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J Am Coll Cardiol. 2019 Mar 26;73(11):1288-1296. doi: 10.1016/j.jacc.2018.12.062.

Effect of Testosterone on Natriuretic Peptide Levels.

Author information

1
Veterans Administration Tennessee Valley Healthcare System, Nashville, Tennessee; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: Katherine.n.bachmann@vanderbilt.edu.
2
Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
3
Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts.
4
Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
5
Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
6
Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
7
Endocrine Unit, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.

Abstract

BACKGROUND:

Circulating natriuretic peptide (NP) levels are markedly lower in healthy men than women. A relative NP deficiency in men could contribute to their higher risk of hypertension and cardiovascular disease. Epidemiological studies suggest testosterone may contribute to sex-specific NP differences.

OBJECTIVES:

This study aimed to determine the effect of testosterone administration on NP levels using a randomized, placebo-controlled design.

METHODS:

One hundred and fifty-one healthy men (20 to 50 years of age) received goserelin acetate to suppress endogenous production of gonadal steroids, and anastrazole to suppress conversion of testosterone to estradiol. Subjects were randomized to placebo gel or 4 different doses of testosterone (1%) gel for 12 weeks. Serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) and total testosterone levels were measured at baseline and follow-up.

RESULTS:

Men who did not receive testosterone replacement (placebo gel group) after suppression of endogenous gonadal steroid production experienced a profound decrease in serum testosterone (median 540 to 36 ng/dl; p < 0.0001). This was accompanied by an increase in median NT-proBNP (+8 pg/ml; p = 0.02). Each 1-g increase in testosterone dose was associated with a 4.3% lower NT-proBNP at follow-up (95% confidence interval: -7.9% to -0.45%; p = 0.029). An individual whose serum testosterone decreased by 500 ng/dl had a 26% higher predicted follow-up NT-proBNP than someone whose serum testosterone remained constant.

CONCLUSIONS:

Suppression of testosterone production in men led to increases in circulating NT-proBNP, which were attenuated by testosterone replacement. Inhibition of NP production by testosterone may partly explain the lower NP levels in men. (Dose-Response of Gonadal Steroids and Bone Turnover in Men; NCT00114114).

KEYWORDS:

BNP; NT-proBNP; cardiovascular risk; hypertension; natriuretic peptide; testosterone

PMID:
30898204
PMCID:
PMC6588352
[Available on 2020-03-26]
DOI:
10.1016/j.jacc.2018.12.062

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