Elevated 11-oxygenated androgens are not a major contributor to HPG-axis disturbances in adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Abstract

ContextHypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context.DesignCross-sectional single center study including 89 patients (N=42 men, N=55 women) with classic CAH.Main Outcome MeasuresIndependent predictors for hypogonadism in men and secondary amenorrhea in women with CAH with a special focus on 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4).ResultsHypogonadotropic hypogonadism was present in 23% of men and 61% of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28% of men. While 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism, in stepwise logistic regression, the only significant independent predictor for hypogonadism were elevated 17-OHP levels (B = 0.006; p = 0.039). Although 11KT (5.2x) and 11OHA4 (3.7x) levels were also significantly higher in women with amenorrhea in comparison to those with a regular cycle, the only significant predictor for amenorrhea were elevated total testosterone levels (B = 1.806; p = 0.040). 11-oxygenated androgens were not different in those with TART and those without. Of note, there were no significant differences in 11OHA4 or 11KT between those with a regular cycle and those currently on hormonal contraceptives.Conclusions11-oxygenated androgens do not seem to add additional information for explaining menstrual disturbances and hypogonadism in patients with CAH in comparison to established marker of disease control.HighlightsThe 11-oxygenated androgens 11-ketotestosterone and 11β-hydroxyandrostenedione are significantly elevated in men with CAH with hypogonadotropic hypogonadism and women with amenorrhea.Elevated 17-OHP levels in male patients and elevated testosterone levels in female patients are however the dominant predictor of HPG-axis disturbances.11-oxygenated androgens are not predictive for testicular adrenal rest tumors in men with CAH11-ketotestosterone and 11β-hydroxyandrostenedione levels do not seem to be influenced by intake of oral contraceptives.