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EXPEDITED REVIEW

Associations Among Androgens, Estrogens, and Natriuretic Peptides in Young Women

Observations From the Dallas Heart Study

The Donald W. Reynolds Cardiovascular Clinical Research Center and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

Manuscript received July 27, 2006; revised manuscript received September 19, 2006, accepted October 18, 2006.

^_* Reprint requests and correspondence: Dr. Alice Y. Chang, University of Texas Southwestern Medical School, MC 9066, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9066. (Email: alice.chang{at}utsouthwestern.edu).

OBJECTIVES: We sought to determine if natriuretic peptides are associated with estrogen and androgen status in a population study of young women without known cardiac disease.

BACKGROUND: Circulating concentrations of plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are higher in women than in men, and they may be influenced by estrogens and androgens.

METHODS: Cardiac magnetic resonance imaging, dual energy X-ray absorbtiometry, and measurements of BNP, NT-proBNP, follicle-stimulating hormone (FSH), total testosterone, and sex hormone-binding globulin (SHBG), were performed in 682 women (ages 35 to 49 years) participating in the Dallas Heart Study.

RESULTS: In multivariable analyses adjusting for age, race/ethnicity, body mass index (BMI), serum creatinine, left ventricular mass and left ventricular ejection fraction <55%, menopausal status, and FSH were not associated with BNP and NT-proBNP. In contrast, higher SHBG was associated with higher BNP and NT-proBNP, while the free androgen index and calculated free testosterone were inversely associated with BNP and NT-proBNP (p < 0.0001 for each). Addition of SHBG or any measure of free testosterone to the multivariable models modified the effect of BMI and lean mass, such that measures of body composition were no longer significantly associated with BNP or NT-proBNP.

CONCLUSIONS: Among young women, measures of free testosterone were independently and inversely associated with BNP and NT-proBNP. These results suggest that circulating free testosterone, not estradiol, mediates gender differences in natriuretic peptides. In addition, the association between higher BMI and lean body mass with natriuretic peptides may be mediated by testosterone.

Abbreviations and Acronyms   BMI = body mass index   BNP = B-type natriuretic peptide   cFT = calculated free testosterone   DEXA = dual energy X-ray absorbtiometry   FAI = free androgen index   FSH = follicle-stimulating hormone   LVH = left ventricular hypertrophy   MRI = magnetic resonance imaging   NT-proBNP = N-terminal pro-B-type natriuretic peptide   SHBG = sex hormone-binding globulin   TT = total testosterone

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