Selective Estrogen Receptor Modulators (SERMs): State of the Art

  • Santiago PalaciosEmail author


The function of selective estrogen receptor modulators (SERMs) is to produce specific positive effects on certain target tissues with estrogen receptors and negative or neutral effects on other tissues with estrogen receptors but in which no action is required.

Relevant articles in English are published between 1980 and 2018, which have been identified through the PubMed database (search string “selective estrogen receptor modulator or SERM”).

Tamoxifen is a drug used in the treatment of hormone-dependent breast cancer and in primary prevention in women at high risk of developing the disease. Raloxifene is the first SERM approved to prevent and treat osteoporosis. Raloxifene is also as effective as tamoxifen in reducing the risk of breast cancer in postmenopausal women. Bazedoxifene has been shown to be effective in reducing vertebral and, in a high-risk group, non-vertebral fractures. Ospemifene is the first SERM for the treatment of dyspareunia in the USA and for patients with vulvovaginal atrophy who are not eligible for estrogen therapy in Europe.

SERMs have a specific action different from that of estrogens. They all have a unique tissue-specific effect that make them different from each other and therefore have different applications.


Selective estrogen receptor modulator Tissue-specific effect Tamoxifen Raloxifene Bazedoxifene Ospemifene 


  1. 1.
    Palacios S, Coronado PJ. New options for menopausal symptoms after 15 years of WHI Study. Minerva Ginecol. 2017;69(2):160–70.PubMedPubMedCentralGoogle Scholar
  2. 2.
    The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728–53.CrossRefGoogle Scholar
  3. 3.
    Palacios S, Henderson VW, Siseles N, Tan D, Villaseca P. Age of menopause and impact of climacteric symptoms by geographical region. Climacteric. 2010;13(5):419–28.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Palacios S, Nappi RE, Bruyniks N, Particco M, Panay N, EVES Study Investigators. The European Vulvovaginal Epidemiological Survey (EVES): prevalence, symptoms and impact of vulvovaginal atrophy of menopause. Climacteric. 2018;21(3):286–91.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Boschitsch EP, Durchschlag E, Dimai HP. Age-related prevalence of osteoporosis and fragility fractures: real-world data from an Austrian Menopause and Osteoporosis Clinic. Climacteric. 2017;20(2):157–63.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Baber RJ, Panay N, Fenton A, IMS Writing Group. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109–50.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Cobin RH, Goodman NF, AACE Reproductive Endocrinology Scientific Committee. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on Menopause-2017 update. Endocr Pract. 2017;23(7):869–80.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Woods NF, Utian W. Quality of life, menopause, and hormone therapy: an update and recommendations for future research. Menopause. 2018;25(7):713–20.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2010;17:194–203.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    NICE. Medicines adherence clinical guideline CG76. Report no.: CG76; 2009.Google Scholar
  11. 11.
    Newton KM, Reed SD, Nekhyludov L, Grothaus LC, Ludman EJ, Ehrlich K, et al. Factors associated with successful discontinuation of hormone therapy. J Womens Health (Larchmt). 2014;23(5):382–8.CrossRefGoogle Scholar
  12. 12.
    Palacios S, Brincat M, Erel CT, Gambacciani M, Lambrinoudaki I, Moen MH, et al. EMAS clinical guide: selective estrogen receptor modulators for postmenopausal osteoporosis. Maturitas. 2012;71(2):194–8.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan V, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med. 1992;326(13):852–6.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 1999;282(7):637–45. Erratum in: JAMA 1999 Dec 8;282(22):2124.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al.; National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006;295(23):2727–41.Google Scholar
  16. 16.
    Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al.; Raloxifene Use for The Heart (RUTH) Trial Investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355(2):125–37.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Peng L, Luo Q, Lu H. Efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(49):e8659.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Senshio, INN-ospemifene—European Medicines Agency.
  19. 19.
