Effect size and inferential statistical techniques coupled with machine learning for assessing the association between prolactin concentration and metabolic homeostasis

Background and objective: Recent guidelines classify low prolactin levels as low as <7 ng/mL and high levels as >25 ng/mL, while the "Homeostatically Functionally Increased Transient Prolactinemia" (HomeoFIT-PRL) range (25-100 ng/mL) suggests that a temporary increase in prolactin could be metabolically beneficial if no related health issues are present. The aim of this study was to investigate the association between mean prolactin concentrations and disturbances in glycidic and lipidic metabolism and to identify the gray zone associated with prolactin inflection points that correlate with these metabolic changes.Methods: This cross-sectional study involved 65,795 adults who underwent HOMA-IR, glucose, insulin, total cholesterol, HDL-c, LDL-c, and triglyceride tests. Data was categorized into 106 partitions based on prolactin results. Employing an approach referred to in this study as "Hierarchical Multicriteria Analysis of Differences Between Groups -Statistical and Effect Size Approach" (HiMADiG-SESA) comparing the mean concentrations of metabolic tests across prolactin ranges. A machine learning model was utilized to determine inflection points and their corresponding confidence intervals (CIs). These CIs helped establish gray zones in mean prolactin results related to metabolic changes.Results: Statistically and clinically, metabolic test means differed for prolactin <7 ng/mL, except insulin. In the HomeoFIT-PRL range, means were lower except for HDL-c. The gray zones of the mean prolactin results asso-ciated with changes in glycidic and lipidic metabolism were 9.58-12.87 ng/mL and 13.81-18.73 ng/mL, respectively.Conclusion: A strong correlation was identified between mean prolactin concentrations and the results of metabolism tests below the gray zones associated with inflection points, indicating the potential role of prolactin in the appearance of metabolic disorders. Mean prolactin results can provide deeper insight into metabolic balance.