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CBC-derived leukocyte differential indices in relation to insulin resistance in women with polycystic ovary syndrome: a cross- sectional study

Piorkowska, N. J.; Bizon, A.; Bizon, K.; Franik, G.; Jonczyk, K.

2025-12-27 endocrinology
10.64898/2025.12.23.25342888 medRxiv
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ContextPolycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and frequent metabolic disturbances, including insulin resistance (IR), and is commonly accompanied by chronic low-grade inflammation. Complete blood count (CBC)-derived indices provide inexpensive markers reflecting systemic inflammatory and hematologic status; however, their relationships with androgen-related features in PCOS remain incompletely characterized. ObjectiveTo evaluate associations between androgen-related biomarkers and CBC-derived indices in young women with PCOS and to determine whether these associations persist after accounting for insulin resistance. DesignCross-sectional observational study. SettingSingle-center Gynecological Endocrinology Clinic in Katowice, Poland. ParticipantsWomen aged 16-25 years diagnosed with PCOS (Rotterdam criteria) between 2018 and 2025 (N = 1,300). Available-case and complete-case analyses were performed. Main Outcome MeasuresNeutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR). Associations with free androgen index (FAI), total testosterone, and dehydroepiandrosterone sulfate (DHEAS) were assessed using Spearman correlation and multivariable linear regression models adjusted for age and log-transformed HOMA-IR with heteroskedasticity-consistent (HC3) standard errors. False discovery rate (FDR) correction was applied. ResultsFAI was positively associated with NLR in both available-case and complete-case analyses (Spearman {rho} = 0.201; FDR-adjusted q < 0.001). DHEAS showed a positive association with NLR in complete-case analysis (q = 0.040). In multivariable models adjusted for age and log(HOMA-IR) (n = 885-888 depending on outcome), higher FAI was independently associated with lower RDW ({beta} = -0.075; 95% CI -0.141 to -0.009; q = 0.032) and lower PLR ({beta} = -2.37; 95% CI -4.60 to -0.14; q = 0.042). Higher DHEAS was independently associated with lower RDW ({beta} = -0.00056; 95% CI -0.00109 to -0.00004; q = 0.042). In complete-case analysis, total testosterone was inversely associated with PLR ({beta} = -3.91; 95% CI -7.58 to -0.24; q = 0.038). Associations between androgen markers and NLR were attenuated after adjustment. ConclusionsAmong young women with PCOS, androgen-related biomarkers are independently associated with selected CBC-derived indices, particularly RDW and PLR, whereas associations with NLR appear partly explained by shared metabolic correlates. These findings suggest that androgen excess may be linked to subtle hematologic alterations in early-stage PCOS beyond insulin resistance.

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