Sex steroids, sex hormone-binding globulin and levels of N-terminal pro-brain natriuretic peptide in postmenopausal women

Abstract

Background: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) has a well-documented prognostic value for cardiovascular disease and sex-hormones are suggested to modulate NT-proBNP levels.

Objective: To examine whether endogenous sex-hormones and sex hormone-binding globulin (SHBG) are associated with NT-proBNP levels in postmenopausal women free of clinical cardiovascular diseases.

Methods: Total estradiol (E₂), total testosterone (TT), androstenedione (AD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and NT-proBNP were assessed in 4112 postmenopausal women free of cardiovascular diseases from the prospective population-based Rotterdam Study. Free androgen index (FAI) was calculated as ratio of TT to SHBG concentration. TT, AD, DHEA(S), SHBG, FAI and NT-proBNP were natural log transformed. Regression coefficients and 95% Confidence Intervals (CI) were calculated using multivariable linear regression models adjusting for confounders.

Results: In models adjusted for multiple confounders (age, reproductive, life style and cardiovascular risk factors) higher SHBG (per 1 SD increase, β = 0.15, 95% CI = 0.12, 0.18), and lower levels of TT (per 1 SD increase, β = -0.05, 95%CI = -0.08, -0.02), FAI (per 1 SD increase, β = -0.13, 95%CI = -0.15, -0.09), DHEAS (per 1 SD increase, β = -0.06, 95% CI = -0.09, -0.04) and DHEA (per 1 SD increase, β = -0.06, 95%CI = -0.09, -0.04) were associated with higher levels of NT-proBNP. However, no consistent association was found between E₂ and AD and NT-proBNP levels. Additionally, stratification by BMI did not affect any of observed associations.

Conclusion: Our findings support the hypothesis that higher androgens might be associated with lower natriuretic peptide levels in postmenopausal women.

Keywords: Endogenous sex hormones; Menopause; NT-pro-BNP; Natriuretic peptides; Postmenopausal women.