Influence of Sex and Hormone Status on Circulating Natriuretic Peptides

Study Questions:

What is the effect of sex and hormone status on circulating levels of natriuretic peptides (NPs)?

Methods:

N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone–binding globulin plasma levels were measured in 4,056 men and women (mean age 40 ± 9 years) from the Framingham Heart Study Third-Generation cohort. Sex/hormone status was grouped as: 1) men; 2) postmenopausal women not receiving hormone replacement therapy; 3) premenopausal women not receiving hormonal contraceptives; 4) postmenopausal women receiving hormone replacement therapy; and 5) premenopausal women receiving hormonal contraceptives.

Results:

NT-proBNP levels were associated with sex/hormone status (overall p < 0.0001). Men had lower NT-proBNP levels than women of all menopause or hormone groups, and women receiving hormonal contraceptives had higher NT-proBNP levels than women who were not receiving hormone therapy (all p < 0.0001). These relationships remained significant after adjusting for age, body mass index, and cardiovascular risk factors. Free testosterone (FT) levels decreased and sex hormone–binding globulin levels increased in tandem with increasing NT-proBNP levels. In sex-specific analyses, NT-proBNP levels decreased across increasing quartiles of FT in men (p for trend < 0.01) and women (p for trend < 0.0001). Adjustment for FT markedly attenuated the association between sex/hormone status and NT-proBNP concentrations.

Conclusions:

These findings suggest that lower levels of circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP concentrations in women.

Perspective:

NT-proBNP levels are higher in women than in men. Since NT-proBNP levels may serve as a biomarker or mediator of cardiovascular diseases, it is important to understand the underlying mechanism(s) responsible for the differences in NT-proBNP levels between sexes. Whether the effects of sex/hormones on NT-proBNP levels demonstrated in this study are related to differences in cardiovascular risk between the sexes will require further study.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Contraceptive Agents, Risk Factors, Sex Hormone-Binding Globulin, Heart Diseases, Menopause, Natriuretic Peptides, Potassium, Body Mass Index, Biological Markers, Cesium, Gonadal Steroid Hormones, Heart Failure, Cardiovascular Diseases, Premenopause, Hormone Replacement Therapy, Atrial Natriuretic Factor, Natriuretic Peptide, Brain, Testosterone


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