    Meegan MJ, Lloyd DG. Advances in the science of estrogen receptor modulation. Curr Med Chem. 2003;10(3):181–210.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Palacios S. The future of the new selective estrogen receptor modulators. Menopause Int. 2007;13(1):27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Palacios S. Third generation SERMs: anything new? Maturitas. 2010;67(2):101–2.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. 2013;8(2):135–55.Google Scholar
  23. 23.
    Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997;389(6652):753–8.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Tzukerman MT, Esty A, Santiso-Mere D, Danielian P, Parker MG, Stein RB, et al. Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol. 1994;8(1):21–30.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Jordan VC, Morrow M. Tamoxifen, raloxifene, and the prevention of breast cancer. Endocr Rev. 1999;20(3):253–78.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Wickerham L. Tamoxifen—an update on current data and where it can now be used. Breast Cancer Res Treat. 2002;75(Suppl 1):S7–12; discussion S33–5.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Nolvadex Adjuvant Trial Organisation. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer. Interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet. 1983;1(8319):257–61.Google Scholar
  29. 29.
    Cuzick J, Baum M. Tamoxifen and contralateral breast cancer. Lancet. 1985;2(8449):282.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Rose PG. Endometrial carcinoma. N Engl J Med. 1996;335:640–9.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrère CH, Otter R, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994;343:448–52.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Davis SR, Robinson PJ, Jane F, White S, Brown KA, Piessens S, et al. The benefits of adding metformin to tamoxifen to protect the endometrium—a randomized placebo-controlled trial. Clin Endocrinol (Oxf). 2018;89(5):605–12.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451–67.CrossRefGoogle Scholar
  34. 34.
    Ding H, Field TS. Bone health in postmenopausal women with early breast cancer: how protective is tamoxifen? Cancer Treat Rev. 2007;33(6):506–13.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Rabaglio M, Sun Z, Price KN, Castiglione-Gertsch M, Hawle H, Thürlimann B, et al.; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol. 2009;20(9):1489–98.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kyvernitakis I, Kostev K, Hadji P. The tamoxifen paradox-influence of adjuvant tamoxifen on fracture risk in pre- and postmenopausal women with breast cancer. Osteoporos Int. 2018;29(11):2557–64.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Sinawat S, Buppasiri P, Lumbiganon P, Pattanittum P. Long versus short course treatment with metformin and clomiphene citrate for ovulation induction in women with PCOS. Cochrane Database Syst Rev. 2012;(10):CD006226.Google Scholar
  38. 38.
    Uyar Y, Koltan SO, Pögün S, Vatansever S, Caglar H. The effect of clomiphene citrate on osteoporosis in ovariectomized rats. Arch Gynecol Obstet. 2008;278(2):107–14.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Yilmaz S, Yilmaz Sezer N, Gönenç İM, İlhan SE, Yilmaz E. Safety of clomiphene citrate: a literature review. Cytotechnology. 2018;70(2):489–95.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Qu Q, Zheng H, Dahllund J, Laine A, Cockcroft N, Peng Z, et al. Selective estrogen effects of a novel triphenylethylene compound, FC1271 a, on bone, cholesterol level, and reproductive tissues in intact ovariectomized rats. Endocrinology. 2000;141:809–20.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Taras TL, Wurz GT, DeGregorio MW. In vitro and in vivo effects of ospemifene (FC-1271a) in breast cancer. J Steroid Biochem Mol Biol. 2001;77:271–9.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Wurz GT, Read KC, Marchisano-Karpman C, Gregg JP, Beckett LA, Yu Q, et al. Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice. J Steroid Biochem Mol Biol. 2005;97(3):230–40.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Komi J, Lankinen KS, Harkonen P, DeGregorio MW, Voipio S, Kivinen S, et al. Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women. Menopause. 2005;12(2):202–9.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Bachmann GA, Komi JO. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause. 2010;17:480–6.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Simon J, Lin V, Radovich C, Bachmann GA, The Ospemifene Study Group. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause. 2013;20:418–27.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Portman DJ, Bachmann G, Simon J, The Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623–30.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Simon JA, Altomare C, Cort S, Jiang W, Pinkerton JV. Overall safety of ospemifene in postmenopausal women from placebo-controlled phase 2 and 3 trials. J Womens Health (Larchmt). 2018;27(1):14–23.CrossRefGoogle Scholar
