Hormonal replacement therapy affects calcitonin gene-related peptide and atrial natriuretic peptide secretion in postmenopausal women

Abstract

Objective: Menopause is associated with critical changes in the cardiovascular system, and the possible effect of hormonal replacement therapy (HRT) on these changes is under investigation. The aim of our study was to evaluate in postmenopausal women the effects of HRT and clonidine on the response of plasma calcitonin gene-related peptide (CGRP) and plasma atrial natriuretic peptide (ANP) to the upright posture test and the saline infusion test respectively. Methods: CGRP and ANP levels were measured with specific radioimmunological assays and expressed in pmol/l (meansϮS.E.M). Design: Postmenopausal women (age 46-53 years) (n=18) were studied before and after 3 months of HRT (n=13) or clonidine treatment (n=5). Results: After HRT or clonidine treatment plasma CGRP levels (14·9Ϯ1·6 and 15·9Ϯ3·8 pmol/l) were significantly higher than before (9·8Ϯ0·6 and 10·5Ϯ1·6 pmol/l) (P<0·01). The assumption of upright posture caused no change in plasma CGRP levels before treatment, while after HRT, but not after clonidine treatment, an increase in plasma CGRP levels was observed (P<0·01 at 5 and 20 min). Basal plasma ANP levels significantly decreased after both HRT and clonidine treatment (P<0·01). In untreated women the saline infusion test did not induce any change in plasma ANP levels; a significant response to the test was restored after HRT but not after clonidine treatment (P<0·01 at 90 and 120 min). Conclusions:The results show that some of the adaptive responses modified by menopausal changes are restored by HRT but not clonidine treatment, suggesting a modulatory role for sex steroid hormones in cardiovascular function and salt and water balance. European Journal of Endocrinology 137 664-669

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

“…One study [22] reported no significant increase in ANP levels in 17 postmenopausal women during hormone replacement treatment. Another study [21] found a significant decrease in 13 postmenopausal women after 3 months of hormone replacement therapy. At present, it is difficult to explain these conflicting results.…”

“…At present, it is difficult to explain these conflicting results. However, these two studies [21,22] and ours used different experimental protocols (with regard to both sample collection and drugs administered) as well as assay methods (RIA compared with IRMA). To our knowledge, no previous study has examined the effects of hormone replacement therapy on circulating levels of BNP.…”

“…In some studies [17,20], circulating levels of cardiac natriuretic peptides were found to be significantly higher during the follicular than the luteal phase of the menstrual cycle, whereas in other studies [10,16,18,19] no differences were observed. Conflicting results were also obtained when ANP levels were measured in postmenopausal women before and after hormone replacement therapy : in one study [21] a significant decrease was found, while in another no significant variations were reported [22]. Finally, the plasma ANP level increased significantly in premenopausal women after administration of low-dose oral contraceptives [22].…”

Calcitonin Gene-Related Peptide during Sweating in Young Healthy Women

“…Median and percentiles (25th-75th%) of CGRP cortisol and prolactin in plasma may be a specifi c mediator of hot fl ushes [7][8][9] . Increased CGRP levels during fl ushes have been shown, as well as different basal levels in climacteric women with and without vasomotor symptoms [7][8][9]22] . The relation between CGRP and variable estrogen levels is also supported by studies, showing a modifi cation of CGRP levels by hormone replacement therapy [22] and an increase in CGRP levels during pregnancy as well as in women using oral contraceptives [23] .…”

“…Increased CGRP levels during fl ushes have been shown, as well as different basal levels in climacteric women with and without vasomotor symptoms [7][8][9]22] . The relation between CGRP and variable estrogen levels is also supported by studies, showing a modifi cation of CGRP levels by hormone replacement therapy [22] and an increase in CGRP levels during pregnancy as well as in women using oral contraceptives [23] . Hence, changes in the sympathetic nervous system, gender differences and changes in sex steroid concentrations may affect CGRP production and release.…”