Reply: Mastectomy for Individuals with Gender Dysphoria Younger Than 26 Years: A Systematic Review and Meta-Analysis

We thank Lane et al. for their interest in our work, “Mastectomy for Individuals with Gender Dysphoria Younger Than 26 Years: A Systematic Review and Meta-Analysis.”1 Their primary concerns regard the age criteria chosen and the sponsor of the research, the Society for Evidence-based Gender Medicine (SEGM). We address each of these concerns. The rationale for the age cut-off is clearly explained in Table 1, Eligibility Criteria: “We selected this age threshold because … youth is commonly thought to extend to the midtwenties. For instance, the Centers for Disease Control and Prevention[2] and the United Nations[3] regard youth as age 14 to 24 yr; to be inclusive of individuals who are slightly older ... we decided to include all individuals younger than 26 yr.” Other organizations that define youth to be inclusive of those in their midtwenties include UNICEF,4 the National Institutes of Health,5 and the U.S. Department of Health and Human Services.6 Major psychiatric and mental health organizations (eg, American Psychological Association, American Academy of Child and Adolescent Psychology) frequently include “young adults” or “youth” (18 to 25 years old) alongside adolescents, justified by ongoing brain development and transition periods from pediatric to adult care. The Adolescent Brain Cognitive Development Study,7 a joint endeavor of the National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, and National Institute of Mental Health, includes youth into their midtwenties. Notably, some LGBT organizations, such as The Trevor Project, consider youth to be 13 to 24 years of age8; a recent systematic review of interventions to reduce suicide risk in transgender and gender diverse youth9 used the age cut off of 24; and a study of thrombosis risk in transgender youth receiving gender-affirming hormone therapy5 used an age cut off of 22. While we respect the right of Lane et al. to question this cut-off, we disagree that it is disputed that the brain continues to develop into the midtwenties, although we acknowledge individual differences. With regard to the down-rating of evidence, as explained in our article, we downgraded the studies for indirectness if they did not include more than 60% of the cohort under age 26. This is because our population of interest is youth, and findings from studies in which the sample is largely older cannot be confidently used to generalize to younger populations. We were not expecting to find studies in which the age cut-off is 26; we simply used the existing literature in a reasonable manner to address our research question. With respect to the response rate, reviewers often treat response rates below 70% as a potential source of bias, especially in survey-based surgical studies. While some may interpret this as being conservative, a 30% nonresponse bias can significantly skew the findings. Lane et al., citing the Southern Poverty Law Center,10 maintain that SEGM is “recognized as part of an anti-LGBTQ+ pseudoscience network and hate group.” To our knowledge, SEGM has not called for any bans on pediatric gender-affirming care, but it has advocated for an evidence-based approach. In fact, in United States v Skrmetti, of the 54 amicus briefs filed, SEGM was 1 of the 4 organizations to file a neutral amicus brief.11 We fail to understand how calling for scientific evidence to guide treatment is pseudoscience, anti-LGBTQ+, or hateful. Further, the Southern Poverty Law Center has admitted that its definition of hate is contested, and rightly so, because it has admitted that their designation of hate has no strict defining criteria, is subjective, and is their opinion.12 We are sympathetic to the concerns of Lane et al. regarding misuse of research. All research, including ours, has the potential to be misused. Given the disclosures from Boe v Marshall regarding the interference from the World Professional Association for Transgender Health in the commissioned systematic reviews from The Johns Hopkins University, as well as how the minimum age requirements for various treatments came to be removed in World Professional Association for Transgender Health Standard of Care Version 8,13,14 it is understandable that there are reservations. However, 1 of the 2 citations of this research in the Department of Health and Human Services report on gender dysphoria, the umbrella review,15 found our systematic review to be at low risk of bias. As outlined in our article, although the SEGM commissioned the research, they were only involved in the development of the research question and had no access to the work in progress or the final article. Since the methodologists on the team do not have anything to gain by publishing this work, do not work with this population, and do not have intellectual or financial conflicts of interest, we maintain that there is less opportunity for bias. The content area experts who supported the work remained entirely open to study findings throughout the process. DISCLOSURE The authors have no conflicts of interest to disclose. There was no funding support for this communication. The authors received a travel stipend for their presentation at a conference organized by the Society of Evidence-based Gender Medicine in September of 2025, after their involvement with the systematic reviews and after submission of this Reply. Dr. Kulatunga-Moruzi presented the findings of the systematic review. Dr. Montante presented on his experience with gender-affirming mastectomy.