Pharmacology and clinical applications of selective estrogen receptor modulators

Climacteric

Volumn 12, Issue 3, 2009, Pages 188-205

  Nath, A ^a   Sitruk Ware, R ^b  

^a POPULATION COUNCIL   (United States)

^b ROCKEFELLER UNIVERSITY   (United States)

Author keywords

Antiestrogen; Breast Cancer; Osteoporosis; Postmenopause

Indexed keywords

4 [4 METHYL 2 [4 [2 (1 PIPERIDINYL)ETHOXY]PHENYL] 7 PIVALOYLOXY 2H 1 BENZOPYRAN 3 YLPHENYL] PIVALATE; ANASTROZOLE; ARZOXIFENE; BAZEDOXIFENE; BROMOCRIPTINE; CENTCHROMAN; CLOMIFENE; CONJUGATED ESTROGEN; DANAZOL; DROLOXIFENE; DT 56A; ESTETROL; ESTRADIOL; FULVESTRANT; HMR 3339; IDOXIFENE; LASOFOXIFENE; OSPEMIFENE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; TD 56A; TOREMIFENE; UNCLASSIFIED DRUG; CHOLESTEROL;

ARTHRALGIA; BACKACHE; BONE; BREAST; BREAST CANCER; BREAST DISEASE; CARDIOVASCULAR DISEASE; CATARACT; CLINICAL TRIAL; COGNITIVE DEFECT; DEEP VEIN THROMBOSIS; DEMENTIA; DEPRESSION; DIZZINESS; DRUG ABSORPTION; DRUG ERUPTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DYSPNEA; ENDOMETRIUM CANCER; ENDOMETRIUM CARCINOMA; ENDOMETRIUM HYPERPLASIA; ENDOMETRIUM POLYP; ENDOMETRIUM TUMOR; EYE DISEASE; EYE TOXICITY; FEMALE INFERTILITY; FIBROADENOMA; GYNECOMASTIA; HEADACHE; HEART PROTECTION; HOT FLUSH; HUMAN; INFECTION; LEG CRAMP; LUNG EMBOLISM; LUTEAL PHASE; MALE INFERTILITY; MASTALGIA; MENOPAUSAL SYNDROME; MENOPAUSE; MOOD; MULTIPLE PREGNANCY; MUSCLE CRAMP; NAUSEA; NAUSEA AND VOMITING; NONHUMAN; OSTEOPOROSIS; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SEXUAL DYSFUNCTION; SIDE EFFECT; STOMACH ADENOCARCINOMA; STROKE; THROMBOCYTOPENIA; THROMBOEMBOLISM; UROGENITAL TRACT DISEASE; UTERINE CERVIX MUCUS; UTERUS; UTERUS PROLAPSE; VAGINA ATROPHY; VAGINA DISCHARGE; VENOUS THROMBOEMBOLISM; VERTEBRA FRACTURE; VISUAL DISORDER; ATROPHY; BLOOD; CHEMICAL STRUCTURE; CHEMICALLY INDUCED DISORDER; CHEMISTRY; COGNITION; DRUG EFFECT; FEMALE; HEADACHE AND FACIAL PAIN; INFERTILITY; MALE; NEOPLASM; PATHOLOGY; POSTMENOPAUSE OSTEOPOROSIS; UTERUS DISEASE; VAGINA;

ATROPHY; CHOLESTEROL; COGNITION; EYE DISEASES; FEMALE; GYNECOMASTIA; HEADACHE DISORDERS; HUMANS; INFERTILITY; MALE; MENOPAUSE; MOLECULAR STRUCTURE; NEOPLASMS; OSTEOPOROSIS, POSTMENOPAUSAL; SELECTIVE ESTROGEN RECEPTOR MODULATORS; THROMBOCYTOPENIA; UTERINE DISEASES; VAGINA; VENOUS THROMBOEMBOLISM;

EID: 68949108335     PISSN: 13697137     EISSN: 14730804     Source Type: Journal    
DOI: 10.1080/13697130802657896     Document Type: Review

References (169)

1. Riggs BL, Hartmann LC. Selective estrogenreceptor modulators - mechanisms of action and application to clinical practice. N Engl J Med 2003;348:618-629
2. Rossouw JW, Anderson GL, Prentice RL, et al. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in health postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333
3. Smith CL, O'Malley BW. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004;5:45-71
4. Meegan MJ, Lloyd DG. Advances in the science of estrogen receptor modulation. Curr Med Chem 2003;10:181-210
5. Bryant H. Selective estrogen receptor modulators. Rev Endocr Metab Dis 2002;3:231-241
6. Patankar SS, Kaore SB, Sawane MV, Mishra NV, Deshkar AM. Effect of clomiphene citrate on sperm density in male partners of infertile couples. Ind J Physiol Pharmacol 2007; 51:195-198
