Influence of Sex and Hormone Status on Circulating Natriuretic Peptides
Key result
Circulating NT-proBNP was strongly associated with sex and hormone status, with men having lower levels than women and women receiving hormonal contraceptives having higher levels than those not receiving hormone therapy.
Why the study?
Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear.
Does sex and hormone status influence circulating NT-proBNP levels in community-based adults?
Key Points
- To assess the relationship between sex hormones, exogenous hormone therapies, and circulating natriuretic peptide levels in community-based adults.
- Measured plasma NT-proBNP, total testosterone, and sex hormone binding globulin (SHBG) in N=4,056 men and women (mean age 40±9 years) from the Framingham Heart Study Third Generation cohort.
- Categorized participants into five sex/hormone status groups: men, postmenopausal women not receiving HRT, premenopausal women not receiving hormonal contraceptives, postmenopausal women receiving HRT, and premenopausal women receiving hormonal contraceptives.
- Circulating NT-proBNP differed by sex/hormone status (overall P<0.0001); men had lower levels than women in all groups, and women receiving hormonal contraceptives had higher levels than non-users (all P<0.0001).
- NT-proBNP decreased across increasing quartiles of free testosterone in men (P for trend<0.01) and women (P for trend<0.0001); each unit increase in log free testosterone was associated with a 20% decrease in NT-proBNP among women (P<0.0001).
- Sex/hormone status explained 38% of the multivariable variability in NT-proBNP, but this attenuated to 1% after adding log free testosterone to the model.
Study Design
Type
Cross-Sectional (n=4,056)
Structured PICO
Does sex and hormone status influence circulating NT-proBNP levels in community-based adults?
P
Population
4,056 community-based adults (mean age 40, 53% female) from the Framingham Heart Study Third Generation cohort, free of prevalent heart failure or MI.
E
Exposure
Sex and hormone status (men, postmenopausal women without HRT, premenopausal women without HC, postmenopausal women with HRT, premenopausal women with HC)
C
Comparator
Comparisons across the 5 sex/hormone status groups
O
Outcome
Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levelssurrogate
Main Result
p-value: p=<0.0001
Limitations
- Measurements of estrogens and details regarding individual hormone components of HC were not available
- Free testosterone was estimated rather than directly measured
- Potential for residual confounding by unmeasured co-morbidities
- Observational design limits causal conclusions
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Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“They are the heart's protective hormones. So why is it that high levels are bad?”
“NT-proBNP levels are lowest in men and highest in pre-menopausal women on contraceptives”
Implication
Differences in free testosterone may largely explain the sex- and hormone-related differences in circulating natriuretic peptides, with androgens appearing to suppress NT-proBNP.
Abstract
Objectives To assess the relationship between sex hormones and natriuretic peptide levels in community-based adults Background Women have higher circulating natriuretic peptide concentrations than men, but the mechanisms for these sex-related differences and the impact of hormone therapy are unclear. Experimental studies suggest that androgens may suppress natriuretic peptide secretion. Methods We measured plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone binding globulin (SHBG) 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 Circulating NT-proBNP was associated with sex/hormone status (overall P<0.0001). Men had lower NT-proBNP than women of all menopause or hormone groups, and women receiving hormonal contraceptives had higher NT-proBNP 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. Across sex/hormone status groups, FT decreased and SHBG increased in tandem with increasing NT-proBNP. In sex-specific analyses, NT-proBNP decreased across increasing quartiles of free testosterone in men (P for trend<0.01) and in 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 circulating androgens and the potentiating effect of exogenous female hormone therapy contribute to the higher circulating NT-proBNP concentrations in women.
Discussion
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Cite This Study
Lam et al. (2011) conducted a cross-sectional in Community-based adults (n=4,056). Sex and hormone status vs. Other sex/hormone status groups was evaluated on Circulating NT-proBNP concentrations (p=<0.0001). Circulating NT-proBNP was strongly associated with sex and hormone status, with men having lower levels than women and women receiving hormonal contraceptives having higher levels than those not receiving hormone therapy.