Selective estrogen receptor modulators: The future in menopausal treatment

Minerva Ginecologica

Volumn 63, Issue 3, 2011, Pages 275-286

  Palacios, S ^a  

^a Palacios Institute of Woman's Health   (Spain)

Author keywords

Hormone replacement therapy; Menopause; Selective estrogen receptor modulators

Indexed keywords

BAZEDOXIFENE; BENZOTHIOPHENE; CONJUGATED ESTROGEN; LASOFOXIFENE; OSPEMIFENE; PLACEBO; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN;

BONE TUMOR; BREAST CANCER; CARDIOVASCULAR DISEASE; CEREBROVASCULAR DISEASE; DRUG APPROVAL; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG METABOLISM; ENDOMETRIUM CANCER; FRACTURE; HORMONAL THERAPY; HOT FLUSH; HUMAN; ISCHEMIC HEART DISEASE; LEG CRAMP; LIPID BLOOD LEVEL; MENOPAUSAL SYNDROME; NONHUMAN; POSTMENOPAUSE OSTEOPOROSIS; REVIEW; VAGINA ATROPHY; VENOUS THROMBOEMBOLISM;

FEMALE; FORECASTING; HUMANS; INDOLES; MENOPAUSE; PYRROLIDINES; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TETRAHYDRONAPHTHALENES;

EID: 79960994879     PISSN: 00264784     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (76)