  48. 48.
    Vogel CL, Johnston MA, Capers C, Braccia D. Toremifene for breast cancer: a review of 20 years of data. Clin Breast Cancer. 2014;14(1):1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Mustonen MV, Pyrhönen S, Kellokumpu-Lehtinen PL. Toremifene in the treatment of breast cancer. World J Clin Oncol. 2014;5(3):393–405.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Mao C, Yang ZY, He BF, Liu S, Zhou JH, Luo RC, et al. Toremifene versus tamoxifen for advanced breast cancer. Cochrane Database Syst Rev. 2012;(7):CD008926.Google Scholar
  51. 51.
    Erkkola R, Mattila L, Powles T, Heikkinen J, Toivola B, Korhonen P, et al. Bone mineral density and lipid changes during 5 years of follow-up in a study of prevention of breast cancer with toremifene in healthy, high-risk pre- and post-menopausal women. Breast Cancer Res Treat. 2005;93(3):277–87.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Pickar JH, MacNeil T, Ohleth K. SERMs: progress and future perspectives. Maturitas. 2010;67(2):129–38.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Wolmark N. The study of tamoxifen and raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial. Clin Breast Cancer. 2002;3:153–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Black LJ, Sato M, Rowley ER, Magee DE, Bekele A, Williams DC, et al. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J Clin Invest. 1994;93(1):63–9.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S. Time dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HC1, tamoxifen, estrogen and alendronate. Bone. 1996;18:621–7.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Anzano MA, Peer CW, Smith JM, Mullen LT, Shrader MW, Logsdon DL, et al. Chemoprevention of mammary carcinogenesis in the rat: combined use of raloxifene and 9-cis-retinoic acid. J Natl Cancer Inst. 1996;88:23–5.CrossRefGoogle Scholar
  57. 57.
    Seeman E, Crans GG, Diez-Perez A, Pinette KV, Delmas PD. Anti-vertebral fracture efficacy of raloxifene: a meta-analysis. Osteoporos Int. 2006;17(2):313–6.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Cancer Res Treat. 2001;65:125–34.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Martino S, Cauley JA, Barrett-Connor E, Powles TJ, Mention J, Disch D, et al. Continuing outcomes relevant to evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004;96:1751–61.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Cohen FJ, Watts S, Shah A, Akers R, Plouffe L Jr. Uterine effects of 3-year raloxifene therapy in postmenopausal women younger than age 60. Obstet Gynecol. 2000;95:104–10.PubMedPubMedCentralGoogle Scholar
  61. 61.
    Goldstein SR, Neven P, Zhou L, iaylot YL, Ciaccia AV, Plouffle L. Raloxifene effect on frequency of surgery for pelvic floor relaxation. Obstet Gynecol. 2001;98:91–6.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Zhu XM, Zheng W, Li XH, Cai DB, Yang XH, Ungvari GS, et al. Adjunctive raloxifene for postmenopausal women with schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials. Schizophr Res. 2018. pii: S0920-9964(18)30037-9. Scholar
  63. 63.
    Sato M, Zeng GQ, Rowley E, Turner CH. LY353381 x HC1: an improved benzothiophe analog with bone efficacy complementary to parathyroid hormone-(1-34). Endocrinology. 1998;139:4642–51.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ. Comparative study of human and rat mammary tumorigenesis. Lab Investig. 1990;62(3):244–78.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Li X, Takahashi M, Kushida K, Inoue T. The preventive and interventional effects of raloxifene analog (LY117018HC1) on osteopenia in ovariectomized rats. Bone Miner Res. 1998;13:1005–10.CrossRefGoogle Scholar
  66. 66.
    Diaz Curiel M, Calero JA, Guerrero R, Gala J, Gazapo R, de la Piedra C. Effects of LY-117018 HC1 on bone remodeling and mineral density in the oophorectomized rat. Am J Obstet Gynecol. 1998;178:320–5.CrossRefGoogle Scholar
  67. 67.
