Increase in circulating levels of cardiac natriuretic peptides after hormone replacement therapy in postmenopausal women

Abstract

The mechanisms that mediate the cardioprotective action of steroid hormones in postmenopausal women are poorly understood. To study the inter-relationship between female steroid hormones and cardiac natriuretic peptides, plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in postmenopausal women, both before and after oestrogen replacement therapy. A total of 22 healthy postmenopausal women (mean age 51.9+/-4.6 years) were enrolled in the study; all had been postmenopausal for at least 1 year and all reported climacteric symptoms accompanied by increased levels of follicle-stimulating hormone (>30 m-i.u./ml) and luteinizing hormone (>20 m-i.u./ml), and a reduction in oestradiol (<25 pg/ml). All women were given hormone replacement therapy with transdermal oestradiol, either patch (50 microg/24 h) or gel (1 mg/day), cyclically combined with oral dihydrogesterone (10 mg/day for 12 days/month, on days 19-30 of the month). ANP and BNP were measured directly in plasma samples with specific and sensitive immunoradiometric assays before and after hormone replacement therapy (transdermal oestradiol combined with oral dihydrogesterone). Body weight, arterial blood pressure and echocardiographic examination values did not change after hormone replacement therapy. As expected, serum oestradiol increased significantly and gonadotropins decreased as an effect of the hormone replacement therapy. On average, both ANP and BNP had increased significantly after 3 months of hormone replacement therapy [ANP: before treatment, 17.6+/-9.6 pg/ml; after, 23.6+/-5.6 pg/ml (P=0.0173); BNP: before treatment, 12.6+/-10.2 pg/ml; after, 19.8+/-14.0 pg/ml (P<0.0001)]. Our study indicates that hormone replacement therapy for a period of 3 months induces a rise in the circulating levels of cardiac natriuretic hormones in postmenopausal women. Our data also suggest the working hypothesis that cardiac natriuretic peptides may play an important role in mediating the cardioprotective effects of female steroid sex hormones in women throughout life.

Impact of Body Mass and Body Composition on Circulating Levels of Natriuretic Peptides

“…For example, androgens, which promote the development of lean mass, may suppress natriuretic peptide release, 17,18 whereas estrogens, which are associated with lower lean mass, increase natriuretic peptide levels. 19 Less likely hypotheses to explain our observations include the possibility that lean mass secretes a substance that leads to BNP and NT-proBNP degradation, or that lean mass contributes directly to BNP and NT-proBNP clearance. Further studies will be needed to confirm these findings and to explore the associated mechanisms.…”

Biomarkers in ACS and Heart Failure: Should Men and Women Be Interpreted Differently?

“…One murine-based study demonstrated that treatment with estradiol and progesterone stimulated NP gene expression in females (30 ), while another study demonstrated that testosterone suppressed volumestimulated NP release from isolated perfused rat atria (31 ). Clinically, a study of postmenopausal women demonstrated a significant increase in mean BNP concentrations after transdermal estradiol administration (32 ), while observational studies have identified inverse correlations between circulating androgens and NP concentrations (Fig. 3) (33, 34 ).…”

Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones

“…Experimental studies in animals have pointed out that female sex steroids increase ANP gene expression in a dose-dependent manner and that both estradiol and progesterone are necessary to maintain suitable levels of ANP gene expression in rat cardiomyocytes (15). Furthermore, hormone replacement therapy with female steroid hormones shows a stimulatory action on the production/secretion of CNHs in postmenopausal women (46,61).…”