Differential effects of menopausal therapies on the endometrium

Menopause

Volumn 21, Issue 8, 2014, Pages 899-908

  Mirkin, Sebastian ^a   Archer, David F ^b   Taylor, Hugh S ^c   Pickar, James H ^d   Komm, Barry S ^a  

^a PFIZER INC   (United States)

^b EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Department of Medicine   (United States)

Author keywords

Bazedoxifene; Conjugated estrogens; Endometrial hyperplasia; Endometrium; Menopause; Selective estrogen receptor modulators

Indexed keywords

BAZEDOXIFENE; BAZEDOXIFENE PLUS CONJUGATED ESTROGEN; ESTROGEN; ESTROGEN RECEPTOR; GESTAGEN; LASOFOXIFENE; OSPEMIFENE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TAMOXIFEN; CONJUGATED ESTROGEN;

AMENORRHEA; BONE DENSITY; BONE DISEASE; CANCER RISK; CELL PROLIFERATION; DRUG SAFETY; DRUG TOLERABILITY; ENDOMETRIAL DISEASE; ENDOMETRIAL THICKNESS; ENDOMETRIUM; ENDOMETRIUM CANCER; ENDOMETRIUM CELL; ENDOMETRIUM HYPERPLASIA; ENDOMETRIUM POLYP; ESTROGEN ACTIVITY; ESTROGEN PROGESTIN THERAPY; ESTROGEN THERAPY; HORMONAL THERAPY; HUMAN; INCIDENCE; MENOPAUSAL SYNDROME; META ANALYSIS (TOPIC); NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSTMENOPAUSE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SPOTTING; UTERUS BLEEDING; VAGINA ATROPHY; VASOMOTOR DISORDER; DRUG EFFECTS; FEMALE; HOT FLASHES; MENOPAUSE;

ENDOMETRIUM; ESTROGEN REPLACEMENT THERAPY; ESTROGENS, CONJUGATED (USP); FEMALE; HOT FLASHES; HUMANS; MENOPAUSE; SELECTIVE ESTROGEN RECEPTOR MODULATORS;

EID: 84905023056     PISSN: 10723714     EISSN: 15300374     Source Type: Journal    
DOI: 10.1097/GME.0000000000000186     Document Type: Review

References (108)