7. Uyar Y, Koltan SO, Pögün S, Vatansever S, Caglar H. The effect of clomiphene citrate on osteoporosis in ovariectomized rats. Arch Gynecol Obstet 2008;278:107-114
8. Rozen TD, Saper JR, Sheftell FD, Dodick DW. Clomiphene citrate as a new treatment for SUNCT: hormonal manipulation for hypothalamic- influenced trigeminal autonomic cephalalgias. Headache 2005;45:754-756
9. Rozen T. Clomiphene citrate for treatment refractory chronic cluster headache. Headache 2008;48:286-290
10. Asch RH, Greenblatt RB. Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. J Reprod Med 1976;17: 175-180
11. Adashi EY. Clomiphene citrate: The case for a monoisometric preparation. Baillieres Clin Obstet Gynaecol 1993;7:331-347
12. Derman SG, Adashi EY. Adverse effects of fertility drugs. Drug Safety 1994;11:408-421
13. Legro RS, Barnhart HX, Schlaff WD. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356:551-566
14. Osborn CK. Drug therapy: tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339:1609-1618
15. Buckley MM, Goa KL. Tamoxifen: A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic uses. Drugs 1989;37: 451-490
16. Langhey Fahey SM, Jordan VC, Fritz NF, Robinson SP, Waters D, Tormey DC. Clinical pharmacology and endocrinology of long term tamoxifen therapy. In Jordan VC, ed. Long Term Tamoxifen Treatment for Breast Cancer. Madinson: University of Wisconsin Press, 1994. 27-56.
17. Lein EA, Solheim E, Ueland PM. Distribution of tamoxifen and its metabolites in rat and human tissues during steady state treatment. Cancer Research 1991;51:4837-4844
18. Osborne CK, Elledge RM, Fuqua SAW. Estrogen receptors in breast cancer therapy. Sci Med 1996;3:32-41
19. Arteaga CL, Osborne CK. Growth factors as mediators of estrogen/antiestrogen action in human breast cancer cells. In Lippman ME, Dickson RB, eds. Regulatory Mechanisms in Breast Cancer: Advances in Cellular and Molecular Biology of Breast Cancer. Boston: Kluwer Academic, 1991:289-304.
20. The Early Breast Cancer Trialists Collaborative Group. Tamoxifen for early breast cancer: An overview of randomized trials. Lancet 1998;351: 1451-1467
21. Controlled trial of tamoxifen as a single adjuvant agent in the management of early breast cancer. Novadex adjuvant trial organization. Br J Cancer 1988;57:608-611
22. Fisher B, Redmond C, Brown A, et al. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5 year results from the National Surgical Adjuvant Breast and Bowel Project Trials. J Clin Oncol 1986;4:459-471 (Pubitemid 16117934)
23. The Early Breast Cancer Trialists' Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy: 133 randomised trials involving 31 000 recurrences and 24 000 deaths among 75 000 women. Lancet 1992;339:1-15
24. Boccardo F, Amoroso D, Rubagotti A, et al. Endocrine therapy of breast cancer: The experience of the Italian Cooperative Group for Chemohormonal Therapy of Early Breast Cancer (GROCTA). Ann N Y Acad Sci 1993;698: 318-329
25. Kaufmann M, Jonat W, Able U, et al. Adjuvant randomized trials of doxorubicin/ cyclophosphamide versus doxorubicin/ cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer. J Clin Oncol 1993; 11:454-460
26. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 1997;89:1673-1682
