Total Testosterone Measured by Liquid Chromatograph-Tandem Mass Spectrometry Refines Diagnosis of Biochemical Hyperandrogenism and Better Identifies Subgroup at Genuine Risk of Adverse Fertility Outcomes in Women With Polycystic Ovary Syndrome

Abstract

Purpose: To compare total testosterone (TT) measured by liquid chromatograph-tandem mass spectrometry (LC-MS/MS) with electro-chemiluminescent immunoassay (ECLIA) in the diagnosis and management of infertile women with polycystic ovary syndrome (PCOS).

Methods: Baseline TT was measured by LC-MS/MS and ECLIA in 906 infertile women with PCOS. The associations of TT from both methods with clinical phenotypes and fertility outcomes were estimated; relative risk (RR) and 95% confidence intervals (CIs) were computed. Subgroup analysis was conducted according to the TT levels.

Results: The average TT levels measured by ECLIA were higher than those measured by LC-MS/MS (mean percentage difference 23.8%, 95% limits of agreement -44.2% to 91.9%). When biochemical hyperandrogenism (HA) defined as TT ≥ 1.7 nmol/L by LC-MS/MS method, a higher proportion of patients were identified having biochemical HA using ECLIA (44.0% vs. 24.0%, p < 0.001) than LC-MS/MS. Only those with TT levels ≥ 1.7 nmol/L measured by LC-MS/MS had an increased risk of adverse fertility outcomes compared to patients with normal TT levels, including ovulation, preterm labor, and neonatal intensive care unit.

Conclusion: Our findings indicated that LC-MS/MS refined the diagnosis of biochemical hyperandrogenism and better identified the subgroup at genuine risk of adverse fertility outcomes in infertile women with PCOS.

Trial registration: The NIH Clinical Trial Registry number: NCT01573858 and Chinese Clinical Trial. Registry number: ChiCTR-TRC-12002081.

Keywords: biochemical hyperandrogenism; liquid chromatograph‐tandem mass spectrometry; polycystic ovary syndrome; total testosterone.