222
Views
16
CrossRef citations to date
0
Altmetric
Review

Pharmacology and clinical applications of selective estrogen receptor modulators

&
Pages 188-205 | Received 26 Nov 2008, Accepted 01 Dec 2008, Published online: 03 Jul 2009

References

  • Riggs B L, Hartmann L C. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med 2003; 348: 618–629
  • Rossouw J W, Anderson G L, Prentice R L, 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
  • Smith C L, O'Malley B W. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev 2004; 5: 45–71
  • Meegan M J, Lloyd D G. Advances in the science of estrogen receptor modulation. Curr Med Chem 2003; 10: 181–210
  • Bryant H. Selective estrogen receptor modulators. Rev Endocr Metab Dis 2002; 3: 231–241
  • Patankar S S, Kaore S B, Sawane M V, Mishra N V, Deshkar A M. Effect of clomiphene citrate on sperm density in male partners of infertile couples. Ind J Physiol Pharmacol 2007; 51: 195–198
  • Uyar Y, Koltan S O, Pögün S, Vatansever S, Caglar H. The effect of clomiphene citrate on osteoporosis in ovariectomized rats. Arch Gynecol Obstet 2008; 278: 107–114
  • Rozen T D, Saper J R, Sheftell F D, Dodick D W. Clomiphene citrate as a new treatment for SUNCT: hormonal manipulation for hypothalamic-influenced trigeminal autonomic cephalalgias. Headache 2005; 45: 754–756
  • Rozen T. Clomiphene citrate for treatment refractory chronic cluster headache. Headache 2008; 48: 286–290
  • Asch R H, Greenblatt R B. Update on the safety and efficacy of clomiphene citrate as a therapeutic agent. J Reprod Med 1976; 17: 175–180
  • Adashi E Y. Clomiphene citrate: the case for a monoisometric preparation. Baillieres Clin Obstet Gynaecol 1993; 7: 331–347
  • Derman S G, Adashi E Y. Adverse effects of fertility drugs. Drug Safety 1994; 11: 408–421
  • Legro R S, Barnhart H X, Schlaff W D. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356: 551–566
  • Osborn C K. Drug therapy: tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339: 1609–1618
  • Buckley M M, Goa K L. Tamoxifen: a reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic uses. Drugs 1989; 37: 451–490
  • Langhey Fahey SM, Jordan V C, Fritz N F, Robinson S P, Waters D, Tormey D C. Clinical pharmacology and endocrinology of long term tamoxifen therapy. Long Term Tamoxifen Treatment for Breast Cancer, Jordan VC. University of Wisconsin Press, Madinson 1994; 27–56
  • Lein E A, Solheim E, Ueland P M. Distribution of tamoxifen and its metabolites in rat and human tissues during steady state treatment. Cancer Research 1991; 51: 4837–4844
  • Osborne C K, Elledge R M, Fuqua S AW. Estrogen receptors in breast cancer therapy. Sci Med 1996; 3: 32–41
  • Arteaga C L, Osborne C K. Growth factors as mediators of estrogen/antiestrogen action in human breast cancer cells. Regulatory Mechanisms in Breast Cancer: Advances in Cellular and Molecular Biology of Breast Cancer, Lippman ME, Dickson RB. Kluwer Academic, Boston 1991; 289–304
  • The Early Breast Cancer Trialists Collaborative Group. Tamoxifen for early breast cancer: an overview of randomized trials. Lancet 1998; 351: 1451–1467
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Rivkin S E, 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
  • Pritchard K I, Paterson A H, 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
  • 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: 1005–1118
  • Saez R A, Osborne C K. Hormonal treatment of advanced breast cancer. Current Clinical Oncology, Vol. 1 Breast Cancer, Kennedy BJ. Alan R. Liss, New York 1989; 163–172
  • Catherino W H, Jordan V C. A risk benefit assessment of tamoxifen therapy. Drug Saf 1993; 8: 381–397
  • Castrellon A B, Glück S. Chemoprevention of breast cancer. Expert Rev Anti Cancer Ther 2008; 8: 443–452
  • Fisher B, Constantino J P, Wickerham D L, 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
  • Derman O, Kanbur N O, Kutluk T. Tamoxifen treatment for pubertal gynecomastia. Int J Adolesc Med Health 2003; 15: 359–363