27. Rivkin SE, Green S, Metch B, et al. Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive and estrogen receptor-positive breast cancer patients: A Southwest Oncology Group study. J Clin Oncol 1994; 12:2078-2085
28. Pritchard KI, Paterson AH, Fine S, et al. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: A report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1997;15:2302-2311
29. Fisher B, Redmond C, Legault-Poisson S, et al. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: Results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol 1990;8:1005-1018
30. Saez RA, Osborne CK. Hormonal treatment of advanced breast cancer. In Kennedy BJ, ed. Current Clinical Oncology, Vol.1 Breast Cancer. New York: Alan R. Liss, 1989:163-172
31. Catherino WH, Jordan VC. A risk benefit assessment of tamoxifen therapy. Drug Saf 1993;8:381-397
32. Castrellon AB, Glück S. Chemoprevention of breast cancer. Expert Rev Anti Cancer Ther 2008;8:443-452
33. Fisher B, Constantino JP, Wickerham DL, 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;90:1371-1388
34. Derman O, Kanbur NO, Kutluk T. Tamoxifen treatment for pubertal gynecomastia. Int J Adolesc Med Health 2003;15:359-363
35. Hanavadi S, Banerjee D, Monypenny IJ, Mansel RE. The role of tamoxifen in the management of gynaecomastia. Breast 2006; 15:276-280
36. Khan HN, Rampaul R, Blamey RW. Management of physiological gynecomastia with tamoxifen. Breast 2004;13:61-65
37. Devoto CE, Madariaga AM, Lioi CX, Mardones N. Influence of size and duration of gynecomastia on its response to treatment with tamoxifen. Revista Medica de' Chile 2007;135: 1558-1565
38. Parker LN, Gray DR, Lai MK, Levin ER. Treatment of gynecomastia with tamoxifen: A double-blind crossover study. Metabolism 1986; 35:705-708
39. Li CP, Lee FY, Hwang SJ, et al. Treatment of mastalgia with tamoxifen in male patients with liver cirrhosis: A randomized crossover study. Am J Gastroenterol 2000;95:1051-1055
40. Love RR, Mazess RB, Barden HS, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992;326:852-856
41. Williams JK, Wagner JD, Li Z, Golden DL, Adams MR. Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. Arterioscler Thromb Vasc Biol 1997;17:403-408
42. Waltman NL, Ott CD, Twiss JJ, Gross GJ, Lindsey AM, Moore TE. Bone mineral density and bone turnover in postmenopausal women treated for breast cancer. Cancer Nursing 2008; 31:182-190
43. Gonnelli S, Cadirni A, Caffarelli C, et al. Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane. Bone 2007;40:205-210
44. Kristensen B, Ejlertsen B, Mouridsen HT, Andersen KW, Lauritzen JB. Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen. Breast Cancer Res Treat 1996;39:321-326
45. Kristensen B, Ejlertsen B, Dalgaard P, et al. Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: A randomized study. J Clin Oncol 1994;12: 992-997
46. Rutqvist LE, Mattsson A. Cardiac and thromboembolic morbidity among post-menopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen: The Stockholm Breast Cancer Study Group. J Natl Cancer Inst 1993;85:1398-1406
47. Bilimoria MM, Jordan VC, Morrow M. Additional benefits of tamoxifen for post-menopausal patients. In Jordon VC, ed. Tamoxifen: A Guide for Clinicians and Patients. Huntington, NY: PRR, Inc, 1996;75-89.