1. Nair AR, Taylor HS. The mechanism of menstruation. In: Santoro NF, Neal-Perry G, eds. Amenorrhea: A Case-Based, Clinical Guide. New York, NY: Springer Science + Business Media LLC, 2010:21-34
2. Martin J, Dominguez F, Avila S, et al. Human endometrial receptivity: gene regulation. J Reprod Immunol 2002;55:131-139
3. Navot D, Margalioth EJ, Laufer N, Mor-Yosef S, Schenker JG. Asynchronous ovulation in human menopausal gonadotropin induction of ovulation for in vitro fertilization. Fertil Steril 1984;42:806-807
4. Riesewijk A, Martin J, van OR, et al. Gene expression profiling of human endometrial receptivity on days LH + 2 versus LH + 7 by microarray technology. Mol Hum Reprod 2003;9:253-264
5. Archer DF. Endometrial bleeding in postmenopausal women: with and without hormone therapy. Menopause 2011;18:416-420
6. The North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause 2012;19:257-271
7. National Osteoporosis Foundation. Clinicians Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2013
8. Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 2004;291:47-53
9. Lethaby A, Suckling J, Barlow D, Farquhar CM, Jepson RG, Roberts H. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004;CD000402
10. Archer DF, Pickar JH, Bottiglioni F. Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group. Obstet Gynecol 1994;83:686-692
11. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Womens Health Initiative randomized controlled trial. JAMA 2002;288:321-333
12. Breijer MC, Timmermans A, van Doorn HC, Mol BW, Opmeer BC. Diagnostic strategies for postmenopausal bleeding. Obstet Gynecol Int 2010;2010:850812
13. Botteman MF, Shah NP, Lian J, Pashos CL, Simon JA. A costeffectiveness evaluation of two continuous-combined hormone therapies for the management of moderate-to-severe vasomotor symptoms. Menopause 2004;11:343-355
14. Hall JM, McDonnell DP. Selective estrogen receptor modulators: from bench, to bedside, and back again. Menopausal Med 2008;16:S1-S6
15. Pickar JH, MacNeil T, Ohleth K. SERMs: progress and future perspectives. Maturitas 2010;67:129-138
16. Archer DF. Tissue-selective estrogen complexes: a promising option for the comprehensive management of menopausal symptoms. Drugs Aging 2010;27:533-544
17. Mirkin S, Pickar JH. The tissue-selective estrogen complex (TSEC): a promising new therapy for menopausal symptoms and postmenopausal osteoporosis. Curr Obstet Gynecol Rep 2012;1:50-58
18. Komm BS, Chines AA. An update on selective estrogen receptor modulators for the prevention and treatment of osteoporosis. Maturitas 2012;71:221-226
19. Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 1975; 293:1164-1167
20. Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol 1994;170:1213-1223
21. Pickar JH, Yeh I, Wheeler JE, Cunnane MF, Speroff L. Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;76:25-31
22. Pickar JH. The endometriumVfrom estrogens alone to TSECs. Climacteric 2009;12:463-477
23. Paganini-Hill A, Ross RK, Henderson BE. Endometrial cancer and patterns of use of oestrogen replacement therapy: a cohort study. Br J Cancer 1989;59:445-447
24. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995;85:304-313
25. Ziel HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 1975;293:1167-1170
26. Groothuis PG, Dassen HH, Romano A, Punyadeera C. Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human. Hum Reprod Update 2007;13:405-417
27. Koos RD. Minireview: Putting physiology back into estrogens mechanism of action. Endocrinology 2011;152:4481-4488
28. Samsioe G. The endometrium: effects of estrogen and estrogenprogestogen replacement therapy. Int J Fertil Menopausal Stud 1994; 39(suppl 2):84-92
29. Feeley KM, Wells M. Hormone replacement therapy and the endometrium. J Clin Pathol 2001;54:435-440
30. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1996;275:370-375
31. Archer DF. Neoplasia of the female reproductive tract: effects of hormone therapy. Endocrine 2004;24:259-263
32. Sturdee DW, Ulrich LG, Barlow DH, et al. The endometrial response to sequential and continuous combined oestrogen-progestogen replacement therapy. BJOG 2000;107:1392-1400
33. Beresford SA, Weiss NS, Voigt LF, McKnight B. Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestagen therapy in postmenopausal women. Lancet 1997;349:458-461
34. Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Womens Health Initiative randomized trial. JAMA 2003;290: 1739-1748
35. Sit AS, Modugno F, Hill LM, Martin J, Weissfeld JL. Transvaginal ultrasound measurement of endometrial thickness as a biomarker for estrogen exposure. Cancer Epidemiol Biomarkers Prev 2004;13:1459-1465
36. American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 426: the role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. Obstet Gynecol 2009;113:462-464
37. Goldstein SR. Significance of incidentally thick endometrial echo on transvaginal ultrasound in postmenopausal women. Menopause 2011; 18:434-436
38. Gull B, Karlsson B, Milsom I, Granberg S. Can ultrasound replace dilation and curettage? A longitudinal evaluation of postmenopausal bleeding and transvaginal sonographic measurement of the endometrium as predictors of endometrial cancer. Am J Obstet Gynecol 2003; 188:401-408