  • Hanavadi S, Banerjee D, Monypenny I J, Mansel R E. The role of tamoxifen in the management of gynaecomastia. Breast 2006; 15: 276–280
  • Khan H N, Rampaul R, Blamey R W. Management of physiological gynecomastia with tamoxifen. Breast 2004; 13: 61–65
  • Devoto C E, Madariaga A M, Lioi C X, Mardones N. Influence of size and duration of gynecomastia on its response to treatment with tamoxifen. Revista Medica de’ Chile 2007; 135: 1558–1565
  • Parker L N, Gray D R, Lai M K, Levin E R. Treatment of gynecomastia with tamoxifen: a double-blind crossover study. Metabolism 1986; 35: 705–708
  • Li C P, Lee F Y, Hwang S J, et al. Treatment of mastalgia with tamoxifen in male patients with liver cirrhosis: a randomized crossover study. Am J Gastroenterol 2000; 95: 1051–1055
  • Love R R, Mazess R B, Barden H S, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N Engl J Med 1992; 326: 852–856
  • Williams J K, Wagner J D, Li Z, Golden D L, Adams M R. Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. Arterioscler Thromb Vasc Biol 1997; 17: 403–408
  • Waltman N L, Ott C D, Twiss J J, Gross G J, Lindsey A M, Moore T E. Bone mineral density and bone turnover in postmenopausal women treated for breast cancer. Cancer Nursing 2008; 31: 182–190
  • 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
  • Kristensen B, Ejlertsen B, Mouridsen H T, Andersen K W, Lauritzen J B. Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen. Breast Cancer Res Treat 1996; 39: 321–326
  • 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
  • Rutqvist L E, 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
  • Bilimoria M M, Jordan V C, Morrow M. Additional benefits of tamoxifen for post-menopausal patients. Tamoxifen: A Guide for Clinicians and Patients, Jordon VC. PRR, Inc, Huntington, NY 1996; 75–89
  • Ek R O, 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
  • Gielen S C, Santegoets L A, Hanifi-Moghaddam P, Burger C W, Blok L J. Signaling by estrogens and tamoxifen in the human endometrium. J Steroid Biochem Mol Biol 2008; 109: 219–223
  • Gorodeski G I, 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
  • Stewart H J, Prescott R J, Forrest A P. Scottish Adjuvant Tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst 2001; 93: 456–462
  • Erdemoglu E, Güney M, Keskin B, Mungan T. Tamoxifen and giant endometrial polyp. Eur J Gynecol Oncol 2008; 29: 198–199
  • Dede M, Gezginç K, 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
  • 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
  • Chandanos E, Lindblad M, Rubio C A, et al. Tamoxifen exposure in relation to gastric adenocarcinoma development. Eur J Cancer 2008; 44: 1007–1014
  • 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-receptor-positive tumors. N Engl J Med 1989; 320: 479–484
  • 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
  • Bao T, Davidson N E. Adjuvant endocrine therapy for premenopausal women with early breast cancer. Breast Cancer Res 2007; 9: 115
  • Love R R, Cameron L, Connell B L, Leventhal H. Symptoms associated with tamoxifen treatment in post menopausal women. Arch Intern Med 1991; 151: 1842–1847
  • Saphner T, Tormey D C, Gray R. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. J Clin Oncol 1991; 9: 286–294
  • McDonald C C, Alexander F E, Whyte B W, Forrest A P, Stewart H J. 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
  • Vogel V G, Constantino J P, Wickerham D L, 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
  • Nayfield S G, Gorin M B. Tamoxifen-associated eye disease: a review. J Clin Oncol 1996; 14: 1018–1026
  • Gorin M B, Day R, Costantino J P, et al. Long term tamoxifen citrate use and potential ocular toxicity. Am J Ophthalmol 1998; 125: 493–501
  • Varas-Lorenzo C, Garcia-Rodriguez L A, Cattaruzzi C, Troncon M G, 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
  • Yao J C, Thomakos N, McLaughlin P, Buchholz T A, Kudelka A P. Tamoxifen-induced thrombocytopenia. Am J Clin Oncol 1999; 22: 529–532
  • Nasiroğlu N, Pamukçuoğlu M, Abali H, Oksüzoğlu B, Uner A, Zengin N. Tamoxifen induced-thrombocytopenia: it does occur. Med Oncol 2007; 24: 453–454