48. Ek RO, Yildiz Y, Cecen S, Yenisey C, Kavak T. Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats. Mol Cell Biochem 2008;308: 227-235
49. Gielen SC, Santegoets LA, Hanifi- Moghaddam P, Burger CW, Blok LJ. Signaling by estrogens and tamoxifen in the human endometrium. J Steroid Biochem Mol Biol 2008;109:219-223
50. Gorodeski GI, Beery R, Lunenfeld B, Geier A. Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. Fertil Steril 1992;57:320-327
51. Stewart HJ, Prescott RJ, Forrest AP. Scottish Adjuvant Tamoxifen trial: A randomized study updated to 15 years. J Natl Cancer Inst 2001;93: 456-462
52. Erdemoglu E, Güney M, Keskin B, Mungan T. Tamoxifen and giant endometrial polyp. Eur J Gynecol Oncol 2008;29:198-199
53. Dede M, GezginçK, Ulubay M, Alanbay I, Güran S, Yenen M. A breast cancer patient with pelvic and gastric malignancy after adjuvant tamoxifen treatment for breast cancer. Eur J Gynecol Oncol 2008;29:200
54. Matsuyama Y, Tominaga T, Nomura Y, et al. Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan. Ann Oncol 2000;11: 1537-1543
55. Chandanos E, Lindblad M, Rubio CA, et al. Tamoxifen exposure in relation to gastric adenocarcinoma development. Eur J Cancer 2008;44:1007-1014
56. Fisher B, Costantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptorpositive tumors. N Engl J Med 1989;320: 479-484 (Pubitemid 19062522)
57. Fisher B, Dignam J, Bryant J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996;88:1529-1542
58. Bao T, Davidson NE. Adjuvant endocrine therapy for premenopausal women with early breast cancer. Breast Cancer Res 2007;9:115
59. Love RR, Cameron L, Connell BL, Leventhal H. Symptoms associated with tamoxifen treatment in post menopausal women. Arch Intern Med 1991;151:1842-1847
60. Saphner T, Tormey DC, Gray R. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J Clin Oncol 1991;9:286-294
61. McDonald CC, Alexander FE, Whyte BW, Forrest AP, Stewart HJ. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. The Scottish Cancer Trials Breast Group. BMJ 1995;311:977-980
62. Vogel VG, Constantino JP, Wickerham DL, et al. 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;295:2727-2741
63. Nayfield SG, Gorin MB. Tamoxifen-associated eye disease: A review. J Clin Oncol 1996;14: 1018-1026
64. Gorin MB, Day R, Costantino JP, et al. Long term tamoxifen citrate use and potential ocular toxicity. Am J Ophthalmol 1998;125:493-501
65. Varas-Lorenzo C, Garcia-Rodriguez LA, Cattaruzzi C, Troncon MG, Agostinis L, Perez-Gutthann S. Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: A population based study in Southern Europe. Am J Epidemiol 1998;147: 387-390
66. Yao JC, Thomakos N, McLaughlin P, Buchholz TA, Kudelka AP. Tamoxifen-induced thrombocytopenia. Am J Clin Oncol 1999;22: 529-532
67. Nasiroglu N, Pamukçuoglu M, Abali H, Oksüzoglu B, Uner A, Zengin N. Tamoxifen induced-thrombocytopenia: It does occur. Med Oncol 2007;24:453-454
68. Buzdar AU, Hortobagyi GN. Tamoxifen and toremifene in breast cancer: Comparison of safety and efficacy. J Clin Oncol 1998;26: 348-353
69. Hayes DF, Van Zyl JA, Hacking A, et al. Randomized comparison of tamoxifen and two separate doses of toremifene in post menopausal patients with metastatic breast cancer. J Clin Oncol 1995;13:2556-2566
70. Lewis-Wambi JS, Jordan VC. Treatment of postmenopausal breast cancer with selective estrogen receptor modulators (SERMs). Breast Dis 2005-2006;24:93-105
71. Dodwell D, Wardley A, Johnston S. Postmenopausal advanced breast cancer: options for therapy after tamoxifen and aromatase inhibitors. Breast 2006;15:584-594
72. Yamamoto Y, Kawazoe T, Iwase H. Experience of high-dose toremifene treatment for postmenopausal women with metastatic breast cancer. Gan To Kagaku Ryoho 2005;32:1415-1419
73. Smith MR, Malkowicz SB, Chu F, et al. Toremifene improves lipid profiles in men receiving androgen-deprivation therapy for prostate cancer: Interim analysis of a multicenter phase III study. J Clin Oncol 2008;26:1824-1829
