Statement in Support of Excluding Turner Syndrome and Klinefelter Syndrome from Variations of Sex Development and Gender Dysphoria for the Purpose of Government Policy Decision-Making: A Position Statement

Government policymakers in many countries have recently moved toward a more restrictive approach to medical intervention for young individuals presenting with either variations of sex development or gender dysphoria. This may include passing legislation to prohibit treatment for pubertal induction until that individual becomes “sufficiently mature” to give consent, which would delay essential treatment for a non-specified period of time. The legislation particularly concerns treatment with puberty blockers and sex hormones in minors. We submit that individuals with Turner syndrome and Klinefelter syndrome, with confirmed female and male gender identity, respectively, should never be grouped together with variations of sex development or gender dysphoria for any policy that proposes restricting or delaying any such treatment.Turner syndrome, a condition only affecting females, is due to complete or partial absence of one of the X chromosomes. Klinefelter syndrome, a condition only affecting males, is due to the presence of an extra X chromosome. The overwhelming majority of Turner syndrome and Klinefelter syndrome individuals are, respectively, phenotypically identified and raised solely as girls or boys, without any ambiguity regarding sex assignment. Turner syndrome and Klinefelter syndrome are therefore not conditions of indeterminate sex or gender assignment. The vast majority of Turner syndrome girls have or will develop primary ovarian failure, which will lead to absence of development of the secondary sexual characteristics (i.e., lack of or incomplete puberty) and infertility. Likewise, the vast majority of Klinefelter syndrome males have or will develop testicular failure and infertility. For the Turner syndrome and Klinefelter syndrome patients, there exist well-established evidence-based standard of care [1‒3] medical interventions that consist of hormonally replacing their sex steroid insufficiencies to allow normal start and progress with puberty. Such restorative treatments further promote normal bone mineral development, prevent early-onset osteoporosis, and, in addition, support cardiovascular health, cognitive function, and wellbeing throughout life.The introduction of policies designed to delay these interventions should not be applied to the conditions of Turner syndrome or Klinefelter syndrome. Even in affected individuals who may have limited decision-making capacity, deprivation or delayed initiation of essential hormone replacement therapy would be considered unethical given the adverse effect on their health outcomes. The result would be inappropriately delayed induction of puberty, impaired physical development, significant psychosocial and emotional distress, lack of normal bone mineralization, as well as compromising overall health and the prevention of several other complications. For these reasons, we urge policymakers to explicitly exclude Turner syndrome and Klinefelter syndrome from any legislative or regulatory framework aimed at delaying the standard of care interventions or from increasing scrutiny of hormonal replacement therapy otherwise developed for very different situations such as for variations in sex characteristics or gender-affirming care. Respectfully submitted by the chairs of the International Consensus Guidelines for the Care of Girls and Women with Turner Syndrome [1], and the joint chair of DSD group (main thematic group 7) - ENDO-ERN (CH Gravholt).This statement has been endorsed by Professor Dr Aneta Gawlik-Starzyk, Chair of the Turner Syndrome Working Group for the European Society of Pediatric Endocrinology, hereby providing ongoing support to continue to follow internationally and interdisciplinary developed evidence-based recommendations for patient care.We would like to thank Prof Dr Aneta Gawlik-Starzyk and Prof Dr Mehul Dattani for their careful review of the draft.The authors declare no competing interests.This study was not supported by any sponsor or funder.P.F.B.: conceptualization, writing of the original draft, and editing and review of final submission; C.H.G.: writing, review, and editing of the draft.