National differences in lipid response to postmenopausal hormone replacement therapy
Introduction
Large national differences in serum lipids and cardiovascular mortality [1] may be explained by interaction of genetic [2], [3] and dietary and lifestyle factors [4], [5]. Postmenopausal hormone replacement therapy (HRT) causes a number of beneficial changes in blood lipids, such as reduction in total cholesterol, LDL-cholesterol (LDL), and lipoprotein(a) (Lp(a)), as well as a rise in HDL-cholesterol (HDL) [4], [6]. These changes, which may contribute to the efficacy of HRT in primary prevention of cardiovascular diseases, as suggested by observational studies [7], [8], [9], are to some extent dependent on the routes of administration of HRT [10], [11]. As regards secondary prevention of ischemic heart disease by HRT, the data are far from being uniform [12], [13], [14], [15], [16], [17]. It is unknown, however, whether changes in lipid metabolism during HRT show ethnic and, thus, national differences. We investigated this question in the context of a large multinational study on the acceptability of continuous transdermal estradiol replacement therapy combined with transdermal or oral progestin in postmenopausal women [18].
Section snippets
Subjects
With the approval of local ethics committees, a total of 774 healthy, postmenopausal, nonhysterectomized women were included in the trial [18]. All received written information on the purpose and conduct of the study and gave their written consent. Pre- and on-treatment data were available from 567 women from five European countries (Belgium and Sweden, each five centers; Finland, six centers; the Netherlands and the UK, each eight centers) (Table 1). All women received 50 μg/day of
Results
Baseline lipid and lipoprotein levels showed no statistically significant differences between the five countries (Table 3). Changes in total cholesterol, HDL, HDL2, and triglycerides were correlated with pre-treatment BMI, and changes in triglycerides also with systolic blood pressure (Table 4), but these effects were similar in each country. Total cholesterol was reduced by 3–5% in every country (Table 3). The range of response of total HDL cholesterol was from −1% in the UK to +5% in Belgium.
Discussion
We examined the hypothesis of national differences in the response of lipids and lipoproteins to HRT in the context of a large study in five European countries on the effects of 50 mg/day transdermal estradiol with six schedules of progestogen addition [18]. Majority of the women received transdermal NETA. Estrogen component is the most significant determinant for lipid changes during HRT [19]. In this regard the regimens used in our study were comparable. A progestin component bears an
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