Gender dysphoria in congenital adrenal hyperplasia: A review of the cases described in the literature.

BACKGROUND

Gender dysphoria (GD) has been reported in individuals with classic congenital adrenal hyperplasia (CAH), but its frequency and predictors among 46, XX patients raised female remain poorly characterized. Understanding the influence of androgen exposure, timing of diagnosis, and treatment adherence is essential for sex assignment, surgical planning, and long-term follow-up in pediatric urology.

OBJECTIVE

To systematically review published cases of 46, XX CAH patients assigned female who developed GD or changed social gender, focusing on Prader stage, age at diagnosis, and treatment adherence.

METHODS

A systematic search of PubMed, Embase, and Cochrane Central was conducted through January 2025 using the terms ("Congenital adrenal hyperplasia" OR "CAH" OR "21-hydroxylase deficiency" OR "adrenogenital syndrome") AND ("gender identity" OR "gender dysphoria" OR "gender incongruence" OR "gender nonconformity"). Inclusion criteria were original articles reporting 46, XX CAH individuals raised as females who presented GD; studies on non-classic CAH, animals, individuals under 12 years, and review articles were excluded. Extracted data included age at diagnosis, Prader classification, CAH type, surgery, medication adherence, GD assessment method, social gender change, sexual orientation, and psychosocial variables.

RESULTS

Thirteen studies met the inclusion criteria, describing 19 cases of 46, XX CAH patients assigned female who developed GD and/or transitioned socially to male. Overall, 15/19 cases had at least one of: (a) marked virilization (Prader 4-5 or highly virilized), (b) late diagnosis, or (c) poor/irregular adherence to glucocorticoid therapy. Sexual orientation, when reported, was mainly female-directed, and eleven patients had socially transitioned to male at the time of report.

CONCLUSIONS

GD in 46, XX CAH patients raised female appears linked to higher cumulative androgen exposure, delayed diagnosis, and poor treatment adherence. Early diagnosis and consistent therapy may be protective.