hormones for children and youth up to age 26. They graded the evidence using a scoring system co-developed by Dr. Gordon Guyatt, a celebrated McMaster University scientist who coined the phrase evidence-based medicine.

After screening 6,736 titles and abstracts involving puberty blockers, only 10 studies were included in their review. While children who received puberty blockers compared to those who don’t score higher on “global function” — quality of life, and general physical and psychological wellbeing — the evidence was of “very low certainty.” Very low, meaning researchers have “very little confidence in the effect estimate” and that the true effect “is likely to be substantially different from the estimate of effect.”

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We really don't have enough evidence to say that these procedures are beneficial

The studies also provided low certainty of evidence on the impact of puberty blockers on depression. While they may decrease depression in “male-to-female participants,” they didn’t decrease depression scores in the female-to-male group. “We are very uncertain about the causal effect of the (drugs) on depression,” the researchers wrote.

“Most studies provided very low certainty of evidence about the outcomes of interest thus, we cannot exclude the possibility of benefit or harm,” they said.

The second review to assess the impact of hormone therapy (testosterone for females, estrogen for males) included 24 studies. That review also provided “very low confirmatory evidence of any substantive change” in gender dysphoria, depression or overall health, according to a release from the publishing group, BMJ Group.

Many studies suffered from missing data, small sample sizes or lacked a comparison group. The researchers said they didn’t find data for outcomes of death by suicide.

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“Since the current best evidence, including our systematic review and meta-analysis, is predominantly very low quality, clinicians must clearly communicate this evidence to patients and caregivers,” they wrote.

“Treatment decisions should consider the lack of moderate- and high-quality evidence, uncertainty about the effects of puberty blockers and patient’s values and preferences,” they added.

Guideline developers and policy makers should be transparent “about which and whose values they are prioritizing when making recommendations and policy decisions,” they said.

The research was funded by the Society for Evidence-based Gender Medicine, or SEGM, and McMaster University. SEGM has been accused of being an “anti-trans psychological and sociological think tank” by transgender rights groups. Despite the sharp push back, SEGM “has inarguably brought together clinicians and researchers who believe that the United States is becoming an outlier in its approach to pediatric gender medicine,” Undark’s Frieda Klotz wrote in a profile last year of SEGM co-founder, endocrinologist Dr. William Malone.

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