Tissue selective estrogen complex combinations with bazedoxifene/conjugated estrogens as a model

Climacteric

Volumn 16, Issue 6, 2013, Pages 618-628

  Pinkerton, J V ^a   Komm, B S ^b   Mirkin, S ^b  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

^b PFIZER INC   (United States)

Author keywords

Bazedoxifene; BZA CE; Conjugated Estrogens; Menopausal Symptoms; Menopause; Safety; Tissue Selective Estrogen Complex; TSEC

Indexed keywords

BAZEDOXIFENE; CARBOXY TERMINAL TELOPEPTIDE; CONJUGATED ESTROGEN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; GESTAGEN; HOX 10 PROTEIN; HOX PROTEIN; LASOFOXIFENE; OSTEOCALCIN; PLACEBO; PROGESTERONE RECEPTOR; RALOXIFENE; TRANSCRIPTION FACTOR EMX2; UNCLASSIFIED DRUG;

AMENORRHEA; BONE DENSITY; CARDIOVASCULAR DISEASE; CELL CULTURE; CELL DIFFERENTIATION; CELL PROLIFERATION; CHOLESTEROL BLOOD LEVEL; CLIMACTERIUM; DRUG EFFICACY; DRUG SAFETY; ENDOMETRIAL THICKNESS; ENDOMETRIUM; ENDOMETRIUM CELL; ENDOMETRIUM HYPERPLASIA; ENDOMETRIUM POLYP; ESTROGEN ACTIVITY; GENE EXPRESSION; HORMONAL THERAPY; HOT FLUSH; HUMAN; MAMMARY GLAND; MASTALGIA; MENOPAUSAL SYNDROME; MONOTHERAPY; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; PATIENT SATISFACTION; PH; POSTMENOPAUSE; PRIORITY JOURNAL; PROTEIN DEGRADATION; QUALITY OF LIFE; REVIEW; SIDE EFFECT; UTERUS WEIGHT; VASOMOTOR REFLEX; VEIN THROMBOSIS;

ANIMALS; ATROPHY; ESTROGENS, CONJUGATED (USP); FEMALE; GENE EXPRESSION; HOT FLASHES; HUMANS; INDOLES; LIPID METABOLISM; OSTEOPOROSIS, POSTMENOPAUSAL; QUALITY OF LIFE; SELECTIVE ESTROGEN RECEPTOR MODULATORS; SLEEP; VAGINA; VENOUS THROMBOEMBOLISM; VULVA;

EID: 84887446224     PISSN: 13697137     EISSN: 14730804     Source Type: Journal    
DOI: 10.3109/13697137.2013.810437     Document Type: Review

References (76)

