Major uncertainties remain about the impact of puberty blockers and gender affirming hormone therapy on children and young people with gender related distress (gender dysphoria), making it impossible to determine conclusively whether they help or harm.
This is the finding of a study — “Puberty blockers for youth experiencing gender dysphoria: A systematic review and meta-analysis” by Anna Miroshnychenko — that appeared in the Archives of Disease in Childhood.
The study’s findings are said to echo those of the Hilary Cass review of gender identity services in the NHS, published last April 2024. This concluded that the evidence for the use of puberty blockers and masculinizing and feminizing hormones for gender related distress — psychological distress caused by a mismatch between birth sex and gender identity — was wholly inadequate, precluding the ability to gauge their effectiveness or impact on mental and physical health.
With a view to strengthening the evidence base and informing clinical practice and policy, the researcher pooled the results of the available research on the use of puberty blockers and gender affirming hormone therapy (GAHT) in children and young people with gender related distress up to the age of 26.
Puberty blockers aim to delay or prevent the onset of puberty by blocking the hormones that cause the physical changes associated with male and female gender identity. Meanwhile, GAHT, consisting of masculinizing and feminizing hormones, aims to induce and maintain the desired sex characteristics: facial hair or breast enlargement, for example.
Previously published systematic reviews of the effects of puberty blockers and GAHT in those with gender related distress haven’t analyzed the pooled data from the included studies, a process which enhances the reliability and scientific rigor of the individual study results and helps to resolve conflicting findings.
In the first of these analyses, the researcher assessed and summarized the certainty of the evidence about the effects of puberty blockers in 10 relevant studies: three comparative observational, and seven before and after, studies. The comparative observational studies comparing puberty blockers with none provided very low certainty evidence on the outcomes of global function — general health, quality of life, and psychological wellbeing — and depression. Similarly, the before and after studies provided very low certainty evidence on the impact of puberty blockers on global function, depression, and bone mineral density.
After synthesizing the results, the researcher concluded that there was no conclusive evidence on which to base policy and practice. “There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing (gender dysphoria). Methodologically rigorous prospective studies are needed to elucidate the effects of this intervention.”
The second analysis aimed to clarify the psychological and physical impact of GAHT and included 24 relevant studies: nine comparative observational studies; 13 before and after studies; and two case series.
Both the comparative observational and before and after studies provided very low confirmatory evidence of any substantive change, with just one observational study indicating that GAHT might lower the risk of depression.
The case series provided very low certainty evidence on death by suicide and high to moderate certainty evidence for cardiovascular events.
There’s a dearth of high quality evidence on which to base policy and practice, said the researcher, who concluded: “There is considerable uncertainty about the effects of gender affirming hormone therapy (GAHT), and we cannot exclude the possibility of benefit or harm. Methodologically rigorous prospective studies are needed to produce higher certainty evidence.”
