TOPLINE

Combined oral contraceptives containing ethinyloestradiol and levonorgestrel markedly reduced plasma and urinary androgen levels and their metabolites in adolescent and young females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), while simultaneously increasing total cortisol levels.

METHODOLOGY

• Researchers conducted a multicentre observational study to evaluate the effects of combined oral contraceptives on plasma and urinary steroid profiles in adolescent and young females with CAH due to 21OHD.
• Of 20 adolescent and young females enrolled, 17 (median age, 16.8 years) completed the study after initiating a combined oral contraceptive containing ethinyloestradiol 0.03 mg and levonorgestrel 0.15 mg; eligible participants had a genetically confirmed diagnosis, had achieved Tanner stage B4 or higher and a bone age of at least 14 years, and were on no long-term medication other than hydrocortisone and fludrocortisone as needed.
• Blood and urine samples were collected across three visits: prior to the initiation of oral contraceptives, during the third oral contraceptive cycle, and during the sixth oral contraceptive cycle.
• Plasma steroid profiles were quantified using liquid chromatography-mass spectrometry and urinary steroid metabolites were quantified using gas chromatography-mass spectrometry in 16 participants with complete urine data.

TAKEAWAY

• Following oral contraceptive treatment, plasma levels of 17-alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, and testosterone decreased markedly from baseline, whereas cortisol levels increased.
• Urinary androgen metabolites — including androsterone (P < .001), etiocholanolone (P = .002), dihydroandrosterone (P = .008), 11-oxo-etiocholanolone (P = .002), 11-beta-hydroxyandrosterone (P < .001), dehydroepiandrosterone (P = .002), androstenetriol (P = .002), testosterone (P < .001), and dihydrotestosterone (P < .001) — decreased markedly; the sum of urinary androgen metabolites fell from a median of 2569.2 to 726.6 nmol/24 h (P < .001).
• The urinary CAH marker 11-oxo-pregnanetriol declined significantly (P < .001). Although urinary cortisol rose (P = .002), the overall sum of urinary cortisol metabolites decreased (P < .001), pointing to altered cortisol metabolism and clearance; mineralocorticoid metabolites also declined (P < .001).
• Treating physicians reduced hydrocortisone doses in 47% of participants based on biochemical changes.

IN PRACTICE

"[The study] findings deepen our understanding of the biochemical effects of OCs [oral contraceptives] in CAH and highlight their potential value as an adjunctive therapy for patients who are not seeking pregnancy and continue to exhibit persistent androgen excess despite standard glucocorticoid treatment," the authors wrote.

SOURCE

The study was led by Chrysanthi Kouri, Paediatric Endocrinology, Diabetology and Metabolism, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. It was published online on August 21, 2026, in the European Journal of Endocrinology.

LIMITATIONS

The relatively small sample size may have prevented the detection of meaningful changes or trends in data. The observational design restricted the causal association between oral contraceptive use and biochemical changes.

DISCLOSURES

This study was supported by Stiftung Batzebär and the International Fund raising for research on CAH. One author declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.