1. Burger H G, Hale G E, Robertson D M, Dennerstein L. A review of hormonal changes during the menopausal transition: Focus on fi ndings from the Melbourne Women's Midlife Health Project. Hum Reprod Update 2007;13:559-65
2. Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: Study of Women's Health Across the Nation. Am J Public Health 2006;96:1226-35
3. Levine KB, Williams RE, Hartmann KE. Vulvovaginal atrophy is strongly associated with female sexual dysfunction among sexually active postmenopausal women. Menopause 2008;15:661-6
4. North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257-71
5. 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;326:852-6
6. Powles TJ, Hickish T, Kanis J A, Tidy A, Ashley S. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. J Clin Oncol 1996;14:78-84
7. Delmas P D, Bjarnason N H, Mitlak B H, et a l. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-7
8. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637-45
9. Maximov P Y, Lee T M, Jordan V C. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol 2012;8:135-55
10. Portman D J, Bachmann G A, Simon J A. O spemifene, anovel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013 Jan 28. Epub ahead of print
11. Simon J A, Lin V H, Radovich C, Bachmann G A. O ne-year longterm safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause 2012 Nov 8. Epub ahead of print
12. Shionogi Inc. Shionogi Receives FDA Approval For Osphena □ (Ospemifene) For The Treatment Of Dyspareunia, ASymptom Of Vulvar And Vaginal Atrophy (VVA), Due To Menopause. http://www.prnewswire.com/news-releases-Test/ shionogireceives-fda-Approval-for-osphena-ospemifene-for-The-Treatmentof- dyspareunia-A-symptom-of-vulvar-And-vaginal-Atrophyvva-due-To-menopause- 193358451.html [serial online]; Accessed May 7, 2013
13. Archer DF. Tissue-selective estrogen complexes: A promising option for the comprehensive management of menopausal symptoms. Drugs Aging 2010;27:533-44
14. Cummings SR, Ensrud K, Delmas PD, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 2010;362:686-96
15. Kendler DL, Palacios S, Cox DA, et al. Arzoxifene versus raloxifene: Effect on bone and safety parameters in postmenopausal women with osteoporosis. Osteoporos Int 2012;23:1091-101
16. Cummings S R, McClung M, Reginster J Y, et a l. A rzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res 2011;26:397-404
17. Silverman S L, Christiansen C, Genant H K, et a l. E ffi cacy 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
18. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: A comprehensive review. Health Qual Life Outcomes 2005;3:47
19. Ayers B, Hunter MS. Health-related quality of life of women with menopausal hot fl ushes and night sweats. Climacteric 2013;16:235-9
20. K ulak J, Jr., F erriani RA, Komm BS, Taylor HS. Tissue selective estrogen complexes (TSECs) differentially modulate markers of proliferation and differentiation in endometrial cells. Reprod Sci 2013;20:129-37
21. 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
22. Oliva P, Roncoroni C, Radaelli E, et a l. G lobal profi ling of TSEC proliferative potential by the use of a reporter mouse for proliferation. Reprod Sci 2013;20:119-28
23. Ethun K F, Wood C E, Cline J M, Register T C, Appt S E, Clarkson TB. Endometrial profi le of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model. Menopause 2013 Feb. Epub ahead of print
24. Berrodin T J, Chang K C, Komm B S, Freedman L P, Nagpal S. Differential biochemical and cellular actions of Premarin estrogens: Distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol 2009;23:75-85
25. Lewis-Wambi J S, Kim H, Curpan R, Grigg R, Sarker M A, Jordan VC. The selective estrogen receptor modulator bazedoxifene inhibits hormone-independent breast cancer cell growth and down-regulates estrogen receptor alpha and cyclin D1. Mol Pharmacol 2011;80:610-20
26. Chang K CN, Wang Y, Bodine P V, Nagpal S, Komm B S. G ene expression profi ling studies of three SERMs and their conjugated estrogen combinations in human breast cancer cells: Insights into the unique antagonistic effects of bazedoxifene on conjugated estrogens. J Steroid Biochem Mol Biol 2010;118:117-24
27. Song Y, Santen RJ, Wang JP, Yue W. Effects of the conjugated equine estrogen/ bazedoxifene tissue-selective estrogen complex (TSEC) on mammary gland and breast cancer in mice. Endocrinology 2012;153:5706-15
28. Ethun K F, Wood C E, Register T C, Cline J M, Appt S E, Clarkson TB. Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. Menopause 2012;19:1242-52
29. Kharode Y, Bodine P V, 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;149:6084-91
30. Dey M, Lyttle CR, Pickar JH. Recent insights into the varying activity of estrogens. Maturitas 2000;34(Suppl 2):S25-33
31. Campagnoli C, Ambroggio S, Biglia N, Sismondi P. C onjugated estrogens and breast cancer risk. Gynecol Endocrinol 1999;13(Suppl 6):13-19
32. Utian W H, Shoupe D, Bachmann G, Pinkerton J V, Pickar J H. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;75:1065-79
33. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002;287:2668-76
34. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH. Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women. Osteoporos Int 2005;16:372-9
35. Bergkvist L, Adami H O, Persson I, Hoover R, Schairer C. The risk of breast cancer after estrogen and estrogen-progestin replacement. N Engl J Med 1989;321:293-7
36. Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295:1647-57
37. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: Extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet Oncol 2012;13:476-86
38. LaCroix AZ, Chlebowski RT, Manson JE, et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: A randomized controlled trial. JAMA 2011;305:1305-14
39. Kagan R. The tissue selective estrogen complex: A novel approach to the treatment of menopausal symptoms. J Womens Health (Larchmt) 2012;21:975-81