    Buzdar A, O’Shaughnessy JA, Booser DJ, Pippen JE Jr, Jones SE, Munster PN, et al. Phase 11, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. J Clin Oncol. 2003;21:1007–14.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Baselga J, Llombart-Cussac A, Bellet M, Guillem-Porta V, Enas N, Krejcy K, et al. Randomized, double-blind, multicenter trial comparing two doses of arzoxifene (LY353381) in hormone-sensitive advanced or metastatic breast cancer patients. Ann Oncol. 2003;14:1383–90.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Cummings SR, McClung M, Reginster JY, Cox D, Mitlak B, Stock J, et al. Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res. 2011;26(2):397–404.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Kendler DL, Palacios S, Cox DA, Stock J, Alam J, Dowsett SA, et al. Arzoxifene versus raloxifene: effect on bone and safety parameters in postmenopausal women with osteoporosis. Osteoporos Int. 2012;23(3):1091–101.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Goldstein SR, Bhattoa HP, Neven P, Cox DA, Dowsett SA, Alam J, et al. Gynecologic effects of arzoxifene in postmenopausal women with osteoporosis or low bone mass. Menopause. 2012;19(1):41–7.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Miller CP, Collini MD, Trail BD, Harris HA, Kharode YP, Marzolf JT, et al. Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem. 2001;44:1654–7.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Komm BS, Lyttle CR. Developing SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann N Y Acad Sci. 2001;949:317–26.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology. 2005;146(9):3999–4008.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Ronkin S, Clarke L, Boudes P, Constantine G. TSE-124, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose-related fashion. J Bone Miner Res. 2001;16(Suppl):S413.Google Scholar
  76. 76.
    Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res. 2008;23:525–35.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo- and active-controlled clinical trial. J Bone Miner Res. 2008;23:1923–34.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Silverman SL, Chines AA, Kendler DL, Kung AW, Teglbjærg CS, Felsenberg D, et al.; for the Bazedoxifene Study Group. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int. 2012;23(1):351–63.Google Scholar
  79. 79.
    Palacios S, Silverman SL, de Villiers TJ, Levine AB, Goemaere S, Brown JP, et al.; Bazedoxifene Study Group. A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: effects on bone density and fracture. Menopause. 2015;22(8):806–13.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Christiansen C, Chesnut CH 3rd, Adachi JD, Brown JP, Fernandes CE, Kung AW, et al. Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord. 2010;11:130.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    De Villiers TJ, Chines AA, Palacios S, Lips P, Sawicki AZ, Levine AB, et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int. 2011;22(2):567–76.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Palacios S, de Villiers TJ, Nardone Fde C, Levine AB, Williams R, Hines T, et al.; BZA Study Group. Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study. Maturitas. 2013;76(1):81–7.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Lobo RA, Pinkerton JV, Gass ML, Dorin MH, Ronkin S, Pickar JH, et al. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril. 2009;92(3):1025–38.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Palacios S, Ríos M. A bazedoxifene/conjugated estrogens combination for the treatment of the vasomotor symptoms associated with menopause and for prevention of osteoporosis in postmenopausal women. Drugs Today (Barc). 2015;51(2):107–16.CrossRefGoogle Scholar
  85. 85.
    Ke HZ, Paralkar VM, Grasser WA, Crawford DT, Qi H, Simmons H, et al. Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus, and body composition in rat models. Endocrinology. 1998;139:2068–76.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Maeda T, Ke HZ, Simmons H, Thompson D. Lasofoxifene, a next generation estrogen receptor modulator: preclinical studies. Clin Calcium. 2004;14(10):85–93.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Ke HZ, Foley GL, Simmons HA, Shen V, Thompson DD. Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats. Endocrinology. 2004;145(4):1996–2005.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    FABLYN® (lasofoxifene tartrate) 0.5 mg tablets, NDA22–242, Reproductive Health Drugs Advisory Committee Briefing Document. 2008. 4381b1-02-Pfizer.pdf. Accessed 25 Feb 2011.
  89. 89.
    Fablyn® (lasofoxifene tartrate) summary of product characteristics. Pfizer. Final Summary Minutes, Advisory Committee for Reproductive Health Drugs Meeting. 2008. Accessed 25 Mar 2011.
  90. 90.
    Cummings SR, Ensrud K, Delmas PD, LaCroix AZ, Vukicevic S, Reid DM, et al.; PEARL Study Investigators. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010;362(8):686–96.Google Scholar
  91. 91.
    LaCroix AZ, Powles T, Osborne CK, Wolter K, Thompson JR, Thompson D, et al.; PEARL Investigators. Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst. 2010;102(22):1706–15.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Instituto Palacios de Salud y Medicina de la MujerMadridSpain

Personalised recommendations