What can be learned from the levormeloxifene experience?

Acta Obstetricia et Gynecologica Scandinavica

Volumn 85, Issue 2, 2006, Pages 135-142

  Ravn, Pernille ^a,b   Nielsen, Therese ^a   Christiansen, Claus ^a  

^a CENTER FOR CLINICAL AND BASIC RESEARCH   (Denmark)

^b ODENSE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Levormeloxifene; Postmenopausal osteoporosis; SERM

Indexed keywords

ARZOXIFENE; BASEDOXIFENE; CENTCHROMAN; DROLOXIFENE; ESTRADIOL; IDOXIFENE; MIPROXIFENE PHOSPHATE; NORETHISTERONE ACETATE; OSPEMIFENE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; TOREMIFENE; UNCLASSIFIED DRUG; PYRROLIDINE DERIVATIVE;

ABDOMINAL PAIN; BLEEDING; BONE DENSITY; BONE TURNOVER; BREAST CANCER; CLINICAL TRIAL; CONSTIPATION; DRUG EFFICACY; DRUG TOLERABILITY; EDEMA; ENDOMETRIAL DISEASE; ENDOMETRIUM HYPERPLASIA; ENDOMETRIUM POLYP; GYNECOLOGIC DISEASE; HORMONE SUBSTITUTION; HOT FLUSH; HUMAN; LEG CRAMP; LEUKORRHEA; MASTALGIA; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; OVARIECTOMY; POLYP; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; STATISTICAL SIGNIFICANCE; URINARY FREQUENCY; URINARY TRACT DISEASE; URINE INCONTINENCE; UTERINE CERVIX DISEASE; UTERUS PROLAPSE; VAGINA BLEEDING; VAGINAL DISCOMFORT; VASCULARIZATION; VERTEBRA; ANIMAL; DRUG EFFECT; FEMALE; POSTMENOPAUSE OSTEOPOROSIS;

ANIMALS; BONE DENSITY; CLINICAL TRIALS; FEMALE; HUMANS; OSTEOPOROSIS, POSTMENOPAUSAL; PYRROLIDINES; SELECTIVE ESTROGEN RECEPTOR MODULATORS;

EID: 33645637712     PISSN: 00016349     EISSN: 16000412     Source Type: Journal    
DOI: 10.1080/00016340500345691     Document Type: Review

References (44)

1. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux A, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med. 1997;337(23):1641-7.
2. 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(2):233-41.
3. Buzdar A, Hayes D, El-Khoudary A, Yan S, Lonning P, Lichinitser M et al.; Droloxifene 301 Study Group. Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. Breast Cancer Res Treat 2002; 73(2): 161-75.
4. Hendrix SL, McNeeley G. Effect of selective estrogen receptor modulators on reproductive tissues other than endometrium. Ann NY Acad Sci. 2001;949:243-50.
5. Cuzick J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003;361(9354):296-300.
6. Mitlak BH, Cohen FJ. Selective estrogen receptor modulators: a look ahead. Drugs. 1999;57(5):653-63.
7. Singh MM. Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders. Med Res Rev. 2001;21(4):302-47.
8. Misra NC, Nigam PK, Gupta R, Argarwal AK, Kamboj VP. Centchroman - a non-steroidal anti-cancer agent for advanced breast cancer: phase-II study. Int J Cancer. 1989;43(5):781-3.
9. Investigators Brochure. Levormeloxifene (NNC 46-0020), sixth edition. Denmark: Novo Nordisk; 1998.
10. Hotchkiss CE, Stavisky R, Nowak J, Brommage R, Lees CJ. Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys. Bone. 2001;29(1):7-15.
11. Holm P, Shalmi M, Korsgaard N, Guldhammer B, Skouby SO, Stender S. A partial estrogen receptor agonist with strong antiatherogenic properties without noticeable effect on reproductive tissue in cholesterol-fed female and male rabbits. Arterioscler Thromb Vasc Biol. 1997;17(10):2264-72.
12. Skrumsager BK, Kiehr B, Pedersen PC, Gerrits M, Watson N, Bjarnason K. Levormeloxifene: safety, pharmacodynamics and pharmacokinetics in healthy postmenopausal women following single and multiple doses of a new selective oestrogen receptor modulator. J Clin Pharmacol. 2002;53(3):284-95.
13. Alexandersen P, Riis BJ, Stakkestad JA, Delmas PD, Christiansen C. Efficacy of levormeloxifene in the prevention of postmenopausal bone loss and on the lipid profile compared to low dose hormone replacement therapy. J Clin Endocrinol Metab. 2001;2(86):755-60.
14. Warming L, Christoffersen C, Riis BJ, Stakkestad JA, Delmas PD, Christiansen C. Adverse effects of a SERM (Levormeloxifene). Safety parameters and bone mineral density 12 months after treatment withdrawal. Maturitas. 2003;44:189-99.
15. Bain S, Shalmi M, Korsgaard N. Levormeloxifene, a non-steroidal estrogen receptor therapeutic, prevents bone loss, reduces serum cholesterol, and has differentiated uterine effects in the ovariectomized rat. Abstract. Maturitas. 1997;27:144.
16. Goodrich JA, Clarkson TB, Cline JM, Jenkins AJ, Del Signore MJ. Value of the micropig model of menopause in the assessment of benefits and risks of postmenopausal therapies for the cardiovascular and reproductive tissues. Fertil Steril. 2003;79(Suppl 1):779-88.
17. Goldstein S, Nanavati N. Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol. 2002;187(3):521-7.
18. Osborne CK, Zhao H, Fuqua SAW. Selective estrogen receptor modulators: structure, function, and clinical use. J Clin Oncol. 2000;18(17):3172-86.
19. Murphy LJ, Murphy LC, Friesen HG. Estrogen induces insulin-like growth factor-I expression in the rat uterus. Mol Endocrinol. 1987;1(7):445-50.
20. Norstedt G, Levinovitz A, Eriksson H. Regulation of uterine insulin-like growth factor I mRNA and insulin-like growth factor II mRNA by estrogen in the rat. Acta Endocrinol (Copenh). 1989;120(4):466-72.
21. Mukku VR, Stancel GM. Regulation of epidermal growth factor receptor by estrogen. J Biol Chem. 1985;260(17):9820-4.
22. Stygar D, Muravitskaya N, Eriksson B, Eriksson H, Sahlin L. Effects of SERM (selective estrogen receptor modulator) treatment on growth and proliferation in the rat uterus. Reprod Biol Endocrinol. 2003;1(1):4026.
23. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators-mechanisms of action and application to clinical practice. N Engl J Med. 2003;348(7):618-29.
24. Shang Y, Brown M. Molecular determinants for the tissue specificity of SERMs. Science. 2002;295(5564):2465-8.
25. 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(6):1007-14.
26. McMeekin DS, Gordon A, Fowler J, Melemed A, Buller R, Burke T, et al. A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer. Gynecol Oncol. 2003;90(1):64-9.
27. Ma YL, Bryant HU, Zeng Q, Palkowitz A, Jee WS, Turner CH, Sato M. Long-term dosing of arzoxifene lowers cholesterol, reduces bone turnover, and preserves bone quality in ovariectomized rats. J Bone Miner Res. 2002;17(12):2256-64.
28. 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.
29. Ronkin S, Northington R, Baracat E, Nunes MG, Archer DF, Constantine G, Pickar JH. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol. 2005;105(6):1397-404.
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(9):3999-4008.
31. DeGregorio MW, Wurz GT, Taras TL, Erkkola RU, Halonen KH, Huupponen RK. Pharmacokinetics of (deaminohydroxy)toremifene in humans: a new, selective estrogen-receptor modulator. Eur J Clin Pharmacol. 2000;56(6-7):469-75.
32. 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(5):433-9.
33. 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(3):152-8.
34. Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke AC. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet. 1976;1(7968):1038-41.
35. Erberich LC, Alcantara VM, Picheth G, Scartezini M. Hormone replacement therapy in postmenopausal women and its effects on plasma lipids levels. Clin Chem Lab Med. 2002;40(5):446-51.
36. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy (HERS II). J Am Med Assoc. 2002;288:49-57.
37. Writing Group for the Women's Health Initiative Investigators. Risk and benefits of estrogen plus progestin in healthy postmenopausal women. J Am Med Assoc. 2002;288:321-33.
38. Bloch-Thomsen A, Silvestri S, Christiansen C, Bjarnason NH. Associated response in bone mineral density and atherogenic lipid profile during treatment with two different selective estrogen receptor modulators: levormeloxifene and raloxifene. Climacteric. 2003;6(2):159-67.
39. Kiehr B, Skrumsager BK, Müller M, Pedersen PC. Pharmacokinetics of levormeloxifene in young versus elderly postmenopausal women. Clin Ther. 2001;23(1):62-71.
40. Mountfield RJ, Kiehr B, John BA. Metabolism, disposition, excretion, and pharmacokinetics of levormeloxifene, a selective estrogen receptor modulator, in the rat. Drug Metab Dispos. 2000;28(5):503-13.
41. Mountfield RJ, Panduro AM, Wassmann O, Thompson M, John B, van der Merbel N. Metabolism of levormeloxifene, a selective oestrogen receptor modulator, in the Sprague-Dawley rat, Cynomolgus monkey and postmenopausal woman. Xenobiotica. 2000;30(2):201-17.
42. Neven P. The Effect of Tamoxifen on the Uterus in Postmenopausal Breast Cancer Patients. Leuven, Belgium: Leuven University Press; 1998.
43. Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J et al. for the Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal Osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal Osteoporosis. Endocr Rev 2002; 23(4): 524-8.
44. Tiitinen A, Nikander E, Hietanen P, Metsa-Heikkila M, Ylikorkala O. Changes in bone mineral density during and after 3 years' use of tamoxifen or toremifene. Maturitas. 2004;48(3):321-7.