Associations between levels of sex steroid hormones and inflammatory cytokines by hormone replacement therapy (HRT) status in ethnic minority postmenopausal women

ObjectiveElevated levels of inflammatory markers have been associated with metabolic diseases such as type 2 diabetes (DM) and cardiovascular disease. Inflammation associated with aging may be mediated by changes in hormonal milieu, as seen with menopause. Whether HRT modifies the relationships between levels of sex hormones and inflammatory cytokines is largely unknown, especially in minority women.DesignCross-sectional.Materials and MethodsAmong 82,069 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study, we selected 1791 ethnic minority women who were apparently healthy at baseline for a nested case-control study of DM. We examined the relationships between baseline levels of sex hormones (total estradiol [E2], total testosterone [TT], and sex hormone-binding globulin [SHBG]) and inflammatory markers (CRP, IL-6, and TNF-α), and assessed whether these associations were modified by HRT. All hormone levels were log transformed.ResultsE2 levels were directly associated with CRP levels in the entire cohort (β=0.29, P<0.0001), even after adjusting for potential confounding factors including DM status, BMI, and levels of insulin, IL-6, and TNF-α. A weak, but significant negative association was found between TT and TNF-α in current users of HRT (β=-0.04, P=0.04), persisting when controlling for potential confounders. Higher SHBG levels were associated with lower levels of CRP in women who had never used HRT (β=-0.47, P<0.0001), and in past users (β=-0.38, P=0.04), but not in current users of HRT (β=-0.02, P=0.86). Higher SHBG levels were associated with lower IL-6 levels in the entire cohort (β=-0.18, P<0.0001).ConclusionHRT did not modify the relationship between E2 and inflammatory marker levels, but it did modify the associations for TT and SHBG in relation to inflammatory markers. The inverse association between levels of CRP and SHBG only held in non-users of HRT. ObjectiveElevated levels of inflammatory markers have been associated with metabolic diseases such as type 2 diabetes (DM) and cardiovascular disease. Inflammation associated with aging may be mediated by changes in hormonal milieu, as seen with menopause. Whether HRT modifies the relationships between levels of sex hormones and inflammatory cytokines is largely unknown, especially in minority women. Elevated levels of inflammatory markers have been associated with metabolic diseases such as type 2 diabetes (DM) and cardiovascular disease. Inflammation associated with aging may be mediated by changes in hormonal milieu, as seen with menopause. Whether HRT modifies the relationships between levels of sex hormones and inflammatory cytokines is largely unknown, especially in minority women. DesignCross-sectional. Cross-sectional. Materials and MethodsAmong 82,069 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study, we selected 1791 ethnic minority women who were apparently healthy at baseline for a nested case-control study of DM. We examined the relationships between baseline levels of sex hormones (total estradiol [E2], total testosterone [TT], and sex hormone-binding globulin [SHBG]) and inflammatory markers (CRP, IL-6, and TNF-α), and assessed whether these associations were modified by HRT. All hormone levels were log transformed. Among 82,069 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study, we selected 1791 ethnic minority women who were apparently healthy at baseline for a nested case-control study of DM. We examined the relationships between baseline levels of sex hormones (total estradiol [E2], total testosterone [TT], and sex hormone-binding globulin [SHBG]) and inflammatory markers (CRP, IL-6, and TNF-α), and assessed whether these associations were modified by HRT. All hormone levels were log transformed. ResultsE2 levels were directly associated with CRP levels in the entire cohort (β=0.29, P<0.0001), even after adjusting for potential confounding factors including DM status, BMI, and levels of insulin, IL-6, and TNF-α. A weak, but significant negative association was found between TT and TNF-α in current users of HRT (β=-0.04, P=0.04), persisting when controlling for potential confounders. Higher SHBG levels were associated with lower levels of CRP in women who had never used HRT (β=-0.47, P<0.0001), and in past users (β=-0.38, P=0.04), but not in current users of HRT (β=-0.02, P=0.86). Higher SHBG levels were associated with lower IL-6 levels in the entire cohort (β=-0.18, P<0.0001). E2 levels were directly associated with CRP levels in the entire cohort (β=0.29, P<0.0001), even after adjusting for potential confounding factors including DM status, BMI, and levels of insulin, IL-6, and TNF-α. A weak, but significant negative association was found between TT and TNF-α in current users of HRT (β=-0.04, P=0.04), persisting when controlling for potential confounders. Higher SHBG levels were associated with lower levels of CRP in women who had never used HRT (β=-0.47, P<0.0001), and in past users (β=-0.38, P=0.04), but not in current users of HRT (β=-0.02, P=0.86). Higher SHBG levels were associated with lower IL-6 levels in the entire cohort (β=-0.18, P<0.0001). ConclusionHRT did not modify the relationship between E2 and inflammatory marker levels, but it did modify the associations for TT and SHBG in relation to inflammatory markers. The inverse association between levels of CRP and SHBG only held in non-users of HRT. HRT did not modify the relationship between E2 and inflammatory marker levels, but it did modify the associations for TT and SHBG in relation to inflammatory markers. The inverse association between levels of CRP and SHBG only held in non-users of HRT.