Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women
First Online: 28 March 2014 Accepted: 16 February 2005 DOI:
Cite this article as: Francucci, C.M., Pantaleo, D., Iori, N. et al. J Endocrinol Invest (2005) 28: 623. doi:10.1007/BF03347261 Abstract
The aim of our prospective, randomised, controlled and open-label clinical study was to evaluate in healthy post-menopausal women the effects of raloxifene (RLX) on body fat distribution and lipids, and the correlations between these parameters. The fat distribution, by dual energy X-ray absorptiometry, and lipids were evaluated at baseline and after 1 yr in 50 postmenopausal women: 25 were treated with RLX 60 mg/die, while 25 served as control group (CG). After 1 yr, we observed in RLX-users a slight reduction of fat mass in trunk and central region and an increase in legs and, in relation to CG, significantly lower values of adiposity in trunk and abdominal region (
p<0.05). At the same time, HDL-cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly increased in relation to baseline values and CG ( p<0.05) and apolipoprotein B (ApoB), total cholesterol/HDL-C, LDL cholesterol/HDL-C, and ApoB/ApoA1 ratios significantly decreased compared to baseline values and CG ( p<0.05). No correlation was underlined among lipids and regional fat distribution. These results highlight the positive effect of RLX on lipids and suggest, for the first time, that RLX promotes the shift from android to gynoid fat distribution, and prevents the uptrend of abdominal adiposity and body weight compared with untreated women. Key-words Raloxifene fat distribution lipids
An erratum to this article is available at
. http://dx.doi.org/10.1007/BF03347585 References
Cummings SR, Black DM, Rubin SM. Lifetime risks of hip, colles or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 1989, 149: 2445–8.
Wenger NK. Coronary hearth disease: an older woman’s major health risk. BMJ 1997, 315: 1085–990.
PubMedCentral PubMed CrossRef
Melton LJ, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral density assessed at different skeletal sites. J Bone Miner Res, 1993, 8: 1227–34.
Matthews KA, Meilanhn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med 1989, 321: 641–6.
Stevenson JC, Crook D, Godsland IF. Influence of age and menopause on serum lipids and lipoproteins in healthy women. Atherosclerosis 1993, 98: 83–90.
Poehlman ET, Toth MJ, Gardner AW. Changes in energy balance and body composition at menopause: a controlled longitudinal study. Ann Intern Med 1995, 123: 673–5.
Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey. 1988–1994. Arch Intern Med 2003, 163: 427–36.
PubMedCentral PubMed CrossRef
Bonora E, Del Prato S, Bonadonna RC, et al. Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women. Diabetes 1992, 41: 1151–9.
Bertrais S, Balkau B, Vol S, et al. Relationship between abdominal body fat distribution and cardiovascular risk factors: an explanation for women’s healthier cardiovascular risk profile. The D.E.S.I.R. Study. Int J Obes 1999, 23: 1085–94.
Kenneth JE. Human body composition: in vivo methods. Physiol Rev 2000, 80: 649–80.
Herrington DM, Howard TD. From Presumed Benefit to Potential Harm-Hormone Therapy and Heart Disease. N Engl J Med 2003, 349: 519–21.
Gambacciani M, Ciaponi M, Cappagli B, et al. Body weight, body distribution and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab 1997, 82: 414–7.
Samaras K, Hayward CS, Sullivan D, Kelly RP, Campbell LV. Postmenopausal replacement therapy on central abdominal fat, glycemic control, lipid metabolism and vascular factors in type 2 diabetes. Diabetes Care 1999, 22: 1401–7.
Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995, 85: 304–13.
Clemons M, Gross P. Estrogen and the risk of breast cancer. N Engl J Med 2001, 344: 276–85.
Kauffman RF, Bensch WR, Roudebush RE, et al. Hypocholesterolemic activity of raloxifene (LY139481): pharmacological characterization as a selective estrogen receptor modulator. J Pharmacol Exp Ther 1997, 280: 146–53.
Bjarnason NH, Haarbo J, Byrjalsen I, Alexandersen P, Kauffman RF, Christiansen C. Raloxifene and estrogen reduces progression of advanced atherosclerosis—a study in ovariectomized, cholesterol-fed rabbits. Atherosclerosis 2001, 154: 97–102.
O’Neill TW, Cooper C, Algra D, Pols HAP, Agnusdei D, Dequeker J. On behalf of the European Vertebral Osteoporosis Study Group Design and development of a questionnaire for use in a multicentre study of vertebral osteoporosis in Europe: The European Vertebral Osteoporosis Study (EVOS). Rheumatol Eur 1995, 24/2: 75–81.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972, 18: 499–502.
Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. Abdominal fat and insulin resistance in normal and overweight women. Diabetes 1996, 45: 633–8.
Ross R, Shaw K, Martel Y, De Wise J, Avruch L. Adipose tissue distribution measured by magnetic resonance imaging in obese women. Am J Clin Nutr 1993, 57: 470–5.
Jensen MD, Kanaley JA, Reed JE, Sheedy PF. Measurement of abdominal and visceral fat with computed tomography and dual energy X-ray absorptiometry. Am J Clin Nutr 1995, 61: 274–8.
American Heart Association. 2000 heart and stroke statistical update. Dallas, TX: American Heart Association. 1999, 1–29.
Barret-Connor E, Bush TL. Estrogen and coronary heart disease in women. JAMA 1991, 265: 1861–7.
De Aloysio D, Gambacciani M, Meschia M, et al. The Icarus Study Group. The effect of menopause on blood lipids and lipoprotein levels. Atherosclerosis 1999, 147: 147–53.
