Development of Prediction Models Using Machine Learning Algorithms for Girls with Suspected Central Precocious Puberty: Retrospective Study

Background: Central precocious puberty (CPP) in girls seriously affects their physical and mental development in childhood. The method of diagnosis-gonadotropin-releasing hormone (GnRH)-stimulation test or GnRH analogue (GnRHa)-stimulation test-is expensive and makes patients uncomfortable due to the need for repeated blood sampling. Objective: We aimed to combine multiple CPP-related features and construct machine learning models to predict response to the GnRHa-stimulation test. Methods: In this retrospective study, we analyzed clinical and laboratory data of 1757 girls who underwent a GnRHa test in order to develop XGBoost and random forest classifiers for prediction of response to the GnRHa test. The local interpretable model-agnostic explanations (LIME) algorithm was used with the black-box classifiers to increase their interpretability. We measured sensitivity, specificity, and area under receiver operating characteristic (AUC) of the models. Results: Both the XGBoost and random forest models achieved good performance in distinguishing between positive and negative responses, with the AUC ranging from 0.88 to 0.90, sensitivity ranging from 77.91% to 77.94%, and specificity ranging from 84.32% to 87.66%. Basal serum luteinizing hormone, follicle-stimulating hormone, and insulin-like growth factor-I levels were found to be the three most important factors. In the interpretable models of LIME, the abovementioned variables made high contributions to the prediction probability. Conclusions: The prediction models we developed can help diagnose CPP and may be used as a prescreening tool before the GnRHa-stimulation test.