Elsevier

Atherosclerosis

Volume 167, Issue 1, March 2003, Pages 121-127
Atherosclerosis

Effects of raloxifene on carotid blood flow resistance and endothelium-dependent vasodilation in postmenopausal women

https://doi.org/10.1016/S0021-9150(02)00420-3Get rights and content

Abstract

Raloxifene is one of the most important selective estrogen receptor modulators currently employed for the treatment of postmenopausal osteoporosis. However, it has also been suggested that this compound affects the vascular system. We evaluated both carotid blood flow resistance and endothelium-dependent vasodilation in 50 healthy postmenopausal women randomly assigned to receive, in a double blind design, either raloxifene (60 mg per day; N=25 subjects) or placebo (N=25 subjects) for 4 months. Indices of carotid blood flow resistance, such as the pulsatility index (PI) and resistance index (RI), as well as the flow-mediated brachial artery dilation were measured both at baseline and at the end of treatment. Changes in PI were −1.86±2.24 and −2.15±2.22% after placebo and raloxifene treatment, respectively, with no significant differences between groups. Changes in RI were −0.77±1.72 and −1.81±1.54% after placebo and raloxifene treatment, respectively, with no significant differences between groups. At the end of the treatment period, the increments in artery diameter measured after the flow stimulus were 10.79±2.39 and 6.70±1.23% for placebo and raloxifene, respectively, with no significant differences between groups. These results demonstrate no significant effects of raloxifene on either carotid blood flow resistance or brachial artery flow-mediated dilation in postmenopausal women.

Introduction

Observational studies demonstrate that the risk of cardiovascular events is reduced in postmenopausal women submitted to hormone replacement therapy [1], [2]. Estrogens are known to favorably influence several parameters of cardiovascular system, including lipid metabolism and endothelial function [3], [4]. However, at the same time, estrogens may have potentially negative effects on cardiovascular physiology and the recent Heart and Estrogen/Progestin Study Trial [5], raises questions about the beneficial effects of estrogens on the cardiovascular system so that alternatives to estrogens have been recently suggested for the prevention of postmenopausal osteoporosis in women affected by coronary heart disease [6].

Selective estrogen receptor modulators (SERMs) are compounds with mixed estrogen agonistic/antagonistic effects [7]. These properties, as well as the degree of selectivity, are different for the various SERMs with the consequence of potentially different effects of these molecules on human physiology [7]. In fact, the SERM tamoxifene has been shown to positively affect cardiovascular function in men affected by coronary heart disease [8], and postmenopausal administration of droloxifene [9] and raloxifene [10] have been shown to improve vascular reactivity. However, this particular issue of therapeutic strategies is still poorly addressed. For example, some of the studies published so far are not placebo-controlled and the selection criterion of the enrolled subjects varies among the different protocols. Furthermore, only a few data have been published on the effects of SERMs on carotid arteries and more investigations are needed to address this clinical topic.

In this study, we report data on the effects of raloxifene on both indices of carotid blood flow resistance and endothelium-dependent vasodilation in healthy postmenopausal women.

Section snippets

Methods

We studied 50 postmenopausal women with osteopenia. Postmenopausal status was defined as cessation of menses for at least 1 year or self-report of hysterectomy/oophorectomy and was confirmed (serum levels of follicle-stimulating hormone greater than 40 mU/ml and estradiol less than 60 pmol/l) before the enrolment. Osteopenia was demonstrated by bone density measurement and was defined as a percentage decrease in bone mass between −1 and −2.5 standard deviations with respect to values observed

Results

No significant differences were found between the two groups in either age (58.81±0.8 years vs. 57.55±0.9 years in placebo vs. raloxifene, respectively; P=0.39) or in time since menopause (7.8±1.0 vs. 8.5±0.7 in placebo vs. raloxifene, respectively; P=0.61; Table 1). No significant changes between groups were found in either pulse rate or systolic and diastolic blood pressure either at the beginning or at the end of the study (data not shown). The compliance with treatment was good for each

Discussion

These results demonstrate the lack of effect of raloxifene on both carotid blood flow resistance and brachial artery flow-mediated dilation. Carotid blood flow resistance has been shown to be increased in the postmenopausal status [13] and to be reduced by postmenopausal estrogen treatment [20], [21], although contrasting data have been reported [18], [22]. The question on whether SERMs are able to affect carotid blood flow is poorly addressed, at present. Although studies have demonstrated

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