Transition from assigned sex at birth to individual gender identity in cases of differences of sex development
Makaleler > Tam Makale · 2025
Yazarlar: ARZU JALİLOVA, Samim ÖZEN, Deniz ÖZALP KIZILAY, BEGÜM YULUĞ TAŞ, Aslı ECE SOLMAZ, HANİFE GÜL BALKI, Ali TEKİN, Emrullah ARSLAN, Tahir ATİK, KÜBRA GÜRPINAR, Muhsin Özgür ÇOĞULU, Gökçen ÜNAL KOCABAŞ, Nazlı Burcu ÖZBARAN, HÜSEYİN ONAY, İbrahim ULMAN, Feriştah Ferda ÖZKINAY, Lütfiye Füsun SAYGILI, Ruhsar Damla GÖKŞEN, Şükran DARCAN
The Journal of Sexual Medicine, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2025, cilt 22, ss 2154-2156
Özet
Differences of sex development (DSD) refer to a spectrum of conditions where there is a discrepancy between an individual’s genetic, gonadal, and phenotypic sex. Although rare, these conditions can profoundly impact the quality of life and psychosocial well-being of affected individuals. One of the most significant challenges associated with DSD is the potential misalignment between the sex assigned at birth and the individual’s self-identified gender later in life.1,2 In clinical practice, sex assignment at birth is typically based on the appearance of external genitalia. However, in DSD cases, chromosomal, gonadal, or hormonal abnormalities can complicate this assignment, resulting in uncertainty regarding gender identity throughout childhood, adolescence, and adulthood.3 Gender identity is defined as an intrinsic sense of being male, female, or another gender, typically forming during early life stages. However, in individuals with DSD, gender identity may differ from assigned sex at birth and can evolve over time. This complexity poses significant psychosocial challenges for both individuals and their families. The present study aimed to investigate the trajectory of gender identity development in individuals with DSD, specifically focusing on the transition from assigned sex at birth to self-identified gender. We conducted a retrospective analysis of 154 patients diagnosed with DSD between 1983 and 2023 at a single center. The data collected included demographic characteristics, initial diagnosis, follow-up duration, clinical outcomes, and changes in gender identity over time. To maintain consistency and reduce heterogeneity, patients with Turner syndrome, Klinefelter syndrome, isolated micropenis, and isolated hypospadias were excluded from the study. The study protocol received approval from the Ege University Ethics Committee (Approval No. 24-7T/43). The mean age at initial presentation was 7.7 ± 6.4 years (range: 0-18), with a median of 6.5 years (IQR: 2.0-12.0). The mean follow-up duration was 13.4 ± 8.1 years, with a median of 13.4 years (IQR: 7.0-20.0). Among the study population, 63 patients (41%) had a 46,XX karyotype, 75 (48.7%) had a 46,XY karyotype, and 16 (10.3%) had sex chromosome abnormalities. Within the 46,XX group, congenital adrenal hyperplasia (CAH) was the most common diagnosis, observed in 44 patients (69.9%). Other diagnoses included Müllerian duct anomalies and gonadal dysgenesis. Notably, 6 patients with a 46,XX karyotype, all with a diagnosis of CAH, were raised as males, and 2 of them underwent a transition from male to female identity during follow-up. In the 46,XY group, the most prevalent diagnoses included testosterone biosynthesis disorders (41.3%), androgen insensitivity syndrome (22.7%), and gonadal dysgenesis (24%). Of the 46,XY individuals who were raised as females, 36 (49.3%) continued to identify as female, indicating consistency in gender identity within this subgroup, while 9.3% transitioned to a male identity later in life. In cases with sex chromosome abnormalities, 43.7% were assigned male at birth, with one transitioning to female during follow-up. In total, 92.9% of the study population maintained their assigned sex at birth, while 7.1% experienced a change in gender identity. Table S1 provides a detailed analysis of all cases, including specific diagnoses and gender identity outcomes. The complexity of gender identity development in DSD is influenced by genetic, hormonal, social, and environmental factors. Although sex assignment at birth is often based on genital appearance, there is growing recognition that genetic and hormonal influences may play a more critical role than previously assumed. For instance, individuals with CAH exposed to elevated androgens in utero generally continue to identify as female if raised accordingly, despite masculinized genitalia. However, delayed diagnosis or inadequate management may result in gender dysphoria and later transition. Our findings suggest that male sex assignment in individuals with 46,XX CAH may not always align with long-term gender identity, as several patients in our cohort who were initially raised as males later identified as