1. Demography and population .Statistics, data and indicators [Internet]. Available from www.oecd.org [cited 2011, Mar 25].
2. Oldenhave A, Jaszmann LJ, Haspels AA, Everaerd WT. Impact of climacteric on well-being. A survey based on 5213 women 39 to 60 years old. Am J Obstet Gynecol 1993;168:772-80. (Pubitemid 23095992)
3. Palacios S. Advances in hormone replacement therapy: making the menopause manageable. BMC Womens Health 2008;8:22.
4. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA 2002;288:872-81.
5. Hsia J, Simon JA, Lin F, Applegate WB, Vogt MT, Hunninghake D et al. Peripheral arterial disease in randomized trial of estrogen with progestin in women with coronary heart disease: the Heart and Estrogen/Progestin Replacement Study. Circulation 2000;102:2228-32.
6. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.
7. Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society. North American Menopause Society.Menopause 2010;17:242-55.
8. Gompel A, Barlow D, Rozenberg S, Skouby SO; EMAS Executive Committee. The EMAS 2006/2007 update on clinical recommendations on postmenopausal hormone therapy. Maturitas 2007;56:227-9.
9. Naftolin F, Schneider HP, Sturdee DW, Birkhäuser M, Brincat MP, Gambacciani M et al. Executive Committee of the International Menopause Society. Guidelines for hormone treatment of women in the menopausal transition and beyond. Climacteric 2004;7:333-94.
10. Vegter S, Kölling P, Töben M, Visser ST, de Jong-van den Berg LT. Replacing hormone therapy - is the decline in prescribing sustained, and are nonhormonal drugs substituted? Menopause 2009;16:329-35.
11. Farley JF, Blalock SJ, Cline RR. Effect of the women's health initiative on prescription anti-osteoporosis medication utilization. Osteoporos Int 2008;19:1603-12.
12. Palacios S. The future of the new selective estrogen receptor modulators. Menopause Int 2007;13:27-34. (Pubitemid 46692067)
13. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators-mechanisms of action and application to clinical practice. N Engl J Med 2003;348:618-29. (Pubitemid 36210865)
14. Palacios S. Efficacy and safety of bazedoxifene, a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis. Curr Med Res Opin 2010;26:1553-63.
15. Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB. Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv 2008;63:163-81. (Pubitemid 351612435)
16. Palacios S. Third generation SERMs: anything new? Maturitas 2010;67:101-2.
17. Nolvadex Adjuvant Trial Organization. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer; interim analysis at four years by Nolvadex Adjuvant Trial Organization. Lancet 1983;1:257-61.
18. Early Breast Cancer Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomized trials. Lancet 1998;351:1.451-1.467
19. Ward HW. Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J 1973;1:13-4
20. Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, Jordan VC et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992 ;326:852-6.
21. Fisher B and the NSABBP investigators. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1.371-1.388.
22. Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomized chemoprevention trial. Lancet 1998;352:98-101. (Pubitemid 28321321)
23. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomisez trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 1998;352:93-97. (Pubitemid 28321320)
24. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med 2009;151:703-15.
25. Seeman E, Crans GG, Diez-Perez A, Pinette KV, Delmas PD. Anti-vertebral fracture efficacy of raloxifene:a meta-analysis. Osteoporos Int 2006;17:313-6.
26. Siris ES, Harris ST, Eastell R, Zanchetta JR, Goemaere S, Diez-Perez A et al. Continuing Outcomes Relevant to Evista (CORE) InvestigatorsSkeletal effects of raloxifene after 8 years:results from the continuing outcomes relevant to Evista (CORE) study. J Bone Miner Res 2005;20:1514-24.
27. 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;355:125-37. (Pubitemid 44050394)
28. Mosca L, Grady D, Barrett-Connor E, Collins P, Wenger N, Abramson BL et al. Effect of raloxifene on stroke and venous thromboembolism according to subgroups in postmenopausal women at increased risk of coronary heart disease. Stroke 2009;40:147-55.
29. 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;295:2727-41.
30. Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146:3999-4008. (Pubitemid 41175771)
31. Peano BJ, Crabtree JS, Komm BS, Winneker RC, Harris HA. Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 2009;150:1897-903.
32. Miller CP, Collini MD, Tran 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.
33. Ermer J, McKeand W, Sullivan P, Parker V, and Orczyk G. Bazedoxifene acetate dose proportionality in healthy, postmenopausal women. Clin Pharmacol Ther 2003;73.P46.
34. Chandrasekaran A, McKeand WE, Sullivan P, DeMaio W, Stoltz R, Scatina J. Metabolic disposition of [14C] bazedoxifene in healthy postmenopausal women. Drug Metab Dispos 2009;37:1219-25.
35. Ronkin S, Clarke L. TSE-424, a novel tissue selective estrogen, reduces biochemical indices of bone metabolism in a dose related fashion [abstract SU437]. J Bone Miner Res 2001;16(Suppl 1):S413.
36. Ronkin S, Northington R, Baracat E, Nunes MG, Archer DF, Constantine G et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005;105:1397-404. (Pubitemid 40734275)
37. 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. (Pubitemid 351501893)
38. 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.
39. 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.
40. Chines AA, Zanchetta JR, Genant K, Kendler DL, Rio de Loza A, Kung AW et al. Sustained efficacy of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of 5-years, randomized, placebo-controlled study IOF-ECCEO10-ABS-387. Mars 2010
41. 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;22:567-76.