39. Christodoulakos GE, Botsis DS, Lambrinoudaki IV, et al. A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness. Maturitas 2006;53:413-423
40. Archer DF, Dorin M, Lewis V, Schneider DL, Pickar JH. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil Steril 2001;75:1080-1087
41. Hickey M, Fraser I. Human uterine vascular structures in normal and diseased states. Microsc Res Tech 2003;60:377-389
42. Hickey M, Ameratunga D, Marino JL. Unscheduled bleeding in continuous combined hormone therapy users. Maturitas 2011;70:400-403
43. Hickey M, Crewe J, Mahoney LA, Doherty DA, Fraser IS, Salamonsen LA. Mechanisms of irregular bleeding with hormone therapy: the role of matrix metalloproteinases and their tissue inhibitors. J Clin Endocrinol Metab 2006;91:3189-3198
44. Pinkerton JV, Goldstein SR. Endometrial safety: a key hurdle for selective estrogen receptor modulators in development. Menopause 2010; 17:642-653
45. Mirkin S, Komm BS. Tissue-selective estrogen complexes for postmenopausal women. Maturitas 2013;76:213-220
46. Dix CJ, Jordan VC. Modulation of rat uterine steroid hormone receptors by estrogen and antiestrogen. Endocrinology 1980;107:2011-2020
47. Holinka CF, Bressler RS, Zehr DR, Gurpide E. Comparison of effects of estertrol and tamoxifen with those of estriol and estradiol on the immature rat uterus. Biol Reprod 1980;22:913-926
48. Al-Jamal JH, Dubin NH. The effect of raloxifene on the uterine weight response in immature mice exposed to 17A-estradiol, 1,1,1-trichloro-2, 2-bis(p-chlorophenyl)ethane, and methoxychlor. Am J Obstet Gynecol 2000;182:1099-1102
49. Qu Q, Zheng H, Dahllund J, et al. Selective estrogenic effects of a novel triphenylethylene compound, FC1271a, on bone, cholesterol level, and reproductive tissues in intact and ovariectomized rats. Endocrinology 2000;141:809-820
50. Ke HZ, Paralkar VM, Grasser WA, et al. Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus and body composition in rat models. Endocrinology 1998; 139:2068-2076
51. Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146:3999-4008
52. Sikoski P, Register TC, Lees CJ, et al. Effects of two novel selective estrogen receptor modulators, raloxifene, tamoxifen, and ethinyl estradiol on the uterus, vagina and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis). Am J Obstet Gynecol 2007;196:75-77
53. Smith SY, Minck D, Jolette J, Chouinard L, Turner CH, Komm B. Bazedoxifene prevents ovariectomy-induced bone loss in the cynomolgus monkey [Abstract SA431]. J Bone Miner Res 2005;20(suppl 1):S174
54. Ethun KF, Wood CE, Cline JM, Register TC, Appt SE, Clarkson TB. Endometrial profile of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model. Menopause 2013; 20:777-784
55. Kulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 2011;152:3226-3232
56. Kharode YP, Bodine PV, Bex FJ, Komm BS. Skeletal and uterine effects of bazedoxifene in ovariectomized mice and rats with comparison to raloxifene and lasofoxifene [Abstract O-213]. Fertil Steril 2006;86:S91
57. 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; 150:1897-1903
58. de Villiers TJ, Chines AA, Palacios S, et al. Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int 2011;22:567-576
59. Palacios S, Silverman S, Levine AB, et al. Long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled study [Abstract 973]. Presented at: The Annual Meeting of the International Menopause Society World Congress on Menopause; June 8 to 11, 2011; Rome, Italy.
60. Palacios S, de Villiers TJ, De Cicco-Nardone F, et al. Reproductive safety of bazedoxifene in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study [Abstract 171]. Maturitas 2012;71:171
61. Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999;281:2189-2197
62. Goldstein SR, Scheele WH, Rajagopalan SK, Wilkie JL, Walsh BW, Parsons AK. A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium. Obstet Gynecol 2000; 95:95-103
63. Goldstein SR, Neven P, Cummings S, et al. Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial: 5-year gynecological outcomes. Menopause 2011;18:17-22
64. Portman DJ, Bachmann GA, Simon JA. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013;20:623-630
65. Simon JA, Lin VH, Radovich C, Bachmann GA. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause 2013;20:418-427
66. Miller PD, Chines AA, Christiansen C, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res 2008;23:525-535
67. 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 activecontrolled clinical trial. J Bone Miner Res 2008;23:1923-1934
68. 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
69. Vogel VG, Costantino 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
70. Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 1994;86:527-537
71. Dijkhuizen FP, Brolmann HA, Oddens BJ, Roumen RM, Coebergh JW, Heintz AP. Transvaginal ultrasonography and endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Maturitas 1996;25:45-50
72. Bese T, Kosebay D, Demirkiran F, Arvas M, Bese N, Mandel N. Ultrasonographic appearance of endometrium in postmenopausal breast cancer patients receiving tamoxifen. Eur J Obstet Gynecol Reprod Biol 1996;67:157-162
