Skip to main content
SpringerLink
Log in

Raloxifene

  • Adis New Drug Profile
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

  • ▴ Raloxifene is a selective estrogen receptor modulator which mimics the effects of estrogens on bone and blood lipid levels without stimulatory effects on the breast or uterus.

  • ▴ Raloxifene inhibits estrogen-dependent proliferation of human breast cancer cells in vitro and development of induced mammary tumours in rats in vivo.

  • ▴ Raloxifene inhibits bone resorption induced by estrogen deficiency in murine and human studies and lowers serum cholesterol levels. In clinical studies in postmenopausal women, raloxifene 60 mg/day for 2 years significantly increased bone mineral density compared with placebo.

  • ▴ In comparative clinical studies, raloxifene 60 mg/day had more modest effects than conjugated estrogens 0.625 mg/day on bone resorption and formation parameters and appeared to be less effective in increasing bone mineral density.

  • ▴ In older postmenopausal women with existing bone fractures, raloxifene 60 or 120 mg/day for 1 year produced modest increases in bone mineral density.

  • ▴ The most common treatment-related adverse events in raloxifene recipients were hot flushes and leg cramps. The risk of venous thromboembolic events is increased during raloxifene therapy. In contrast with conjugated estrogens 0.625 mg/day, raloxifene 200 or 600 mg/day for 8 weeks or 150 mg/day for 1 year did not produce endometrial proliferation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 57705 women with breast cancer and 108411 women without breast cancer. Lancet 1997; 350: 1047–59

    Article  Google Scholar 

  2. Compston JE. Prevention and management of osteoporosis: current trends and future prospects. Drugs 1997 May; 53: 727–35

    Article  PubMed  CAS  Google Scholar 

  3. Patel S. Current and potential future drug treatments for osteoporosis. Ann Rheum Dis 1996 Oct; 55: 700–14

    Article  PubMed  CAS  Google Scholar 

  4. Hol T, Cox MB, Bryant HU, et al. Selective estrogen receptor modulators and postmenopausal women’s health. J Womens Health 1997; 6: 523–31

    Article  PubMed  CAS  Google Scholar 

  5. Black LJ, Jones CD, Falcone JF. Antagonism of estrogen action with a new benzothiophene derived antiestrogen. Life Sci 1983 Feb 28; 32: 1031–6

    Article  PubMed  CAS  Google Scholar 

  6. Glasebrook AL, Phillips DL, Sluka JP. Multiple binding sites for the anti-estrogen raloxifene. J Bone Miner Res 1993; 8Suppl. 1: S268

    Google Scholar 

  7. Yang NN, Bryant HU, Hardikar S, et al. Estrogen and raloxifene stimulate transforming growth factor-beta 3 gene expression in rat bone: a potential mechanism for estrogen- or raloxifenemediated bone maintenance. Endocrinology 1996 May; 137: 2075–84

    Article  PubMed  CAS  Google Scholar 

  8. Yang NN, Venugopalan M, Hardikar S, et al. Identification of an estrogen response element activated by metabolites of 17-beta-estradiol and raloxifene. Science 1996 Aug 30; 273: 1222–5

    Article  PubMed  CAS  Google Scholar 

  9. Fournier B, Häring S, Kaye AM, et al. Stimulation of creatine kinase specific activity in human osteoblast and endometrial cells by estrogens and anti-estrogens and its modulation by calciotropic hormones. J Endocrinol 1996 Aug; 150: 275–85

    Article  PubMed  CAS  Google Scholar 

  10. Black LJ, Sato M, Rowley ER, et al. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest 1994 Jan; 93: 63–9

    Article  PubMed  CAS  Google Scholar 

  11. Turner CH, Sato M, Bryant HU. Raloxifene preserves bone strength and bone mass in ovariectomized rats. Endocrinology 1994 Nov; 135: 2001–5

    Article  PubMed  CAS  Google Scholar 

  12. Sato M, Bryant HU, Iversen P, et al. Advantages of raloxifene over alendronate or estrogen on nonreproductive and reproductive tissues in the long-term dosing of ovariectomized rats. J Pharmacol Exp Ther 1996 Oct; 279: 298–305