Saitta A, Altavilla D, Cucinotta D, et al. Randomized, doubleblind, placebo controlled study on the effects of raloxifene and hormone replacement therapy on plasma nitric oxide concentrations, endothelin-1 levels and endothelium-de-pendent vasodilation in postmenopausal women. Arterio-scler Thromb Vasc Biol 2001, 21: 1512–9.
Dimitrova KR, DeGroot K, Myers AK, Kim YD. Estrogen and homocysteine. Cardiovasc Res 2002, 53: 577–88.
Pasquali R, Casimirri F, Labate AM, et al. Body weight, fat distribution and the postmenopausal status. Int J Obes 1994, 18: 614–21.
Toth MJ, Tchernof A, Sites CK, Poehlman ET. Effect of menopausal status on body composition and abdominal fat distribution. Int J Obes Relat Metab Disord 2000, 24: 226–31.
Douchi T, Yamamoto S, Yoshimitsu N, Andoh T, Matsuo T, Nagata Y. Relative contribution of aging and menopause to changes in lean and fat mass in segmental regions. Maturitas 2002, 42: 301–6.
Paradisi G, Smith L, Burtner C, et al. Dual Energy X-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome. Diabetes Care 1999, 22: 1310–7.
Rebuffe-Scrivè M, Enk L, Crona N, et al. Fat cell metabolism in different regions in women. J Clin Invest 1985, 75: 1973–6.
PubMedCentral PubMed CrossRef
Rebuffe-Scrivè M, Eldh J, Hafstrom L, Bjorntorp P. Metabolism of mammary, abdominal and femoral adipocytes in women before and after menopause. Metabolism 1986, 35: 792–7.
Brunzell JD, Hokanson JE. Dyslipidemia of central obesity and insulin resistance. In Proceedings of the Conference on Therapeutic Approaches to Type 2 Diabetes. Diabetes Care 1999, 22: C10–3.
Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997, 337: 1641–7.
Walsh BW, Kuller LH, Wild RA, et al. Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women. JAMA 1998, 279: 1445–51.
Lufkin EG, Whitaker MD, Nickelsen T, et al. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res. 1998, 13: 1747–54.
Meunier PJ, Vignot E, Garnero P, et al. Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group. Osteoporos Int 1999, 10: 330–6.
Conrad Johnson C, Bjarnason NH, Cohen FJ, et al. Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women. Arch Int Med 2000, 160: 3444–50.
Nickelsen T, Creatsas G, Rechberger T, et al. Euralox 1 Study Group. Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study. Climacteric 2001, 4: 320–31.
Tsai KS, Yen ML, Pan HA, et al. Raloxifene versus continuous combined estrogen/progestin therapy: densitometric and biochemical effects in healthy postmenopausal Taiwanese women. Osteoporos Int 2001, 12: 1020–5.
De Leo V, La Marca A, Morgante G, Lanzetta D, Setacci C, Petraglia F. Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women. Am J Obstet Gynecol 2001, 184: 350–3.
Anderson PW, Cox DA, Sashegyi A, Paul S, Silfen SL, Walsh BW. Effects of raloxifene and hormone replacement therapy on markers of serum atherogenicity in healthy postmenopausal women. Maturitas 2001, 39: 71–7.
Barrett-Connor E, Grady D, Sashegyi A, et al. MORE Investigators (Multiple Outcomes of Raloxifene Evaluation). Raloxifene and cardiovascular events in osteoporotic postmenopausal women. JAMA 2002, 287: 847–57.
Bloch-Thomsen A, Silvestri S, Christiansen C, Bjarnason NH. Associated response in bone mineral density and atherogenic lipid profile during treatment with two different selective estrogen receptor modulators: levormeloxifene and raloxifene. Climacteric 2003, 6: 159–67.
Kung AW, Chao HT, Huang KE, et al. Efficacy and safety of raloxifene 60 milligrams/day in postmenopausal Asian women. J Clin Endocrinol Metab 2003, 88: 3130–6.
Barrett-Connor E, Ensrud KE, Harper K, et al. Post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes. Clin Ther 2003, 25: 919–30.
Cagnacci A, Paoletti AM, Zanni A, et al. Raloxifene does not modify insulin sensitivity and glucose metabolism in postmenopausal women. J Clin Endocrinol Metab 2002, 87: 4117–21.
Warnick GR. Measurement of cholesterol and other lipoprotein constituents in the clinical laboratory. Clin Chem Lab Med 2000, 48: 287–300.
Legato MJ. Dyslipidemia, gender and the role of high-density lipoprotein cholesterol: implications for therapy. Am J Cardiol 2000, 86: 15L–18L.
Lemieux I., Lamarche B, Couillard C, et al. Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med 2001, 161: 2685–92.
Walldius G, Jungner I, Holme I, Aastveit AH, Kolar W, Steiner E. High apolipoprotein-B, low apolipoproteinA-1, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet 2001, 358: 2026–33.
Cucinelli F, Soranna L, Romualdi D, Muzj G, Mancuso S, Lanzone A. The effect of raloxifene on glyco-insulinemic homeostasis in healthy postmenopausal women: a randomized placebo-controlled study. Clin Chem Lab Med 2002, 87: 122–8.
Andersson B, Johannsson G, Holm G, et al. Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial. J Clin Endocrinol Metab 2002, 87, 4186–92.
Lee CC, Kasa-Vubu JZ, Supiano MA. Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women. J Am Geriatr Soc. 2003, 51: 683–8.
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