42. Rosati RL, Da Silva Jardine P, Cameron KO, Thompson DD, Ke HZ, Toler SM et al. Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene. J Med Chem 1998;41:2928-31.
43. Ke HZ, Paralkar VM, Grasser WA, Crawford DT, Qi H, Simmons HA 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.
44. 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;145:1996-2005. (Pubitemid 38402409)
45. Cohen LA, Pittman B, Wang CX, Aliaga C, Yu L, Moyer JD. LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model. Cancer Res 2001;61:8683-8.
46. Gardner M, Taylor A, Wei G, Calcagni A Jr, Duncan B, Milton A. Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women. J Clin Pharmacol 2006;46:52-8. (Pubitemid 43021713)
47. Gennari L. Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy. Expert Opin Pharmacother 2009;10:2209-20.
48. McClung MR, Siris E, Cummings S, Bolognese M, Ettinger M, Moffett A et al. Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene. Menopause 2006;13:377-86.
49. FABLYN® (lasofoxifene tartrate) 0.5mgtablets, NDA22-242, Reproduc- 827 tive HealthDrugsAdvisoryCommitteeBriefingDocument. September8, 828 2008. Availableat:http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-8294381b1-02- Pfizer.pdf. Accessed on February 25, 2011.
50. Fablyn® (lasofoxifene tartrate) Summary of Product Characteristics. Pfizer. Final Summary Minutes, Advisory committee fo rreproductive health drugs meeting [Internet]. September 8, 2008. Available from: http://www.fda gov/ohrms/dockets/ac/08/minutes/2008-4381m1-final.pdf [cited 2011, Mar 25].
51. 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;362:686-96.
52. LaCroix AZ, Powles T, Osborne CK, Wolter K, Thompson JR, Thompson DD et al. PEARL Investigators Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women J Natl Cancer Inst. 2010 Nov 17;102:1706-15.
53. Final Summary Minutes, Advisory committee for reproductive health drugs meeting (Internet). Available from: http://www.fda.gov/ohrms/dockets/ac/08/ minutes/2008-4381m1-final.pdf [cited 2011, Mar 25].
54. Gennari L, Merlotti D, Valleggi F, Nuti R. Ospemifene use in postmenopausal women. Expert Opin Investig Drugs 2009;18:839-49.
55. Qiang Q, Zhengt H, Dahlund J, Laine A, Cockcroft N, Peng Z et al. Selective estrogenic effects of anovel triphenylethylene compound, FC1271a, on bone, cholesterol levels andreproductive tissues in intact and ovariectomized rats. Endocrinology 2000;141:809-20. (Pubitemid 32250507)
56. Komi J, Heikkinen J, Rutanen EM, Halonen K, Lammintausta R, Ylikorkala O. Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women.Gynecol Endocrinol 2004;18:152-8.
57. Taras TL, Wurz GT, DeGregorio MW. In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer. J Steroid Biochem Mol Biol 2001;77:271-9.
58. Michael H, Härkönen PL, Kangas L, Väänänen HK, Hentunen TA. Differential effects of selective oestrogen receptor modulators (SERMs) tamoxifen, ospemifene and raloxifene on human osteoclasts in vitro. Br J Pharmacol 2007;151:384-95. (Pubitemid 46842673)
59. DeGregorio MW, Wurz GT, Taras TL, Erkkola RU, Halonen KH, Huupponen RK. Pharmacokinetics of (deaminohydroxy)toremifene in humans: a new, selective estrogen-receptormodulator. Eur J Clin Pharmacol 2000;56:469-75.
60. Voipio SK, Komi J, Halonen K, Halonen K, DeGregorio MW, Erkkola RU. Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas 2002;43:207-14.
61. Rutanen EM, Heikkinen J, Halonen K, Komi J, Lammintausta R, Ylikorkala O. Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women:A double-blind, randomized trial. Menopause 2003;10:433-9.
62. Komi J, Lankinen KS, DeGregorio M, Heikkinen J, Saarikoski S, Tuppurainen M et al. Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women J Bone Miner Metab 2006;24:314-8.
63. Komi J, Heikkinen J, Rutanen EM, Halonen K, Lammintausta R, Ylikorkala O. Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women. Gynecol Endocrinol 2004;18:152-8.
64. 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;12:202-9. (Pubitemid 40464289)
65. Bachmann GA, Komi JO; Ospemifene Study Group. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study. Menopause 2010;17:480-6.
66. QuatrxPharmaceuticalsReportsPositiveResultsofaSecondPivotal Phase 3Clinical Study for Ophena TM (Ospemiphene Tablets) in Treatment of Postmenopausal Vaginal Atrophy [Internet]. Available from http://www.quatrx.com/ news/091009.htm. [cited on 2011, Mar 25].
67. QuatrxAnnouncesFurtherPositivePhase3 Results for Ophena TM (Ospemiphene Tablets) in Treatment of-Postmenopausal Vaginal Atrophy [Internet]. Available from http://www.quatrx.corn/news/072909.htm [cited 2011, Mar 25].
68. Gennari L. Ospemifene Hormos. Curr Opin Investig Drugs 2004;5:448-55.
69. Pinkerton JV, Stovall DW. Bazedoxifene when paired with conjugated estrogens is a new paradigm for treatment of postmenopausal women. Expert Opin Investig Drugs 2010;19:1613-21.
70. Pickar JH, MacNeil T, Ohleth K. SERMs: progress and future perspectives. Maturitas 2010;67:129-38.
71. Chen L, Sato M, Inoko H, Kimura M. Molecular cloning and analysis of novel cDNAs specifically expressed in adult mouse testes. Biochem Biophys Res Commun 1997;240:261-8.
72. 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;92:1025-38.
73. Archer DF, Lewis V, Carr BR, Olivier S, Pickar JH. Bazedoxifene/ conjugated estrogens (BZA/CE):incidence of uterine bleeding in postmenopausal women. Fertil Steril 2009;92:1039-44.
74. Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009;92:1045-52.
75. Pinkerton JV, Utian WH, Constantine GD, Olivier S, Pickar JH. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens:a randomized, controlled trial. Menopause 2009;16:1116-24.
76. Kagan R, Williams RS, Pan K, Mirkin S, Pickar JH. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause 2010;17:281-9.