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

Context: 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.

Objective: We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S. adult women who were free of diabetes.

Methods: 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.

Results: 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.

Conclusion: 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.