74. Joensuu H, Holli K, Oksanen H, Valavaara R. Serum lipid levels during and after adjuvant toremifene or tamoxifen therapy for breast cancer. Breast Cancer Res Treat 2000;63: 225-234
75. Erkkola R, Mattila L, Powles T, 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 preand post-menopausal women. Breast Cancer Res Treat 2005;93:277-287
76. Raghow S, Hooshdaran MZ, Katiyar S, Steiner MS. Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model. Cancer Res 2002;62:1370-1376
77. Price D, Stein B, Sieber P, et al. Toremifene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia: Results of a double-blind, placebo controlled, phase IIB clinical trial. J Urol 2006;176:965-970
78. Smith MR, Malkowicz SB, Chu F. Toremifene increases bone mineral density in men receiving androgen deprivation therapy for prostate cancer: Interim analysis of a multicenter phase 3 clinical study. J Urol 2008;179:152-155
79. Marttunen MB, Hietanen P, Tiitinen A, Ylikorkala O. Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients. J Clin Endocrinol Metab 1998; 83:1158-1162
80. Tiitenen A, Nikander E, Hietanen P, Metsää- Heikkila M, Ylikorkala O. Changes in bone mineral density during and after 3 years' use of tamoxifen or toremifene. Maturitas 2004;48: 321-327
81. O'Regan RM, Cisneros GM, England GM, et al. Effects of the antiestrogens tamoxifene, toremifene and ICI 182,780 on endometrial cancer growth. J Natl Cancer Inst 1998;90:1552-1555
82. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med 2001; 344:1997-2008
83. Harvey HA, Kimura M, Hajba A. Toremifene: An evaluation of its safety profile. Breast 2006; 15:142-157
84. Gersanovich M, Garin A, Baltina D, et al. A Phase III comparison of two toremifene doses to tamoxifen in post menopausal women with advanced breast cancer. Eastern European Study Group. Breast Cancer Res Treat 1997;45: 251-262
85. Maenpaa JU, Ala-Fossi SL. Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. Drugs Aging 1997;11:261-270
86. Huang Y, Shen Y, Feng Y, Cao L, Leng Y. Antiimplantation effect of droloxifene in rats and its relationship with anti-estrogenic activity. Acta Pharmacol Sin 2005;26:1243-1247
87. Johnston SR. Endocrine manipulation in advanced breast cancer: Recent advances with SERM therapies. Clin Cancer Res 2001;7: 4376-4387
88. Buzdar A, Hayes D, El-Khoudary A, Yan S. Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PR-positive advanced breast cancer. Breast Cancer Res Treat 2002;73:161-175
89. Ke HZ, Crawford DT, Qi H. Droloxifene does not blunt bone anabolic effects of prostaglandin E2, but maintains prostaglandin E2-restored bone in aged, ovariectomized rats. Bone 1999; 24:41-47
90. Ke HZ, Chen HK, Simmons HA. Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum cholesterol, and uterine histology in the ovariectomized rat model. Bone 1997; 20:31-39
91. Herrington DM, Pusser BE, Riley WA, et al. Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women. Arterioscler Thromb Vasc Biol 2000;20:1606-1612
92. Haarstad H, Lønning PE, Gundersen S, Wist E, Raabe N, Kvinnsland S. Influence of droloxifene on metastatic breast cancer as firstline endocrine treatment. Acta Oncol 1998;37: 365-368
93. McCague R, Parr IB, Haynes BP. Metabolism of the 4-iodo derivative of tamoxifen by isolated rat hepatocytes: demonstration that the iodine atom reduces metabolic conversion and identifi- cation of four metabolites. Biochem Pharmacol 1990;40:2277-2283
94. Nuttall ME, Bradbeer JN, Stroup GB, et al. Idoxifene: A novel selective estrogen receptor modulator prevents bone loss and lowers cholesterol levels in ovariectomized rats and decreases uterine weight in intact rats. Endocrinology 1998;139:5224-5234
95. Johnston SR, Gumbrell LA, Evans TR. A Cancer Research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen. Cancer Chemother Pharmacol 2004;53:341-348
96. Arpino G, Nair Krishnan M, Doval Dinesh C, Bardou VJ, Clark GM, Elledge RM. Idoxifene versus tamoxifen: A randomized comparison in postmenopausal patients with metastatic breast cancer. Ann Oncol 2003;14:233-241
97. Fleischer AC, Wheeler JE, Yeh IT, Kravitz B, Jensen C, MacDonald B. Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene. J Ultrasound Med 1999;18:503-512