    PubMed  CAS  Google Scholar 

  13. Bryant HU, Cole HW, Rowley ER, et al. Raloxifene and LY117018 prevent bone loss induced by an LH-RH agonist, without estrogen-like stimulation of the uterus [abstract]. 10th ICE: 1996 Jun 12; I: 572

    Google Scholar 

  14. Evans GL, Bryant HU, Magee DE, et al. Raloxifene inhibits bone turnover and prevents further cancellous bone loss in adult ovariectomized rats with established osteopenia. Endocrinology 1996 Oct; 137: 4139–44

    Article  PubMed  CAS  Google Scholar 

  15. Sato M, Kim J, Bryant H. Raloxifene effects in vivo and on rat osteoclasts [abstract]. Bone 1995 Jan; 16 Suppl.: 184

    Google Scholar 

  16. Heaney RP, Draper MW. Raloxifene and estrogen: comparative bone-remodeling kinetics. J Clin Endocrinol Metab 1997; 82: 3425–9

    Article  PubMed  CAS  Google Scholar 

  17. Delmas PD, Bjarnason NH, Mitlak B, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337(23): 1641–7

    Article  PubMed  CAS  Google Scholar 

  18. Lufkin EG, Whitaker MD, Argueta R, et al. Raloxifene treatment of postmenopausal osteoporosis. J Bone Miner Res 1997; 12: S150

    Google Scholar 

  19. Gunness M, Prestwood K, Lu Y, et al. Histomorphometric, bone marker, and bone mineral density response to raloxifene HCl and Premarin in postmenopausal women [abstract no. OR4-2]. Program. The Endocrine Society 79th Annual Meeting: 1997 Jun 11–14: Minneapolis. Bethesda (MD): The Endocrine Society Press, 1997: 67

    Google Scholar 

  20. Draper MW, Flowers DE, Huster WJ, et al. A controlled trial of raloxifene (LY139481) HCl: impact on bone turnover and serum lipid profile in healthy postmenopausal women. J Bone Miner Res 1996 Jun; 11: 835–42

    Article  PubMed  CAS  Google Scholar 

  21. Bjarnason NH, Haarbo J, Byrjalsen I, et al. Raloxifene inhibits aortic accumulation of cholesterol in ovariectomized, cholesterol-fed rabbits. Circulation 1997; 96: 1964–9

    Article  PubMed  CAS  Google Scholar 

  22. 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 Jan; 280: 146–53

    PubMed  CAS  Google Scholar 

  23. Walsh BW, Kuller LH, Wild RA, et al. The effect of raloxifene on markers of cardiovascular risk in healthy, postmenopausal women. Atherosclerosis 1997; 134(1,2): 182

    Article  Google Scholar 

  24. Wakeling AE, Valcaccia B, Newboult E, et al. Non-steroidal antioestrogens—receptor binding and biological response in rat uterus, rat mammary carcinoma and human breast cancer cells. J Steroid Biochem 1984 Jan; 20: 111–20

    Article  PubMed  CAS  Google Scholar 

  25. Labrie F, Poulin R, Simard J, et al. Interactions between estrogens, androgens, progestins, and glucocorticoids in ZR-75-1 human breast cancer cells. Ann N Y Acad Sci 1990; 595: 130–48

    Article  PubMed  CAS  Google Scholar 

  26. Wiznitzer I, Benz C. Tamoxifen versus LY156758 for treatment of human breast and prostate cancer in vitro. Breast Cancer Res Treat 1983; 3: 305

    Google Scholar 

  27. Clemens JA, Bennett DR, Black LJ, et al. Effects of a new antiestrogen, keoxifene (LY156758), on growth of carcinogen-induced mammary tumors and on LH and prolactin levels. Life Sci 1983 Jun 20; 32: 2869–75

    Article  PubMed  CAS  Google Scholar 

  28. Anzano MA, Peer CW, Smith JM, et al. Chemoprevention of mammary carcinogenesis in the rat: combined use of raloxifene and 9-cis-retinoic acid. J Natl Cancer Inst 1996 Jan 17; 88: 123–5

