title: Influence of sex and hormone status on circulating natriuretic peptides.
abstract: OBJECTIVE
  The aim of this study was 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 N-terminal pro-B-type natriuretic peptide (NT-proBNP), total testosterone, and sex hormone-binding globulin plasma levels 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) post-menopausal women not receiving hormone replacement therapy; 3) pre-menopausal women not receiving hormonal contraceptives; 4) post-menopausal women receiving hormone replacement therapy; and 5) pre-menopausal women receiving hormonal contraceptives.
  
  
  RESULTS
  Circulating 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. Across sex/hormone status groups, 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.
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts, USA. carolyn_lam@nuhs.edu.sg
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Karen
authors.initials: K
authors.lastname: Choong
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: McCabe
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Coviello
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D045265:Natriuretic Peptides / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D017698:Postmenopause; D017697:Premenopause; D012737:Sex Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D003276:Contraceptives, Oral; D004967:Estrogens; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D012738:Sex Hormone-Binding Globulin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013739:Testosterone