female. This observation is consistent with previous reports indicating that individuals with 46,XX CAH more frequently maintain a female gender identity when raised as female, supporting recommendations for female sex assignment in such cases.1 In individuals with 46,XY DSD, the relationship between androgen action and gender identity is complex. While those with complete androgen insensitivity syndrome typically maintain a female identity, individuals with partial AIS or testosterone biosynthesis defects may shift toward a male identity during puberty. These variations highlight the need for individualized care and the avoidance of early irreversible interventions that may not align with the individual’s evolving gender identity. Among the 7 individuals in our cohort with androgen synthesis defects (including 5α-reductase or 17β-HSD-3 deficiency) assigned female at birth, most transitioned to a male identity during adolescence. This finding is consistent with the DSD-LIFE study, which reported diagnosis-dependent patterns of gender change, with more female-to-male transitions in androgen synthesis disorders and male-to-female transitions in CAH and sex chromosome anomalies.4 Determining the timing of surgical interventions remains a major challenge. Historically, early surgical correction was preferred to reduce stigma, but evidence indicates a risk of regret if gender identity later diverges from the assigned sex.3 Current guidelines therefore favor deferring irreversible procedures until the individual can participate in decision-making. Psychosocial support is another cornerstone of DSD care. Gender identity development requires a multidisciplinary approach involving endocrinologists, psychologists, geneticists, and social workers. Educating families about the potential for evolving gender identity can reduce confusion and anxiety. An important observation from our study is that most individuals maintained the sex assigned at birth, while a minority experienced transitions, emphasizing the unpredictability of gender identity outcomes. This finding aligns with previous studies indicating that genetic, hormonal, and psychosocial factors collectively shape gender identity development.1 Given the diversity of outcomes, healthcare providers must approach DSD management with flexibility and openness to the possibility of change over time. Our findings underscore the importance of considering long-term psychosocial outcomes when evaluating early sex assignment decisions in individuals with DSD. Avoiding premature decisions and involving individuals in their care is essential. Early comprehensive genetic and hormonal evaluations can guide management plans. In conclusion, our findings support the general consensus that the management of DSD should follow an individualized and multidisciplinary approach to optimize long-term outcomes. By focusing on patient-centered care and promoting informed decision-making, healthcare providers can better support individuals and families facing the challenges of DSD. Given the complexity of gender identity development, it is crucial to respect patient autonomy and facilitate informed choices. Continued research into the long-term outcomes of various management strategies will be vital in refining best practices and enhancing the quality of care for individuals with DSD. We would like to express our gratitude to all the participants and their families for their cooperation in this study. A.J.: Conceptualization-Lead, Project administration-Lead, Writing—original draft-Supporting, Writing—review & editing-Lead. S.O.: Data curation-Equal, Methodology-Equal, Resources-Equal, Writing—review & editing-Equal. D.K.Ö.: Resources-Equal, Software-Equal, Validation-Equal. B.Y.T.: Formal analysis-Equal, Funding acquisition-Equal. A.E.S.: Funding acquisition-Equal, Methodology-Equal, Supervision-Equal. H.G.B.: Resources-Equal, Software-Equal. A.T.: Validation-Equal, Visualization-Equal. E.A.: Formal analysis-Equal, Methodology-Equal, Software-Equal. T.A.: Resources-Equal, Supervision-Equal. K.G.: Formal analysis-Equal, Funding acquisition-Equal. O.C.: Formal analysis-Equal, Methodology-Equal. G.Ü.K.: Resources-Equal, Software-Equal. B.O.: Supervision-Equal, Writing—original draft-Equal. H.O.: Resources-Equal, Validation-Equal. I.U.: Conceptualization-Equal, Data curation-Equal. F.O.: Supervision-Equal, Validation-Equal. F.S.: Validation-Equal, Visualization-Equal. D.G.: Supervision-Equal, Writing—review & editing-Equal. Ş.D.: Methodology-Equal, Writing—review & editing-Equal. None declared. None declared. Ethical clearance was officially received from the Ege University Ethics Committee (Approval No. 24-7T/43). This study was conducted in accordance with the principles of the Declaration of Helsinki.