Systematic analysis between inflammation-related index and sex hormones in American adults: cross-sectional research based NHANES 2013-2016

Abstract

Background: A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.

Methods: We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.

Results: Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m²).

Conclusion: In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

Keywords: National Health and Nutrition Examination Survey (NHANES); inflammation-related index; machine learning; sex hormones; systemic immune-inflammation index.

Figure 1

Flowchart of the research populations: NHANES 2013–2016.

Figure 2

Distribution of sex hormones and inflammation-related index among American population. (A) Male Testosterone; (B) Male Estradiol; (C) Male SHBG; (D) Female Testosterone; (E) Female Estradiol; (F) Female SHBG; (G) NC; (H) LC; (I)PLT; (J) SII; (K) PPN; (L) NLR; (M) PLR. NC PC, NC, and LC were measured in 1000 cells/uL. LC, lymphocyte count; NC, neutrophil count; NLR, neutrophil-to-lymphocyte ratio; PLT, platelet count; PLR, platelet-to-lymphocyte ratio; PPN, the product of platelet count and neutrophil count; SII, systemic immune-inflammation index.

Figure 3

Comparison of sex hormones and inflammation-related index between various gender. (A) LC; (B) NC; (C) PLT; (D) SII; (E) PLR; (F) NLR; (G) PPN; (H) Testosterone; (I) Estradiol; (J) SHBG; (K) FAI; (L) TT/E₂. *** mean p < 0.0001.

Figure 4

Linear and Non-linear relationship between inflammation-related index and sex hormones among American male. (A) TT and SII; (B) E₂ and SII; (C) SHBG and SII; (D) FAI and SII; (E) TT/E₂ and SII; (F) TT and NLR; (G) E₂ and NLR; (H) SHBG and NLR; (I) FAI and NLR; (J) TT/E₂ and NLR; (K) TT and PLR; (L) E₂ and NLR; (M) SHBG and NLR; (N) FAI and NLR; (O) TT/E₂ and NLR; (P) TT and PPN; (Q) E₂ and PPN; (R) SHGB and PPN; (S) FAI and PPN; (T) TT/E₂ and PPN; (U) TT and LC; (V) E₂ and LC; (W) SHBG and LC; (X) FAI and LC; (Y) TT/E₂ and LC; (Z) TT and NC; (AA) E2 and NC; (BB) SHBG and NC; (CC) FAI and NC; (DD) TT/E2 and NC; (EE) TT and PLT; (FF) E2 and PLT; (GG) SHBG and PLT; (HH) FAI and PLT; (II) TT/E2 and PLT; SII, PLR, NLR, PPN, PC, NC, and LC were considered continuous variables and conducted log2 conversion. Generalized-linear models adjusts for age, race, education, marital status, family income to poverty ratio, body mass index (kg/m²), smoking and drinking. TT, Testosterone; E₂, Estradiol; SHBG, sex hormone-binding globulin; FAI, free androgen index; LC, lymphocyte count; NC, neutrophil count; NLR, neutrophil-to-lymphocyte ratio; PLT, platelet count; PLR, platelet-to-lymphocyte ratio; PPN, the product of platelet count and neutrophil count; SII, systemic immune-inflammation index.

Figure 5

Linear and Non-linear relationship between inflammation-related index and sex hormones among American female. (A) TT and SII; (B) E₂ and SII; (C) SHBG and SII; (D) FAI and SII; (E) TT/E₂ and SII; (F) TT and NLR; (G) E₂ and NLR; (H) SHBG and NLR; (I) FAI and NLR; (J) TT/E₂ and NLR; (K) TT and PLR; (L) E₂ and NLR; (M) SHBG and NLR; (N) FAI and NLR; (O) TT/E₂ and NLR; (P) TT and PPN; (Q) E₂ and PPN; (R) SHGB and PPN; (S) FAI and PPN; (T) TT/E₂ and PPN; (U) TT and LC; (V) E₂ and LC; (W) SHBG and LC; (X) FAI and LC; (Y) TT/E₂ and LC; (Z) TT and NC; (AA) E2 and NC; (BB) SHBG and NC; (CC) FAI and NC; (DD) TT/E2 and NC; (EE) TT and PLT; (FF) E2 and PLT; (GG) SHBG and PLT; (HH) FAI and PLT; (II) TT/E2 and PLT; SII, PLR, NLR, PPN, PC, NC, and LC were considered continuous variables and conducted log2 conversion. Generalized-linear models adjusts for age, race, education, marital status, family income to poverty ratio, body mass index (kg/m²), smoking and drinking. TT, Testosterone; E₂, Estradiol; SHBG, sex hormone-binding globulin; FAI, free androgen index; LC, lymphocyte count; NC, neutrophil count; NLR, neutrophil-to-lymphocyte ratio; PLT, platelet count; PLR, platelet-to-lymphocyte ratio; PPN, the product of platelet count and neutrophil count; SII, systemic immune-inflammation index.

Figure 6

XGBoost models indicate the corresponding variable importance score of the inflammation-related indexes on sex hormones. (A) Testosterone in male; (B) Estradiol in male; (C) SHBG in male; (D) FAI in male; (E) TT/E₂ in male; (F) Testosterone in female; (G) Estradiol in female; (H) SHBG in female; (I) FAI in female; (J) TT/E₂ in female; The X-axis indicates the importance score, the relative number of a variable used to distribute the data; the Y-axis shows the Inflammation-related Index.