98. Albertazzi P, Sharma S. Urogenital effects of selective estrogen receptor modulators: A systematic review. Climacteric 2005;8:214-220
99. Komi J, Lankinen KS, DeGregorio M, Heikkinen J, Saarikoski S, Tuppurainen M. Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women. J Bone Miner Metab 2006;24: 314-318
100. 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; 18:152-158
101. Voipio SK, Komi J, Kangas L, 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;43:207-214
102. 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 doubleblind, randomized trial. Menopause 2003;10: 433-439
103. Wurz GT, Read KC, Marchisano-Karpman C, et al. Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice. J Steroid Biochem Mol Biol 2005;97:230-240
104. Johnston CC Jr, Bjarnason NH, Cohen FJ, et al. Long term effects of raloxifene on bone mineral density, bone turnover and serum lipids in early post menopausal women: 3 year data from two double blind, randomized placebo controlled trials. Arch Intern Med 2000;160:3444-3450
105. 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;10:330-336
106. Ettinger B, Black DM, Mitlak BH. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 1999;282:637-645
107. Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in post menopausal women. N Engl J Med 2006;355:125-137
108. Ishani A, Blackwell T, Jamal SA, et al. MORE Investigators. The effect of raloxifene treatment in postmenopausal women with CKD. J Am Soc Nephrol 2008;19:1430-1438
109. Yaffe K, Krueger K, Cummings SR, et al. Effect of raloxifene on prevention of dementia and cognitive impairment in older women: The Multiple Outcomes of Raloxifene Evaluation (MORE) randomized trial. Am J Psychiatry 2005;162:683-690
110. Lippman ME, Krueger KA, Eckert S, et al. Indicators of life time estrogen exposure: Effect on breast cancer incidence and interaction with raloxifene therapy in the Multiple Outcomes of Raloxifene Evaluation study participants. J Clin Oncol 2001;19:3111-3116
111. Cauley JA, Norton L, Lippmann ME, et al. Continued breast cancer risk reduction in post menopausal women treated with raloxifene: 4-years results from the MORE trial. Multiple Outcomes of Reloxifene Evaluation. Breast Cancer Res Treat 2001;65:125-134
112. Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast cancer incidence in post menopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004;96: 1751-1761
113. Wen-Ling L, Ming-Huei C, Hsiang-Tai C, Peng-Hui W. The role of selective estrogen receptor modulators on breast cancer: from tamoxifen to raloxifene. Taiwan J Obstet Gynecol 2008;47:24-31
114. Vogel VG, Constantino JP, Wickerham DL, et al. 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;295:2727-2741
115. Boss SM, Huster WJ, Neild JA, Glant MD, Eisenhut CC, Draper MW. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol 1997; 177:1458-1464
116. 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;337:1641-1647
117. Barrett-Connor E, Grady D, Sashegyi A, et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: four-year results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 2002;287:847-857
118. Grady D, Ettinger B, Moscarelli E, et al. Safety and adverse effects associated with raloxifene: Multiple outcomes of raloxifene evaluation. Obstet Gynecol 2004;104: 837-844
119. Martino S, Disch D, Dowsett SA, Keech CA, Mershon JL. Safety assessment of raloxifene over eight years in a clinical trial setting. Curr Med Res Opin 2005;21:1441-1452
120. Glusman J, Lu Y, Huster W, et al. Raloxifene effects on climacteric symptoms compared with hormone or estrogen replacement therapy (HRT or ERT). Proceedings of North American Menopause Society, 8th Annual Meeting 1997, abstr, p 65
121. Buzdar A, O'Shaughnessy JA, Booser DJ, et al. Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. J Clin Oncol 2003;21:1007-1014
122. Deshmane V, Krishnamurthy S, Melemed AS, Peterson P, Buzdar AU. Phase III double-blind trial of arzoxifene compared with tamoxifen for locally advanced or metastatic breast cancer. J Clin Oncol 2007;25:4967-4973
