Establishment of PCOS-specific prolactin reference intervals to optimize laboratory demand management for macroprolactin screening

BACKGROUND AND AIM: Women with polycystic ovary syndrome (PCOS) often have elevated prolactin serum concentrations. This can lead to unnecessary macroprolactin screening and diagnostic confusion. This study aimed to establish disease-specific prolactin reference intervals in women with PCOS to optimize laboratory demand management. METHODS: A retrospective observational study was conducted between June 2022 and January 2024. Cases of confirmed macroprolactinemia were excluded beforehand. The cohort included 130 women of reproductive age (18-42 years) diagnosed with PCOS according to the 2003 Rotterdam criteria. To ensure cohort homogeneity, only patients presenting with the hyperandrogenic phenotype (biochemical hyperandrogenism) were selected. Exclusion criteria included oral contraceptive use, pregnancy, thyroid dysfunction, chronic kidney disease, and prolactin-elevating medications. Patients in the menopausal transition or with premature ovarian insufficiency (FSH > 25.8 mIU/L) were also excluded from the study. The reference intervals for prolactin serum concentrations were calculated by an indirect method based on laboratory results extracted from the Laboratory Information System (Modulab®) and using the non-parametric percentile method (2.5th and 97.5th). RESULTS: The PCOS-specific reference intervals for serum prolactin concentrations were 132.2-804.1 mIU/L. Compared to the upper reference limit of 637 mIU/L for the general population, implementing this PCOS-specific upper reference limit would have reduced the need for reflex macroprolactin testing from 13.1% (17 cases) to 2.3% (3 cases). CONCLUSION: The newly proposed reference intervals for women with the hyperandrogenic PCOS phenotype apply specifically to premenopausal women aged 18 to 42 years who are not experiencing the menopausal transition. Implementing the reference intervals obtained in this study will significantly improve laboratory demand management by reducing unnecessary reflex testing and facilitating the design of more targeted diagnostic strategies.