"Our main goal is to establish the effects of hormone intervention on frontal and prefrontal cortex development," explains Christian Beckmann. "To achieve this, we will follow a specific cohort of individuals undergoing clinical care in the Radboudumc Centre of Expertise for Sex & Gender."
The study will track two groups of young people: 100 individuals who have received GnRH analogues, medications that temporarily suppress puberty, and 100 who have not, just before they begin receiving cross-sex hormones. Participants will undergo extensive cognitive and behavioural assessments, alongside neuroimaging scans, at baseline and at intervals of 12-18 months. This unique longitudinal approach will allow researchers to observe changes in brain development over time.
Addressing a critical debate
The study is relevant to current debates about the safety and effectiveness hormonal treatments for (young) people with gender dysphoria. "There is significant discussion about whether these treatments are truly safe and beneficial," says Hedi Claahsen. Questions remain about their long-term effects, especially on psychosexual development and cognitive functioning.
In the Netherlands, GnRH analogues are commonly used to delay puberty in adolescents until they are eligible for cross-sex hormone treatment at age 16. While this approach can help prevent the development of unwanted secondary sexual characteristics, open questions relate to broader effects. "We hope our research will provide answers regarding the neurological and psychological impact of this treatment," Claahsen adds.
Investigating long-term effects
The project will also revisit a previous study conducted between 2007 and 2014 in Amsterdam. "A second arm of our research involves following up with individuals who participated in that earlier study," Beckmann explains. "We will examine the long-term effects of hormone intervention by analysing their development over time. This work is being done in collaboration with Sarah Burke from the UMC Groningen.
The team also aims to explore the high prevalence of co-occuring conditions such as autism, and depression, among individuals seeking gender-affirming care. "We do not fully understand why these conditions co-occur at such high rates," says Claahsen. "By studying brain development in this population, we may be able to uncover important connections and improve future approaches to improve people’s well-being."
Unique opportunity for fundamental research
In addition to its clinical relevance, the study presents a rare opportunity for fundamental neuroscience research. "This period of adolescence is a time of major neural change, under the influence of sex hormones, but we cannot manipulate hormone levels for research purposes," says Guusje Collin. "However, because these interventions are already part of clinical care, we can study their effects in a naturalistic setting."
The findings could have far-reaching implications, not only for gender-affirming care but also for our broader understanding of how sex hormones influence brain development. "Ultimately, we hope our work will contribute to better-informed medical decisions and improved care for transgender youth," Beckmann concludes.