123. Liby K, Rendi M. Suh N. et al. The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer. Clin Cancer Res 2006;12:5902-5909
124. Rendi MH, Suh N, Lamph WW, Krajewski S, Reed JC, Heyman RA. The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor beta-dependent apoptosis in breast cancer. Cancer Res 2004; 64:3566-3571
125. Liby K, Rendi M, Suh N, et al. The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer. Clin Cancer Res 2006;12:5902-5909
126. Ma YL, Bryant HU, Zeng Q, et al. Long-term dosing of arzoxifene lowers cholesterol, reduces bone turnover, and preserves bone quality in ovariectomized rats. J Bone Miner Res 2002;17:2256-2264
127. Sato M, Turner CH, Wang T, Adrian MD, Rowley E, Bryant HU. LY353381.HCl: A novel raloxifene analog with improved SERM potency and efficacy in vivo. J Pharmacol Exp Ther 1998;287:1-7
128. Buzdar A, O'Shaughnessy JA, Booser DJ, Pippen JE Jr, Jones SE, Munster PN et al. Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. J Clin Oncol 2003;21:1007-1014
129. Gennari L. Lasofoxifene: A new type of selective estrogen receptor modulator for the treatment of osteoporosis. Drugs Today (Barc) 2006;42:355-367 (Pubitemid 44090110)
130. Rosati RL, Da Silva Jardine P, Cameron KO, et al. Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene. J Med Chem 1998; 41:2928-2931
131. Ke HZ, Paralkar VM, Grasser WA. Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models. Endocrinology 1998;139:2068-2076
132. Gennari L. Lasofoxifene (Pfizer). Curr Opin Investig Drugs 2005;6:1067-1078
133. 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
134. Ke HZ, Qi H, Crawford DT, Chidshey- Frink KL, Simmons HA, Thompson DD. Lasofoxifene (CP-336-156), a selective estrogen receptor modulator, prevents bone loss induced by aging and orchidectomy in the adult rat. Endocrinology 2000;141:1338-1344
135. Fountaine R, Nishizawa Y, Wei G, Dogolo L, Calcagni A, Gardner MJ. Clinical pharmacology of lasofoxifene in Japanese and white postmenopausal women. J Clin Pharmacol 2006;46:693-699 (Pubitemid 43920233)
136. Bramson C, Ouellet D, Roman D, Randinitis E, Gardner MJ. A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment. J Clin Pharmacol 2006;46:29
137. Lee A, Radecki D, Wolter K, et al. Lasofoxifene phase 2 and phase 3 clinical trial design and strategy. J Bone Miner Res 2005;20(Suppl 1): Abstr M384
138. Day W, Martel J, Lee A. Lasofoxifene phase 2 dose response analysis in postmenopausal women. J Bone Miner Res 2005;20(Suppl 1):abstr M385
139. McClung M, Portman D, Emkey R, et al. Comparison of the extraskeletal effects of lasofoxifene and raloxifene. J Bone Miner Res 2004;19(Suppl):abstr SA423
140. Portman DJ, Moffett AH, Bachman GA, West C, Symons J. Lasofoxifene, a selective estrogen receptor modulator, improves objective measures of vaginal atrophy. Obstet Gynecol 2004;103:25-26
141. Davidson M, Moffett A, Welty F, et al. Extraskeletal effects of lasofoxifene on postmenopausal women. J Bone Miner Res 2005;20(Suppl 1):abstr SA428
142. Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM. 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;23:525-535
143. Silverman SL, Christiansen C, Genant HK, 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;23:1923-1934
144. Kharode Y, Bodine PVN, Miller CP, Lyttle CR, Komm BS. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008;149: 6084-6091
145. Nityanand S, et al. Clinical evaluation of centchroman: A new oral contraceptive. In Puri CP, Van Look PFA, eds. Hormone Antagonists for Fertility Regulation. Bombay, India: ISSRF, 1990
146. Dhar A, Srivastava A. Role of centchroman in regression of mastalgia and fibroadenoma. World J Surg 2007;31:1178-1184
147. Narayana Murthy PS, Sengupta S, Sharma S, Singh MM. Effect of ormeloxifene on ovariectomy- induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression. J Steroid Biochem Mol Biol 2006; 100:117-128