73. Pfizer Inc. Fablyn (lasofoxifene tartrate) 0.5 mg tablets. NDA 22-242. Reproductive Health Drugs Advisory Committee Briefing Document. Food and Drug Administration September 8, 2008. Available at: http://www.fda.gov/ohrms/ dockets/ac/08/briefing/2008-4381b1-02-Pfizer.pdf. Accessed October 11, 2013
74. Osphena [package insert]. Florham Park, NJ: Shionogi Inc, 2013
75. Silverman SL, Chines AA, Kendler DL, et al. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int 2012;23:351-363
76. Palacios S, de Villiers TJ, Nardone FC, et al. Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study. Maturitas 2013;76:81-87
77. Pinkerton JV, Archer DF, Utian WH, et al. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis. Menopause 2009;16:1102-1108
78. Christiansen C, Chesnut CH, Adachi JD, et al. Safety of bazedoxifene in a randomized, double-blind, placebo-and active-controlled phase 3 study of postmenopausal women with osteoporosis. BMC Musculoskelet Disord 2010;11:130
79. Komm BS. A new approach to menopausal therapy: the tissue selective estrogen complex. Reprod Sci 2008;15:984-992
80. Levine JP. Treating menopausal symptoms with a tissue-selective estrogen complex. Gend Med 2011;8:57-68
81. Berrodin TJ, Chang KC, Komm BS, Freedman LP, Nagpal S. Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol 2009;23:74-85
82. Chang KC, Wang Y, Bodine PV, Nagpal S, Komm BS. Gene expression profiling 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;118:117-124
83. Wardell SE, Kazmin D, McDonnell DP. Research resource: transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes. Mol Endocrinol 2012;26:1235-1248
84. Liu S, Han SJ, Smith CL. Cooperative activation of gene expression by agonists and antagonists mediated by estrogen receptor heteroligand dimer complexes. Mol Pharmacol 2013;83:1066-1077
85. Understanding cancer series: SERMs. National Cancer Institute at the National Institutes of Health 2013. Available at: http://www.cancer.gov/ cancertopics/understandingcancer. Accessed October 21, 2013
86. Davis SR, ONeill SM, Eden J, et al. Transition from estrogen therapy to raloxifene in postmenopausal women: effects on treatment satisfaction and the endometriumVa pilot study. Menopause 2004;11:167-175
87. Carranza-Lira S, Gooch AL, Saldivar N, Osterwalder MS. Climacteric symptom control after the addition of low-dose esterified conjugated estrogens to raloxifene standard doses. Int J Fertil Womens Med 2007;52:93-96
88. Stovall DW, Utian WH, Gass ML, et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause 2007;14:510-517
89. Kharode Y, Bodine PV, 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
90. Lewiecki EM. Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Expert Opin Investig Drugs 2007;16:1663-1672
91. Dey M, Lyttle CR, Pickar JH. Recent insights into the varying activity of estrogens. Maturitas 2000;34(suppl 2):S25-S33
92. Kulak J Jr, Ferriani RA, Komm BS, Taylor HS. Tissue selective estrogen complexes (TSECs) differentially modulate markers of proliferation and differentiation in endometrial cells. Reprod Sci 2013; 20:129-137
93. Komm BS, Vlasseros F, Samadfam R, Chouinard L, Smith SY. Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats. Bone 2011;49:376-386
94. Oliva P, Roncoroni C, Radaelli E, et al. Global profiling of TSEC proliferative potential by the use of a reporter mouse for proliferation. Reprod Sci 2013;20:119-128
95. 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;92:1039-1044
96. 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;92:1045-1052
97. Lobo RA, Pinkerton JV, Gass ML, et al. Evaluation of bazedoxifene/ conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009;92:1025-1038
98. Pickar JH, Yeh IT, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conjugated estrogens as a menopausal therapy. Fertil Steril 2009;92:1018-1024
99. Harvey JA, Pinkerton JV, Baracat EC, Shi H, Chines AA, Mirkin S. Breast density changes in a randomized controlled trial evaluating bazedoxifene/ conjugated estrogens. Menopause 2013;20:138-145
100. 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;16:1116-1124
101. Utian W, Yu H, Bobula J, Mirkin S, Olivier S, Pickar JH. Bazedoxifene/ conjugated estrogens and quality of life in postmenopausal women. Maturitas 2009;63:329-335
102. 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;17:281-289
103. 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;13:132-140
104. Gallagher JC, 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 double-blind, randomized, placebo-and active-controlled phase 3 study [Abstract 1133]. J Bone Miner Res 2011;26(suppl 1):S46
105. 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 [Abstract S-13]. Menopause 2011;18:1346
106. Pinkerton JV, Harvey JA, Pan K, et al. Breast effects of bazedoxifeneconjugated estrogens: a randomized controlled trial. Obstet Gynecol 2013;121:959-968
107. Mirkin S, Taylor HS, Archer DF, Pickar JH, Thompson J, Komm BS. Differential effects of bazedoxifene/conjugated estrogens and hormone therapy on the endometrium [Abstract]. Menopause 2012; 19:1374
108. Archer DF, Lobo RA, Pan K, Chines AA, Mirkin S. Safety and tolerability of bazedoxifene/conjugated estrogens in postmenopausal women: findings from a 1-year, randomized, placebo-and active-controlled, phase 3 trial [Abstract P-25]. Menopause 2011;18:1355-1356.