Effects of hormone replacement therapy on the main fatty acids of serum and phospholipids of postmenopausal women.

Background: The anti-atherosclerotic effects of hormone replacement therapy (HRT) in postmenopausal women are partly mediated by improvement of the lipid and lipoprotein profiles. The present study aimed to investigate the effects of HRT on the main fatty acids of serum and phospholipids in postmenopausal women. Patients and Methods: Serum samples of two groups of postmenopausal women, receiving either single oestrogen or in combination with progestogens, were analysed before and after a 6- month treatment period. Results: Of the main serum fatty acids, there was a significant reduction in palmitic (p<0.05) and arachidonic acids (p<0.001), followed by an increase in oleic (p<0.05) and linoleic acids (p<0.05) in postmenopausal women receiving HRT compared to single oestrogen. The main fatty acids in phospholipids showed a similar pattern in those women. Conclusion: The above results demonstrate the beneficial effects of HRT in reducing the risk of cardiovascular disease through modification of the fatty acid profiles of postmenopausal women. During the menopause, significant reductions in the circulating levels of oestradiol and estrone are believed to influence hepatic lipid and lipoprotein metabolism (1). Postmenopausal women usually have increased levels of the atherogenic LDL-cholesterol and decreased anti- atherogenic HDL-cholesterol, putting them at higher risk of developing cardiovascular disease (2). Oral hormone replacement therapy (HRT) has been shown to reverse these changes, acting as a primary preventive treatment for more than 35% of menopausal women, independent of their geographic location (3-5). Progestogens are commonly used in combination with oestrogens since they reduce the risk of endometrial neoplasia which is associated with oestrogen replacement therapy in postmenopausal women (6). The mechanism of the oestrogen-induced anti- atherosclerotic effects remains unclear and is currently the subject of extensive investigation. It has been suggested that the benefits of oestrogen therapy may result from its effects on the concentrations of lipids (7), lipoproteins (8), hemostatic factors, glucose (9), nitric oxide, endothelin-1 (10), insulin, uric acid (11) and vascular endothelial growth factor (12). Alterations of the serum phospholipids levels, being important structural and functional components of cell membranes and mitochondria, have also been associated with cardiovascular disease. The ratio of HDL- phospholipids to HDL-cholesterol may have a predictive value in the assessment of cardiovascular risk (13). Phospholipids confer integrity to cell membranes and regulate the enzymatic activity of various metabolic processes, so that changes in their concentration can affect lipoprotein levels (14, 15). Furthermore, there is supporting evidence for the influence of hormonal factors on the fatty acid content and metabolism in women (16-18). Studies have shown that HRT reduces the proportion of polyunsaturated fatty acids in the platelet membranes of postmenopausal women (19) and that the fatty acid composition of tissues is believed to influence their responsiveness to insulin by modifying cell membrane properties (20). In order to elucidate the mechanism of action of HRT on lipid metabolism, with particular emphasis on the main fatty acids content, serum and phospholipid samples of two groups of postmenopausal women, receiving either single oestrogen or in combination with progestogens, were analysed before and after a treatment period of 6 months.