Gender Role Behavior, Sexuality, and Psychosocial Adaptation in Women with Congenital Adrenal Hyperplasia due to<i>CYP21A2</i>Deficiency

TLDR

Gender‑atypical behavior has been reported in girls and women with congenital adrenal hyperplasia caused by CYP21A2 deficiency. The study aimed to evaluate psychosexual and psychosocial outcomes in women with CAH and relate them to CYP21A2 genotype. Sixty‑two Swedish women with CAH and matched controls completed a 120‑item questionnaire and the PGWB instrument, and participants were stratified into four CYP21A2 genotype groups. Women with CAH exhibited higher gender‑atypical behaviors—such as male‑dominant occupations, rough sports, interest in motor vehicles, and non‑heterosexual orientation—correlated with CYP21A2 genotype severity, while overall quality of life was unchanged, indicating a dose‑dependent effect of prenatal androgens and a need for psychological support.

Abstract

Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency.The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype.Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups.The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls.We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.