BACKGROUND Biochemical hyperandrogenism is a hallmark and diagnostic feature of polycystic ovary syndrome (PCOS). However, the most accurate androgen measurement for assessing biochemical hyperandrogenism in PCOS diagnosis remains uncertain. OBJECTIVE AND RATIONALE This systematic review aimed to assess different androgen measures [including total testosterone (TT), calculated free testosterone (cFT), free androgen index (FAI), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), and dihydrotestosterone (DHT)] for accuracy in diagnosing biochemical hyperandrogenism in women with PCOS, to inform the 2023 International PCOS Evidence-based Guidelines. SEARCH METHODS To update evidence from the 2018 International PCOS Guidelines, a systematic search from 3 July 2017 to 23 June 2023 was conducted across Medline (Ovid), CINAHL, all EBM, EMBASE, and PsycInfo for articles evaluating androgens in the diagnosis of biochemical hyperandrogenism. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias and applicability. A diagnostic test accuracy meta-analysis was performed using STATA 18 software. Summary sensitivity and specificity were calculated with 95% CIs using the bivariate model, while the hierarchical summary receiver operating characteristics (ROC) model was used to produce a summary ROC curve. OUTCOMES Of 23 studies reviewed, 18 were included in the meta-analysis, with data from 2857 participants (1650 with PCOS and 1207 controls). For diagnosing biochemical hyperandrogenism in PCOS, the pooled sensitivity, specificity, and AUC with 95% CI were for TT: 0.74 (0.63–0.82), 0.86 (0.77–0.91), and 0.87 (0.84–0.90); cFT: 0.89 (0.69–0.96), 0.83 (0.79–0.86), and 0.85 (0.81–0.88); FAI: 0.78 (0.70–0.83), 0.85 (0.76–0.90), and 0.87 (0.84–0.90); A4: 0.75 (0.60–0.86), 0.71 (0.51–0.85), and 0.80 (0.76–0.83); and DHEAS: 0.75 (0.61–0.85), 0.67 (0.48–0.81), and 0.77 (0.73–0.81), respectively. In subgroup analyses, liquid chromatography with tandem mass spectrometry (LC-MS/MS) had superior sensitivity for measuring cFT, FAI, A4, and DHEAS, and superior specificity for measuring TT, cFT, and FAI, compared to the direct immunoassay method. WIDER IMPLICATIONS Our results directly informed the 2023 International PCOS Guideline recommendations to use TT and FT as the first-line laboratory tests to assess biochemical hyperandrogenism in the diagnosis of PCOS. cFT should be assessed by equilibrium dialysis or ammonium sulfate precipitation, or calculated using FAI. If TT or cFT are not elevated, A4 and DHEAS could also be considered, noting their poorer specificity. Laboratories should utilize LC-MS/MS for androgen measurement given its high accuracy. Future studies should focus on establishing optimal normative cut-off values in large, unselected, and ethnically diverse cohorts of women. REGISTRATION NUMBER The review protocol was prepublished in the 2023 PCOS Guideline Technical Report (https://www.monash.edu/__data/assets/pdf_file/0010/3379591/TechnicalReport-2023.pdf).

中文翻译：

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评估多囊卵巢综合征雄激素测定的诊断准确性：为循证指南提供信息的系统评价和诊断荟萃分析


背景 生化雄激素过多症是多囊卵巢综合征 （PCOS） 的标志和诊断特征。然而，在 PCOS 诊断中评估生化高雄激素血症的最准确雄激素测定方法仍不确定。客观和基本原理本系统综述旨在评估不同的雄激素指标 [包括总睾酮 （TT）、计算的游离睾酮 （cFT）、游离雄激素指数 （FAI）、雄烯二酮 （A4）、硫酸脱氢表雄酮 （DHEAS） 和二氢睾酮 （DHT）] 诊断 PCOS 女性生化高雄激素血症的准确性，为 2023 年国际 PCOS 循证指南提供信息。检索方法 为了更新2018年国际PCOS指南的证据，于2017年7月3日至2023年6月23日在Medline（Ovid）、CINAHL、所有EBM、EMBASE和PsycInfo中对评估雄激素在生化高雄激素血症诊断中的文章进行了系统检索。使用修订后的诊断准确性研究质量评估 （QUADAS-2） 来评估偏倚风险和适用性。使用 STATA 18 软件进行诊断测试准确性荟萃分析。使用双变量模型以 95% CI 计算汇总灵敏度和特异性，而分层汇总受试者工作特征 （ROC） 模型用于生成汇总 ROC 曲线。结果 在回顾的 23 项研究中，18 项被纳入荟萃分析，数据来自 2857 名参与者（1650 名 PCOS 患者和 1207 名对照组）。对于诊断 PCOS 中的生化高雄激素血症，合并敏感性、特异性和 AUC 与 95% CI 为 TT：0.74 （0.63-0.82）、0.86 （0.77-0.91） 和 0.87 （0.84-0.90）;cFT：0.89 （0.69–0.96）、0.83 （0.79–0.86） 和 0.85 （0.81–0.88）;FAI：0.78 （0.70–0.83）、0.85 （0.76–0.90） 和 0.87 （0.84–0.90）;A4：0.75 （0.60-0.86）、0.71 （0.51-0.85） 和 0.80 （0.76-0.83）;和 DHEAS：分别为 0.75 （0.61-0.85）、0.67 （0.48-0.81） 和 0.77 （0.73-0.81）。在亚组分析中，与直接免疫测定法相比，液相色谱-串联质谱法 （LC-MS/MS） 在测量 cFT、FAI、A4 和 DHEAS 方面具有更高的灵敏度，在测量 TT、cFT 和 FAI 方面具有更高的特异性。更广泛的影响 我们的结果直接为 2023 年国际 PCOS 指南建议提供信息，即使用 TT 和 FT 作为一线实验室检查来评估 PCOS 诊断中的生化高雄激素血症。cFT 应通过平衡透析或硫酸铵沉淀进行评估，或使用 FAI 计算。如果 TT 或 cFT 没有升高，也可以考虑 A4 和 DHEAS，并注意到它们的特异性较差。鉴于 LC-MS/MS 的准确度高，实验室应使用 LC-MS/MS 进行雄激素测定。未来的研究应侧重于在大型、未经选择和种族多样化的女性队列中建立最佳规范临界值。注册号 本综述方案已预先发表在 2023 年 PCOS 指南技术报告 （https://www.monash.edu/__data/assets/pdf_file/0010/3379591/TechnicalReport-2023.pdf） 中。