  • Buzdar A U, Hortobagyi G N. Tamoxifen and toremifene in breast cancer: comparison of safety and efficacy. J Clin Oncol 1998; 26: 348–353
  • Hayes D F, Van Zyl J A, 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
  • Lewis-Wambi J S, Jordan V C. Treatment of postmenopausal breast cancer with selective estrogen receptor modulators (SERMs). Breast Dis 2005–2006; 24: 93–105
  • Dodwell D, Wardley A, Johnston S. Postmenopausal advanced breast cancer: options for therapy after tamoxifen and aromatase inhibitors. Breast 2006; 15: 584–594
  • 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
  • Smith M R, Malkowicz S B, 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
  • 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
  • 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 pre- and post-menopausal women. Breast Cancer Res Treat 2005; 93: 277–287
  • Raghow S, Hooshdaran M Z, Katiyar S, Steiner M S. Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model. Cancer Res 2002; 62: 1370–1376
  • 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
  • Smith M R, Malkowicz S B, 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
  • Marttunen M B, 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
  • 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
  • O'Regan R M, Cisneros G M, England G M, et al. Effects of the antiestrogens tamoxifene, toremifene and ICI 182,780 on endometrial cancer growth. J Natl Cancer Inst 1998; 90: 1552–1555
  • Shapiro C L, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med 2001; 344: 1997–2008
  • Harvey H A, Kimura M, Hajba A. Toremifene: an evaluation of its safety profile. Breast 2006; 15: 142–157
  • 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
  • Maenpaa J U, Ala-Fossi S L. Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. Drugs Aging 1997; 11: 261–270
  • Huang Y, Shen Y, Feng Y, Cao L, Leng Y. Anti-implantation effect of droloxifene in rats and its relationship with anti-estrogenic activity. Acta Pharmacol Sin 2005; 26: 1243–1247
  • Johnston S R. Endocrine manipulation in advanced breast cancer: recent advances with SERM therapies. Clin Cancer Res 2001; 7: 4376–4387
  • 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
  • Ke H Z, Crawford D T, 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
  • Ke H Z, Chen H K, Simmons H A. Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum cholesterol, and uterine histology in the ovariectomized rat model. Bone 1997; 20: 31–39
  • Herrington D M, Pusser B E, Riley W A, et al. Cardiovascular effects of droloxifene, a new selective estrogen receptor modulator, in healthy postmenopausal women. Arterioscler Thromb Vasc Biol 2000; 20: 1606–1612
  • Haarstad H, Lønning P E, Gundersen S, Wist E, Raabe N, Kvinnsland S. Influence of droloxifene on metastatic breast cancer as first-line endocrine treatment. Acta Oncol 1998; 37: 365–368
  • McCague R, Parr I B, Haynes B P. Metabolism of the 4-iodo derivative of tamoxifen by isolated rat hepatocytes: demonstration that the iodine atom reduces metabolic conversion and identification of four metabolites. Biochem Pharmacol 1990; 40: 2277–2283
  • Nuttall M E, Bradbeer J N, Stroup G B, 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
  • Johnston S R, Gumbrell L A, Evans T R. 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
  • Arpino G, Nair Krishnan M, Doval Dinesh C, Bardou V J, Clark G M, Elledge R M. Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer. Ann Oncol 2003; 14: 233–241
  • Fleischer A C, Wheeler J E, Yeh I T, 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
  • Albertazzi P, Sharma S. Urogenital effects of selective estrogen receptor modulators: a systematic review. Climacteric 2005; 8: 214–220
  • Komi J, Lankinen K S, 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
  • Komi J, Heikkinen J, Rutanen E M, 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
  • Voipio S K, Komi J, Kangas L, Halonen K, DeGregorio M W, Erkkola R U. Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas 2002; 43: 207–214
