Association of different inflammatory indices with risk of early natural menopause: a cross-sectional analysis of the NHANES 2013-2018

Abstract

Background: Early natural menopause, characterized by the cessation of ovarian function before the age of 45, has been a subject of prior research indicating that inflammation may predict the onset of menopause. However, the specific relationship between peripheral blood inflammatory parameters and early natural menopause remains ambiguous.

Methods: This observational study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2013-2018. The age at menopause was ascertained through the Reproductive Health Questionnaire (RHQ), with early natural menopause defined as menopause occurring before the age of 45 years. Complete blood counts were derived from laboratory test data, and seven indices of inflammation were calculated, including lymphocyte count (LC), neutrophil count (NC), systemic immune inflammation index (SII), product of platelet and neutrophil count (PPN), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). A multivariate weighted logistic regression analysis was employed to estimate the association between these inflammatory indices and early natural menopause.

Results: A total of 2,034 participants were included in the analysis, of whom 460 reported experiencing menopause before the age of 45. Both Log2-NC and Log2-PPN were found to be positively correlated with early menopause, with odds ratios (OR) of 1.56 (95% CI: 1.16, 2.09; p = 0.005) and 1.36 (95% CI: 1.07, 1.72; p = 0.015), respectively. The results from models 1 and 2 were consistent with those from model 3. In the trend test, participants in the fourth quartile (Q4) of log2-LC exhibited a positive correlation with early menopause compared to those in the lowest quartile (Q1), with an OR of 1.41 (95% CI: 1.03, 1.93; p = 0.033). Similarly, the fourth quartile (Q4) of log2-NC and log2-PPN demonstrated a positive correlation with early menopause, with odds ratios (OR) of 1.76 (95% CI: 1.27-2.45; p < 0.001) and 1.66 (95% CI: 1.21-2.29; p = 0.002), respectively. In Model 3, log2-SII, log2-PLR, log2-NLR, and log2-LMR were not significantly associated with early menopause.

Conclusion: Our findings indicate that elevated levels of Log2-LC, Log2-NC, and Log2-PPN are positively correlated with an increased risk of early menopause among women in the United States.

Keywords: NHANES; cross-sectional study; early natural menopause; inflammatory indices; peripheral blood cell counts.

Figure 1

Flowchart of the research populations: NHANES 2013–2018.

Figure 2

Restricted cubic spline plot of the association between inflammatory indices and early menopause. The model was adjusted for race, marital status, education level, Income-to-poverty ratio (PIR), Body mass index (BMI), smoking status, alcohol use, infertility, pelvic inflammatory disease (PID), number of pregnancies, number of live births, age at menarche, history of diabetes, hypertension, high cholesterol levels, and cancer.

Figure 3

Subgroup analyses for the relationship between different inflammatory indices and early menopause. A: Log2-LC. B: Log2-NC. C: Log2-PPN. The model was adjusted for race, marital status, education level, Income -to -poverty ratio (PIR), Body mass index (BMI), smoking status, alcohol use, infertility, pelvic inflammatory disease (PID), number of pregnancies, number of live births, age at menarche, history of diabetes, hypertension, high cholesterol levels, and cancer.