40. Stovall DW, Utian WH, Gass ML, et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause 2007;14:510-17
41. Davis SR, O'Neill SM, Eden J, et al. Transition from estrogen therapy to raloxifene in postmenopausal women: Effects on treatment satisfaction and the endometrium-A pilot study. Menopause 2004;11:167-75
42. Carranza-Lira S, Gooch AL, Saldivar N, Osterwalder MS. Climacteric symptom control after the addition of low-dose esterifi ed conjugated estrogens to raloxifene standard doses. Int J Fertil Womens Med 2007;52:93-6
43. 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
44. 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
45. Lobo R A, Pinkerton J V, Gass M L, et a l. Evaluation of bazedoxifene/ conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profi le. Fertil Steril 2009;92:1025-38
46. Pickar JH, Yeh I-T, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/ conjugated estrogens as a menopausal therapy. Fertil Steril 2009;92:1018-24
47. Harvey J A, Holm M K, Ranganath R, Guse P A, Trott E A, Helzner E. The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis. Menopause 2009;16:1193-6
48. Food and Drug Administration. Guidance for Industry. Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms-Recommendations for Clinical Evaluation, 2003
49. Mirkin S, Taylor H S, Archer D F, Pickar J H, Thompson J, Komm BS. Differential effects of bazedoxifene/conjugated estrogens and hormone therapy on the endometrium. Menopause 2012;19:1374
50. Komm B S, Mirkin S. The tissue selective estrogen complex: A promising new menopausal therapy. Pharmaceuticals 2012;5:899-924
51. 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
52. Utian W, Yu H, Bobula J, Mirkin S, Olivier S, Pickar JH. Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women. Maturitas 2009;63:329-35
53. 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
54. Bachmann G, Bobula J, Mirkin S. Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy. Climacteric 2010;13:132-40
55. Pinkerton JV, Harvey J A, Pan K, et al. Breast effects of bazedoxifene-conjugated estrogens: A randomized controlled trial. Obstet Gynecol 2013;121:959-68
56. Mirki S, Komm B S, Pan K, Chines A A. Effects of bazedoxifene/ conjugated estrogens on endometrial safety and bone in postmenopausal women. Climacteric 2013;16:338-46
57. Yu H, Racketa J, Chines A A, Mirkin S. H ot fl ush symptom-free days with bazedoxifene/conjugated estrogens in postmenopausal women. Climacteric 2013;16:252-7
58. Mac Bride MB, Rhodes D J, Shuster L T. V ulvovaginal atrophy. Mayo Clin Proc 2010;85:87-94
59. Pinkerton J V, Chines A A, Racketa J, Mirkin S. B azedoxifene/ conjugated estrogens (BZA/CE): Effect on sleep parameters in postmenopausal women. Menopause 2010;17:1237-8
60. Lewis JE, Hilditch JR, Wong CJ. F urther psychometric property development of the Menopause-Specifi c Quality of Life questionnaire and development of a modifi ed version, MENQOL-Intervention questionnaire. Maturitas 2005;50:209-21
61. Hill C D, Fehnel S E, Bobula J D, Y u H, McLeod L D. D evelopment and preliminary validation of the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ). Menopause 2007;14:1047-55
62. National Osteoporosis Foundation. Clinician's guide to prevention and treatment of osteoporosis. http://www.nof.org/professionals/ pdfs/NOF-ClinicianGuide2009-v7.pdf [serial online]; Accessed July 23, 2010
63. Siris E S, Miller P D, Barrett-Connor E, et a l. I dentifi cation and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA 2001;286:2815-22
64. Gallagher J C, Lindsay R, Pan K, Mirkin S, Chines A. Effects of bazedoxifene/conjugated estrogens on bone mineral density and bone turnover markers in postmenopausal women: A doubleblind, randomized, placebo-And active-controlled phase 3 study. J Bone Miner Res 2011;26(Suppl 1):S46
65. Lejskova M, Alusik S, Valenta Z, Adamkova S, Pitha J. N atural postmenopause is associated with an increase in combined cardiovascular risk factors. Physiol Res 2012;61:587-96
66. Rossouw J E, Cushman M, Greenland P, et a l. I nfl ammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the Women's Health Initiative trials of hormone therapy. Arch Intern Med 2008;168:2245-53
67. Pearson TA, Mensah GA, Hong Y, Smith SC, Jr. CDC/AHA workshop on markers of infl ammation and cardiovascular disease: Application to clinical and public health practice: Overview. Circulation 2004;110:e543-e544
68. Wardell SE, Kazmin D, McDonnell DP. Research resource: Transcriptional profi ling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes. Mol Endocrinol 2012;26:1235-48
69. Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease: The Women's Health Initiative. Arch Intern Med 2006;166:357-65
70. Lethaby A, Suckling J, Barlow D, Farquhar CM, Jepson R G, Roberts H. Hormone replacement therapy in postmenopausal women: Endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004;CD000402
71. Archer DF. Endometrial bleeding in postmenopausal women: With and without hormone therapy. Menopause 2011;18 : 416-20
72. Archer D F, Pickar J H, Bottiglioni F. B leeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group. Obstet Gynecol 1994;83:686-92
73. Harvey J A, Pinkerton J V, Baracat E C, Shi H, Chines A A, Mirkin S. Breast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens. Menopause 2013;20:138-45
74. Kulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, aselective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 2011;152:3226-32
75. Archer DF, Lobo RA, Pan K, et al. Safety and tolerability of bazedoxifene/conjugated estrogens in postmenopausal women: Fi ndings from a 1-year, randomized, placebo-And active-controlled, phase 3 trial. Menopause 2011;18:1355-6
76. Pinkerton JV, Pan K, Abraham L, Racketa J, Chines AA, Mirkin S. Effects of bazedoxifene/conjugated estrogens on sleep parameters and health-related quality of life in postmenopausal women. Menopause 2011;18:1346