  • Rutanen E M, 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: 433–439
  • Wurz G T, Read K C, 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
  • Johnston C C, Jr, Bjarnason N H, Cohen F J, 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
  • Meunier P J, 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
  • Ettinger B, Black D M, Mitlak B H. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. JAMA 1999; 282: 637–645
  • 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
  • Ishani A, Blackwell T, Jamal S A, et al. MORE Investigators. The effect of raloxifene treatment in postmenopausal women with CKD. J Am Soc Nephrol 2008; 19: 1430–1438
  • Yaffe K, Krueger K, Cummings S R, 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
  • Lippman M E, Krueger K A, 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
  • Cauley J A, Norton L, Lippmann M E, 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
  • Martino S, Cauley J A, 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
  • 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
  • Vogel V G, Constantino J P, Wickerham D L, 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
  • Boss S M, Huster W J, Neild J A, Glant M D, Eisenhut C C, Draper M W. Effects of raloxifene hydrochloride on the endometrium of postmenopausal women. Am J Obstet Gynecol 1997; 177: 1458–1464
  • Delmas P D, Bjarnason N H, Mitlak B H, 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
  • 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
  • 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
  • Martino S, Disch D, Dowsett S A, Keech C A, Mershon J L. Safety assessment of raloxifene over eight years in a clinical trial setting. Curr Med Res Opin 2005; 21: 1441–1452
  • 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 65
  • Buzdar A, O'Shaughnessy J A, Booser D J, 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
  • Deshmane V, Krishnamurthy S, Melemed A S, Peterson P, Buzdar A U. Phase III double-blind trial of arzoxifene compared with tamoxifen for locally advanced or metastatic breast cancer. J Clin Oncol 2007; 25: 4967–4973
  • 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
  • Rendi M H, Suh N, Lamph W W, Krajewski S, Reed J C, Heyman R A. 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
  • 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
  • Ma Y L, Bryant H U, 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
  • Sato M, Turner C H, Wang T, Adrian M D, Rowley E, Bryant H U. LY353381.HCl: a novel raloxifene analog with improved SERM potency and efficacy in vivo. J Pharmacol Exp Ther 1998; 287: 1–7
  • Buzdar A, O'Shaughnessy J A, Booser D J, Pippen J E, Jr, Jones S E, Munster P N, 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
  • Gennari L. Lasofoxifene: a new type of selective estrogen receptor modulator for the treatment of osteoporosis. Drugs Today (Barc) 2006; 42: 355–367
  • Rosati R L, Da Silva Jardine P, Cameron K O, 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
  • Ke H Z, Paralkar V M, Grasser W A. 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
  • Gennari L. Lasofoxifene (Pfizer). Curr Opin Investig Drugs 2005; 6: 1067–1078
  • Ke H Z, Foley G L, Simmons H A, Shen V, Thompson D D. 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
  • Ke H Z, Qi H, Crawford D T, Chidshey-Frink K L, Simmons H A, Thompson D D. 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
  • Fountaine R, Nishizawa Y, Wei G, Dogolo L, Calcagni A, Gardner M J. Clinical pharmacology of lasofoxifene in Japanese and white postmenopausal women. J Clin Pharmacol 2006; 46: 693–699
  • Bramson C, Ouellet D, Roman D, Randinitis E, Gardner M J. A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment. J Clin Pharmacol 2006; 46: 29
  • 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
  • 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
  • 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
