A new systematic review has cast doubt on the certainty of evidence surrounding the effects of puberty blockers, calling for more rigorous studies to better understand their impact. The review, which analysed existing research on the use of these medications in individuals with gender dysphoria, found that the current body of evidence is of very low certainty, making it difficult to draw firm conclusions about their benefits or potential risks. The findings were published in the journal Archives of Disease in Childhood.
Puberty blockers, also known as gonadotropin-releasing hormone analogues, are used to delay the development of secondary sexual characteristics. Originally developed to treat conditions such as precocious puberty, they have become a widely discussed option for young people experiencing gender dysphoria. The rationale behind their use is to provide individuals with more time to explore their gender identity before making further decisions regarding medical transition. But concerns have been raised about the long-term effects of these medications, particularly in relation to bone development and mental health outcomes.
The systematic review assessed the available studies using the highest methodological standards. Despite these efforts, researchers found that much of the data on puberty blockers comes from case series and before-and-after studies, which lack the comparative rigour of randomised controlled trials. This limitation, coupled with small sample sizes and issues of bias, resulted in the certainty of evidence being rated as very low across most outcomes examined. Professor Gordon Guyatt of McMaster University acknowledged these limitations but cautioned against misinterpreting the findings. “I am concerned that the valid conclusions of our work – that only low certainty evidence exists regarding the benefits of the gender-affirming care interventions addressed in our review – will be misused. Specifically, I am concerned our findings will be used to justify denying these interventions to individuals seeking them.”
Among the outcomes evaluated were global function, depression, gender dysphoria, bone mineral density, and the likelihood of progressing to gender-affirming hormone therapy. The findings indicated that while some studies reported improvements in psychological well-being, others showed little to no effect. Data on the impact of puberty blockers on bone health was inconclusive, with some evidence suggesting a reduction in bone mineral density during treatment. The review also highlighted that the majority of individuals who begin puberty blockers go on to receive gender-affirming hormones, although the reasons behind this pattern remain unclear. Professor Guyatt stressed that these findings should be used to guide informed decision-making rather than to prohibit access. “Forbidding management options on the basis of low certainty evidence is a clear violation of the principles of evidence-based shared decision-making and is unconscionable.”
One of the key issues identified in the review was the lack of studies using control groups. Without comparisons to individuals who did not receive puberty blockers, it is difficult to determine whether observed changes are due to the medication itself or other factors. Additionally, some important outcomes, such as regret and long-term sexual function, were not assessed due to insufficient data. Guyatt underscored the ethical obligation to respect patient autonomy in light of these uncertainties. “Following the principles of evidence-based decision-making, clinicians should always have a high respect for the autonomy of patients and their advocates – in the case of adolescents, their parental advocates. The high respect for autonomy becomes particularly important when the certainty of the evidence is low or very low.”
Given these limitations, the researchers have called for more robust studies, including prospective cohort studies and, where ethical, randomised controlled trials. They emphasised the importance of ensuring that individuals, families, and clinicians are provided with clear information about the current level of uncertainty in the evidence base. As Guyatt pointed out: “The appropriate use of our work is in helping with informed decision-making for individuals experiencing gender dysphoria in arriving at decisions regarding their medical management.”
