11-oxygenated androgens and their relation to hypothalamus-pituitary-gonadal-axis disturbances in adults with congenital adrenal hyperplasia

Context: Hypothalamus-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. Design: Cross-sectional single center study including 89 patients (N = 42 men, N = 55 women) with classic CAH. Main Outcome Measures: Differences in steroid markers in men with hypogonadism and women with secondary amenorrhea with a special focus on 11-ketotestosterone (11KT) and 11 beta-hydroxyandrostenedione (11OHA4). Results: Hypogonadotropic 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. 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism and in women with amenorrhea in comparison to those with a regular cycle (11KT: 5.2x; 11OHA4: 3.7x). 11-oxygenated androgens were not higher in men with TART than in those without. There was a negative association of 11KT and 11OHA4 with FSH but not with LH in men. As expected, all steroids were strongly correlated with each other and cases of disproportionally elevated 11-oxygenated an -drogens that could explain for HPG-disturbances or TART in otherwise controlled patients were rare and also found in eugonadal individuals. Conclusions: In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control.

Automated summary

In patients with classic CAH, disturbances in the hypothalamus-pituitary-gonadal (HPG)-axis are common, with elevated 11-oxygenated androgens identified in women with menstrual disturbances and men with hypogonadotropic hypogonadism. However, it remains unclear if measuring 11-oxygenated androgens is more effective than conventional markers in assessing androgen control in these patients.