Effect of Testosterone on Natriuretic Peptide Levels

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.

Published by Elsevier Inc.

Figures

Figure 1.. Changes in serum testosterone and NT-proBNP levels with respect to testosterone dose.

Changes in log serum testosterone levels (panel A) and changes in log serum NT-proBNP levels (panel B) from week 0 (baseline) to week 12 with respect to testosterone dose are displayed. NT-proBNP, N-terminal pro b-type natriuretic peptide.

Figure 2.. Conceptual Path Model: Testosterone dose impacts NT-proBNP levels through its effects on serum testosterone levels.

Higher testosterone doses led to higher serum testosterone levels at week 12 (Path A), which were associated with lower NT-proBNP levels at week 12 (Path B). The negative relationship of testosterone dose and NT-proBNP levels (Path A*B) was driven by the negative association of serum testosterone levels with NT-proBNP levels (Path B). These relationships remained significant after adjusting for age, BMI, and race. NT-proBNP, N-terminal pro b-type natriuretic peptide; SE, standard error; T, testosterone