Androgen profiling in adolescent girls with polycystic ovary syndrome

To characterize global steroid hormone dysregulation and the androgen profile in adolescent girls with polycystic ovary syndrome (PCOS), and to explore adrenal versus ovarian androgen origins using a dexamethasone suppression test combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS).

We consecutively enrolled 37 adolescent PCOS patients and 22 age-matched healthy controls. PCOS diagnosis followed the 2023 international evidence-based recommendations. All participants underwent clinical evaluation and LC-MS/MS steroid profiling; 24 PCOS patients also received a dexamethasone suppression test.

Compared with healthy controls, the PCOS group had elevated levels of multiple androgens, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (AD), total testosterone (TT), androsterone (ADT), dihydrotestosterone (DHT), 11β-hydroxyandrostenedione (11-OHAD), 11β-hydroxytestosterone (11-OHT), and epitestosterone (EpiT), as well as estrone, pregnenolone, and 17-hydroxyprogesterone, along with decreased sex hormone-binding globulin (SHBG). Spearman correlation showed that DHEA-S explained only limited variation in 11-OHAD (r_s = 0.629, P < 0.001). ROC analysis identified the free androgen index (FAI) as the best diagnostic marker (AUC = 0.976, sensitivity 91.7%, specificity 87.0% at cutoff 4.27). FAI alone was elevated in 86.5% of PCOS patients; adding total testosterone and androstenedione increased detection to 97.3%. In the dexamethasone suppression test, DHEA, DHEA-S, and 11-oxygenated androgens were markedly suppressed (median inhibition 81.9%-92.2%), whereas testosterone suppression was minimal (14.0%, P = 0.522). Notably, baseline DHEA-S was not elevated in most patients with significant androgen suppression, indicating discordance between suppression-test-defined adrenal dominance and traditional DHEA-S criteria.

Adolescent girls with PCOS exhibit widespread androgen abnormalities. FAI demonstrates the highest diagnostic value, and the addition of total testosterone and androstenedione modestly improves detection. The dexamethasone suppression test suggests that most 11-oxygenated androgens are of adrenal origin, whereas testosterone suppression is minimal. Elevated DHEA-S levels are not consistently aligned with adrenal-origin androgen dominance defined by the suppression test. These findings warrant further validation in larger populations.