    Article  PubMed  CAS  Google Scholar 

  29. Gottardis MM, Jordan VC. Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 1987 Aug 1; 47: 4020–4

    PubMed  CAS  Google Scholar 

  30. Labrie F, Veilleux R, Fournier A. Glucocorticoids stimulate the growth of mouse mammary carcinoma Shionigi cells in culture. Mol Cell Endocrinol 1988; 58(2–3): 207–11

    Article  PubMed  CAS  Google Scholar 

  31. Swisher DK, Tague RM, Seyler DE. Effect of the selective estrogen receptor modulator raloxifen on explanted uterine growth in rats. Drug Dev Res 1995 Sep; 36: 43–5

    Article  Google Scholar 

  32. Fuchs-Young R, Rippy MK, Dorr FA, et al. Raloxifene diminishes the uterotrophic effects of tamoxifen in treated ovariectomized rats [abstract]. Breast Cancer Res Treat 1994; 32 Suppl.: 78

    Google Scholar 

  33. Huster W, Shah A, Cohen F, et al. Effect of raloxifene on the endometrium in healthy postmenopausal women. The North American Menopause Society 8th Annual Meeting: 1997 Sept 4–6; Boston, Massachusetts

  34. Boss SM, Huster WJ, Neild JA, et al. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol 1997; 177: 1458–64

    Article  PubMed  CAS  Google Scholar 

  35. Scheele W, Symanowski SM, Neale S, et al. Raloxifene does not cause stimulatory effects on the uterus in healthy postmenopausal women [abstract no. P#-246]. Program. The Endocrine Society 79th Annual Meeting: 1997 Jun 11–14: Minneapolis. Bethesda (MD): The Endocrine Society Press, 1997: 498

    Google Scholar 

  36. Ortmann O, Emons G, Knuppen R, et al. Inhibitory actions of keoxifene on luteinizing hormone secretion in pituitary gonadotrophs. Endocrinology 1988 Aug; 123: 962–8

    Article  PubMed  CAS  Google Scholar 

  37. Simard J, Labrie F. Keoxifene shows pure antiestrogenic activity in pituitary gonadotrophs. Mol Cell Endocrinol 1985 Feb; 39: 141–4

    Article  PubMed  CAS  Google Scholar 

  38. Petersen SL, Cheuk C, Hartman RD, et al. Medial preoptic microimplants of the antiestrogen, keoxifene, affect luteinizing hormone-releasing hormone messenger RNA levels, median eminence luteinizing hormone- releasing hormone concentrations and luteinizing ho rmone release in ovariectomized, estrogen-treated rats. J Neuroendocrinol 1989; 1: 279–83

    Article  PubMed  CAS  Google Scholar 

  39. Draper MW, Flowers DE, Neild JA, et al. Antiestrogenic properties of raloxifene. Pharmacology 1995 Apr; 50: 209–17

    Article  PubMed  CAS  Google Scholar 

  40. Knadler MP, Lantz RJ, Gillespie TA, et al. The disposition and metabolism of 14C-labeled raloxifene in humans [abstract]. Pharm Res 1995 Sep; 12 Suppl.: 372

    Google Scholar 

  41. Allerheiligen S, Geiser J, Knadler M, et al. Raloxifene pharmacokinetics and the associated endocrine effects in premenopausal women treated during the follicular, ovulatory, and luteal phases of the menstrual cycle [abstract]. Pharm Res 1996 Sep; 13 Suppl.: 430

    Google Scholar 

  42. Ni L, Allerheiligen SRB, Basson R, et al. Pharmacokinetics of raloxifene in men and postmenopausal women volunteers [abstract]. Pharm Res 1996 Sep; 13 Suppl.: 430

    Google Scholar 

  43. Eli Lilly and Company. Raloxifene prescribing information. Indianapolis, USA

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Julia A. Balfour & Karen L. Goa

Authors
  1. Julia A. Balfour
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen L. Goa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julia A. Balfour.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balfour, J.A., Goa, K.L. Raloxifene. Drugs Aging 12, 335–341 (1998). https://doi.org/10.2165/00002512-199812040-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199812040-00006

Keywords

Search

Navigation