Association of Age at Menarche with Inflammation and Glucose Metabolism Biomarkers in U.S. Adult Women: NHANES 1999-2018.

Abstract

Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown. We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S. adult women who were free of diabetes. Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19,228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. CRP, fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers. The median age at the time of blood sample collection was 44 years (IQR, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend=0.006); fasting glucose (P-trend<0.0001); fasting insulin (P-trend <0.0001); and ferritin (p-trend<0.0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (p-interaction = 0.014), fasting insulin (p-interaction <0.001), and fasting glucose (p-interaction<0.001). In stratified analysis, the observed associations became more pronounced in non-smokers, while they were attenuated to non-significance in active smokers. Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among non-smokers.