Performance of mass spectrometry steroid profiling for diagnosis of polycystic ovary syndrome.

Study Question: How well does multi-analyte steroid mass spectrometry (MS) profiling classify women with and without polycystic ovary syndrome (PCOS)?
Summary Answer: Our liquid chromatography MS (LC-MS) steroid profiling only minimally improves discrimination of women with and without PCOS compared with a direct testosterone immunoassay (T_IA) and the free androgen index (FAI).
What Is Known Already: Blood testosterone measured by direct (non-extraction) immunoassay overlaps between women with and without PCOS. Multi-analyte MS provides greater specificity and accuracy for steroid measurement so might improve the classification.
Study Design, Size, Duration: An observational, cross-sectional study of women with PCOS (n = 152) defined by Rotterdam criteria and matched non-PCOS (n = 45) control women was conducted.
Participants/materials, Setting, Methods: Serum steroid profiles of testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), androstenedione (A ₄ ), estradiol (E ₂ ), estrone (E ₁ ), 17 hydroxy progesterone (17OHP ₄ ), progesterone (P ₄ ) and cortisol were measured by LC-MS; T_IA and sex hormone binding globulin were measured by immunoassay; and FAI, calculated free testosterone (cFT) and total androgen index (TAI) were calculated. Classification was based on logistic regression with corresponding univariate and multivariate C-statistics.
Main Results and the Role of Chance: Serum testosterone by immunoassay demonstrated levels more than 100% higher than that measured by LC-MS. Compared with the controls, women with PCOS had higher serum T, DHEA, A ₄ , TAI, T_IA, cFT, FAI and E ₂ but not serum DHT, E ₁ , P ₄ , 17OHP ₄ or cortisol. Univariate C-statistics were highest for FAI (0.89) and T_IA (0.82) compared with other androgens (T [0.72], DHT [0.40]), pro-androgens (A ₄ [0.74], DHEA[0.71]) or derivatives (cFT [0.75], TAI [0.60]). For all multivariate models, the overall correct predictions (81-86%) featured high sensitivity (92-96%) but low specificity (28-43%). and substituting LC-MS steroid measurements for T_IA and FAI produced only minimal improvements in classification.
Limitations Reasons for Caution: The study cohort is limited in size and only unconjugated steroids were measured.
Wider Implications of the Findings: Multi-analyte steroid profiling of unconjugated circulating steroids provides only limited improvement on direct T_IA in classifying women with and without PCOS.
Study Funding/competing Interests: None.
Trial Registration Number: N/A.
(© Crown copyright 2016.)