  • Portman D J, Moffett A H, Bachman G A, West C, Symons J. Lasofoxifene, a selective estrogen receptor modulator, improves objective measures of vaginal atrophy. Obstet Gynecol 2004; 103: 25–26
  • 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
  • Miller P D, Chines A A, Christiansen C, Hoeck H C, Kendler D L, Lewiecki E M. 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
  • Silverman S L, Christiansen C, Genant H K, 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
  • Kharode Y, Bodine P VN, Miller C P, Lyttle C R, Komm B S. 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
  • Nityanand S, . Clinical evaluation of centchroman: a new oral contraceptive. Hormone Antagonists for Fertility Regulation, Puri CP, Van Look PFA, et al. ISSRF, BombayIndia 1990
  • Dhar A, Srivastava A. Role of centchroman in regression of mastalgia and fibroadenoma. World J Surg 2007; 31: 1178–1184
  • Narayana Murthy P S, Sengupta S, Sharma S, Singh M M. 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
  • Labrie F, Champagne P, Labrie C, Roy J, Laverdière 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
  • 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
  • Young O E, Renshaw L, Macaskill E J, et al. Effects of fulvestrant 750 mg in premenopausal women with estrogen-receptor-positive primary breast cancer. Eur J Cancer 2008; 44: 391–399
  • McKeage K, Curran M P, Plosker G L. Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Drugs 2004; 64: 633–648
  • Howell A, Robertson J F, Abram P, Lichinitser M R, 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, double-blind, randomized trial. J Clin Oncol 2004; 22: 1605–1613
  • Verhoeven M O, Teerlink T, Kenemans P, Vogelvang T E, van der Mooren M J. Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator: a 12-week, randomized, placebo-controlled, double-blind, dose-ranging study in healthy postmenopausal women. Menopause 2007; 14: 235–242
  • Vogelvang T E, Mijatovic V, Kenemans P, Emeis J J, Heijst J A, van der Mooren M J. 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, dose-ranging study in healthy postmenopausal women. Am J Obstet Gynecol 2005; 193: 1384–1394
  • Vogelvang T E, Leurs J R, Mijatovic V, Willemse J, van der Mooren M J. 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
  • Vogelvang T E, Mijatovic V, Kenemans P, Teerlink T, van der Mooren M J. 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
  • Vogelvang T E, Mijatovic V, Kenemans P, Schalkwijk C G, van der Mooren M J. 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
  • 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
  • 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
  • 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
  • Somjen D, Yoles I. DT56a (Tofupill/Femarelle) selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus. J Steroid Biochem Mol Biol 2003; 86: 93–98
  • Coelingh Bennink H JT, Holinka C F, Dicfaluzy E. Estetrol review: profile and potential clinical applications. Climacteric 2008; 11(Suppl 1)47–58
  • Coelingh Bennink H JT, Heegaard A-M, Visser M, Holinka C F, Christiansen C. Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Climacteric 2008; 11(Suppl 1)2–14
  • Holinka C F, Brincat M, Coelingh Bennink H JT. Preventive effect of oral estetrol in a menopausal hot flush model. Climacteric 2008; 11(Suppl 1)15–21
  • Coelingh Bennink H JT, Singer C, Simoncini T, Genazzani A R, Holinka C F, Kubista E. Estetrol, a pregnancy-specific human steroid, prevents and suppresses mammary tumor growth in a rat model. Climacteric 2008; 11(Suppl 1)29
  • Coelingh Bennink H JT, Skouby S, Bouchard P, Holinka C F. Ovulation inhibition by estetrol in an in vivo model. Contraception 2008; 77: 186–190
  • Shibutani S, Ravindernath A, Terashima I, Suzuki N, Laxmi Y R, Kanno Y. Mechanism of lower genotoxicity of toremifene compared with tamoxifen. Cancer Res 2001; 61: 3925–3931
  • 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
  • Addo S, Yates R A, 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

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.