Journal of Endocrinological Investigation

, Volume 28, Issue 9, pp 623–631 | Cite as

Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women

  • C. M. Francucci
  • D. Pantaleo
  • N. Iori
  • A. Camilletti
  • F. Massi
  • M. Boscaro
Original Articles
First Online:
Accepted:

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 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    Wenger NK. Coronary hearth disease: an older woman’s major health risk. BMJ 1997, 315: 1085–990.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Stevenson JC, Crook D, Godsland IF. Influence of age and menopause on serum lipids and lipoproteins in healthy women. Atherosclerosis 1993, 98: 83–90.PubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 10.
    Kenneth JE. Human body composition: in vivo methods. Physiol Rev 2000, 80: 649–80.Google Scholar
  11. 11.
    Herrington DM, Howard TD. From Presumed Benefit to Potential Harm-Hormone Therapy and Heart Disease. N Engl J Med 2003, 349: 519–21.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Clemons M, Gross P. Estrogen and the risk of breast cancer. N Engl J Med 2001, 344: 276–85.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.Google Scholar
  19. 19.
    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.PubMedGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    American Heart Association. 2000 heart and stroke statistical update. Dallas, TX: American Heart Association. 1999, 1–29.Google Scholar
  24. 24.
    Barret-Connor E, Bush TL. Estrogen and coronary heart disease in women. JAMA 1991, 265: 1861–7.CrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.CrossRefGoogle Scholar
  27. 27.
    Dimitrova KR, DeGroot K, Myers AK, Kim YD. Estrogen and homocysteine. Cardiovasc Res 2002, 53: 577–88.PubMedCrossRefGoogle Scholar
  28. 28.
    Pasquali R, Casimirri F, Labate AM, et al. Body weight, fat distribution and the postmenopausal status. Int J Obes 1994, 18: 614–21.Google Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar
  31. 31.
    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.PubMedCrossRefGoogle Scholar
  32. 32.
    Rebuffe-Scrivè M, Enk L, Crona N, et al. Fat cell metabolism in different regions in women. J Clin Invest 1985, 75: 1973–6.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    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.PubMedCrossRefGoogle Scholar
  34. 34.
    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.PubMedCrossRefGoogle Scholar
  35. 35.
    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.PubMedCrossRefGoogle Scholar
  36. 36.
    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.PubMedCrossRefGoogle Scholar
  37. 37.
    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.PubMedCrossRefGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    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.CrossRefGoogle Scholar
  40. 40.
    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.PubMedCrossRefGoogle Scholar
  41. 41.
    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.PubMedCrossRefGoogle Scholar
  42. 42.
    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.PubMedCrossRefGoogle Scholar
  43. 43.
    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.PubMedCrossRefGoogle Scholar
  44. 44.
    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.PubMedCrossRefGoogle Scholar
  45. 45.
    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.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedCrossRefGoogle Scholar
  47. 47.
    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.PubMedCrossRefGoogle Scholar
  48. 48.
    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.PubMedCrossRefGoogle Scholar
  49. 49.
    Warnick GR. Measurement of cholesterol and other lipoprotein constituents in the clinical laboratory. Clin Chem Lab Med 2000, 48: 287–300.Google Scholar
  50. 50.
    Legato MJ. Dyslipidemia, gender and the role of high-density lipoprotein cholesterol: implications for therapy. Am J Cardiol 2000, 86: 15L–18L.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedCrossRefGoogle Scholar
  53. 53.
    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.Google Scholar
  54. 54.
    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.CrossRefGoogle Scholar
  55. 55.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2005

Authors and Affiliations

  • C. M. Francucci
    • 1
  • D. Pantaleo
    • 2
  • N. Iori
    • 2
  • A. Camilletti
    • 1
  • F. Massi
    • 1
  • M. Boscaro
    • 1
  1. 1.Division of Endocrinology, Department of Internal MedicineUniversity of AnconaItaly
  2. 2.Medical DepartmentEli Lilly Italia SpAFlorenceItaly

Personalised recommendations