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