Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China.
Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210008, China; Department of Pharmacy, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210000, China.
J Steroid Biochem Mol Biol. 2025 Jan;245:106626. doi: 10.1016/j.jsbmb.2024.106626. Epub 2024 Oct 23.
Polycystic ovary syndrome (PCOS) is a metabolic disorder with clinical heterogeneity. PCOS women with non-hyperandrogenemia (NA) might be misdiagnosed due to a lack of diagnostic markers. This study aims to systematically analyze the differences in steroid hormones between PCOS women with hyperandrogenemia (HA) and NA, and to screen classification diagnosis models for PCOS. The serum samples from 54 HA-PCOS, 79 NA-PCOS and 60 control women (Non-PCOS) aged between 18 and 35 were measured by an integrated steroid hormone-targeted quantification assay using LC-MS/MS. The levels of serum androgens, corticosteroids, progestins and estrogens in the steroid hormone biosynthesis pathway were analyzed in PCOS and Non-PCOS women. Eight machine learning methods including Linear Discriminant Analysis (LDA), K-nearest Neighbors (KNN), Boosted Logistic Regression (LogitBoost), Naive Bayes (NB), C5.0 algorithm (C5), Random Forest (RF), Support Vector Machines (SVM), and Neural Network (NNET) were performed, evaluated and selected for classification diagnosis of PCOS. A 10-fold cross-validation on the training set was performed. The whole metabolic flux from cholesterol to downstream steroid hormones increased significantly in PCOS, especially in HA-POCS women. The RF model was chosen for the classification diagnosis of HA-PCOS, NA-PCOS, and Non-PCOS women due to the maximum average accuracy (0.938, p<0.001), AUC (0.989, p<0.001), and kappa (0.906, p<0.001), and the minimum logLoss (0.200, p<0.001). Five steroid hormones including testosterone, androstenedione, total 2-methoxyestradiol, total 4-methoxyestradiol, and free estrone were selected as the decision trees for the simplified RF model. A total of 37 women were included in the validation set. The diagnostic sensitivity for HA-PCOS, NA-PCOS, and Non-PCOS was 100 %, 93.3 % and 91.7 %, respectively. HA-PCOS, NA-PCOS, and Non-PCOS women showed obvious different steroid hormone profiles. The simplified RF model based on two androgens and three estrogens could be effectively applied to the classification diagnosis of PCOS, further reducing the missed diagnosis rate of NA-PCOS.
多囊卵巢综合征（PCOS）是一种具有临床异质性的代谢紊乱。由于缺乏诊断标志物，非高雄激素血症（NA）的 PCOS 女性可能会被误诊。本研究旨在系统分析高雄激素血症（HA）和 NA 的 PCOS 女性之间类固醇激素的差异，并筛选 PCOS 的分类诊断模型。采用 LC-MS/MS 对 54 例 HA-PCOS、79 例 NA-PCOS 和 60 例对照（非 PCOS）女性（年龄 18-35 岁）的血清样本进行了整合的类固醇激素靶向定量分析。分析了 PCOS 和非 PCOS 女性类固醇激素生物合成途径中的血清雄激素、皮质类固醇、孕激素和雌激素水平。采用线性判别分析（LDA）、K-最近邻（KNN）、增强型逻辑回归（LogitBoost）、朴素贝叶斯（NB）、C5.0 算法（C5）、随机森林（RF）、支持向量机（SVM）和神经网络（NNET）等 8 种机器学习方法进行了分类诊断，并进行了评估和选择。在训练集上进行了 10 折交叉验证。胆固醇到下游类固醇激素的整个代谢通量在 PCOS 中显著增加，尤其是在 HA-POCS 女性中。由于平均准确度最高（0.938，p<0.001）、AUC（0.989，p<0.001）和 Kappa（0.906，p<0.001），以及最小的对数损失（0.200，p<0.001），因此选择 RF 模型用于 HA-PCOS、NA-PCOS 和非 PCOS 女性的分类诊断。睾酮、雄烯二酮、总 2-甲氧基雌二醇、总 4-甲氧基雌二醇和游离雌酮等 5 种类固醇激素被选为简化 RF 模型的决策树。验证集共纳入 37 例女性。HA-PCOS、NA-PCOS 和非 PCOS 的诊断灵敏度分别为 100%、93.3%和 91.7%。HA-PCOS、NA-PCOS 和非 PCOS 女性表现出明显不同的类固醇激素谱。基于两种雄激素和三种雌激素的简化 RF 模型可有效应用于 PCOS 的分类诊断，进一步降低 NA-PCOS 的漏诊率。