148. Labrie F, Champagne P, Labrie C, Roy J, Laverdiè re J, Provencher L. Activity and safety of the antiestrogen EM-800, the orally active precursor of acolbifene, in tamoxifen-resistant breast cancer. J Clin Oncol 2004;22:864-871
149. Martel C, Picard S, Richard V, et al. Prevention of bone loss by EM-800 and raloxifene in the ovariectomized rat. J Steroid Biochem Mol Biol 2000;74:45-56
150. Young OE, Renshaw L, Macaskill EJ, et al. Effects of fulvestrant 750 mg in premenopausal women with estrogen-receptor-positive primary breast cancer. Eur J Cancer 2008;44: 391-399
151. McKeage K, Curran MP, Plosker GL. Fulvestrant: A review of its use in hormone receptorpositive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Drugs 2004;64: 633-648 (Pubitemid 38482444)
152. Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: A multinational, doubleblind, randomized trial. J Clin Oncol 2004; 22:1605-1613
153. Verhoeven MO, Teerlink T, Kenemans P, Vogelvang TE, van der Mooren MJ. Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator: A 12-week, randomized, placebocontrolled, double-blind, dose-ranging study in healthy postmenopausal women. Menopause 2007;14:235-242
154. Vogelvang TE, Mijatovic V, Kenemans P, Emeis JJ, Heijst JA, van der Mooren MJ. The effects of 12 weeks of HMR 3339, a novel selective estrogen receptor modulator, on markers of coagulation and fibrinolysis: A randomized, placebo-controlled, double-blind, doseranging study in healthy postmenopausal women. Am J Obstet Gynecol 2005;193:1384-1394 (Pubitemid 41395109)
155. Vogelvang TE, Leurs JR, Mijatovic V, Willemse J, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces concentrations of procarboxypeptidase U, an inhibitor of fibrinolysis. A randomized, placebo-controlled study in postmenopausal women. J Thromb Haemost 2005;3:1090-1092 (Pubitemid 41632844)
156. Vogelvang TE, Mijatovic V, Kenemans P, Teerlink T, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women. Fertil Steril 2004;82: 1540-1549 (Pubitemid 39611380)
157. Vogelvang TE, Mijatovic V, Kenemans P, Schalkwijk CG, van der Mooren MJ. Effect of HMR 3339, a novel selective estrogen receptor modulator, on C-reactive protein levels in healthy postmenopausal women. Am J Cardiol 2004;94:1205-1208
158. Ammann P, Bourrin S, Brunner F, et al. A new selective estrogen receptor modulator HMR- 3339 fully corrects bone alterations induced by ovariectomy in adult rats. Bone 2004;35: 153-161
159. Yoles I, Yogev Y, Frenkel Y, Hirsch M, Nahum R, Kaplan B. Efficacy and safety of standard versus low-dose Femarelle (DT56a) for the treatment of menopausal symptoms. Clin Exp Obstet Gynecol 2004;31:123-126
160. Yoles I, Yogev Y, Frenkel Y, Nahum R, Hirsch M, Kaplan B. Tofupill/Femarelle (DT56a): A new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss. Menopause 2003;10:522-525
161. Somjen D, Yoles I. DT56a (Tofupill/Femarelle) selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the
162. Coelingh Bennink HJT, Holinka CF, Dicfaluzy E. Estetrol review: profile and potential clinical applications. Climacteric 2008;11(Suppl 1):47-58
163. Coelingh Bennink HJT, Heegaard A-M, Visser M, Holinka CF, Christiansen C. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric 2008;11(Suppl 1):2-14
164. Holinka CF, Brincat M, Coelingh Bennink HJT. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric 2008;11(Suppl 1):15-21
165. Coelingh Bennink HJT, Singer C, Simoncini T, Genazzani AR, Holinka CF, Kubista E. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric 2008; 11(Suppl 1):29
166. Coelingh Bennink HJT, Skouby S, Bouchard P, Holinka CF. Ovulation inhibition by estetrol in an in vivo model. Contraception 2008;77: 186-190
167. Shibutani S, Ravindernath A, Terashima I, Suzuki N, Laxmi YR, Kanno Y. Mechanism of lower genotoxicity of toremifene compared with tamoxifen. Cancer Res 2001;61:3925-3931
168. Hachisuga T, Tsujioka H, Horiuchi S, Udou T, Emoto M, Kawarabayashi T. K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene. Br J Cancer 2005;92: 1098-1103
169. Addo S, Yates RA, Laight A. A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer 2002;87:1354-1359