Biochemical control in young women with congenital adrenal hyperplasia taking oral contraceptives: a prospective observational study.

OBJECTIVE: Androgen excess in 21-hydroxylase deficiency (21OHD) remains difficult to manage in adolescent females. Combined oral contraceptive(s) (OC) containing ethinylestradiol and progestin modulate ovarian and adrenal steroidogenesis, but their specific impact on 21OHD has not been systematically evaluated. We therefore examined how combined OCs influence the steroid metabolome in young women with classic 21OHD. DESIGN: Prospective observational study. METHODS: Young women aged 11-24 years with classic 21OHD who planned to initiate combined OC were enrolled. The study comprised three visits and included blood sampling and 24-h urine collection: Visit 1 before OC initiation, Visit 2 during the 3rd OC cycle, and Visit 3 during the 6th OC cycle. Plasma steroids were quantified by liquid chromatography-mass spectrometry and urinary metabolites by gas chromatography-mass spectrometry. Differences in steroid and metabolite levels across visits were assessed using the Friedman test. RESULTS: Of the 20 participants recruited, 17 (median age 16.8 years, range 11-24) completed the study. Compared with baseline, plasma concentrations of 17α-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, and testosterone decreased significantly (all p < 0.005), while cortisol increased (p < 0.001). Urinary 24-h excretion of androgen metabolites, including 11-oxo-etiocholanolone, declined. Between visits 1 and 3, eight participants (47%) reduced their hydrocortisone dose in response to biochemical changes. CONCLUSIONS: Combined OCs were observed to modify steroid metabolism and lower androgen levels in women with classic 21OHD. OC therapy may serve as a useful adjunct in the management of androgen excess in this population, particularly when conventional glucocorticoid therapy alone does not achieve satisfactory biochemical control.