The tissue selective estrogen complex: A promising new menopausal therapy

Pharmaceuticals

Volumn 5, Issue 9, 2012, Pages 899-924

  Komm, Barry S ^a   Mirkin, Sebastian ^a  

^a PFIZER INC   (United States)

Author keywords

Bazedoxifene; Conjugated estrogens; Hormone therapy; Menopause; Tissue selective estrogen complex (TSEC)

Indexed keywords

BAZEDOXIFENE; BAZEDOXIFENE PLUS CONJUGATED ESTROGEN; CONJUGATED ESTROGEN; CONJUGATED ESTROGEN PLUS MEDROXYPROGESTERONE ACETATE; ETHINYLESTRADIOL PLUS NORETHISTERONE; GESTAGEN; PLACEBO; SELECTIVE ESTROGEN RECEPTOR MODULATOR; TISSUE SELECTIVE ESTROGEN COMPLEX; UNCLASSIFIED DRUG;

AMENORRHEA; BONE MASS; BREAST; BREAST CANCER; BREAST TENDERNESS; DISEASE SEVERITY; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; ENDOMETRIAL DISEASE; ENDOMETRIUM; ENDOMETRIUM HYPERPLASIA; FEMALE GENITAL SYSTEM; HORMONE SUBSTITUTION; HOT FLUSH; HUMAN; MASTALGIA; MENOPAUSAL SYNDROME; MENOPAUSE; PATIENT SATISFACTION; QUALITY OF LIFE; REVIEW; THROMBOEMBOLISM; UNSPECIFIED SIDE EFFECT; VAGINA ATROPHY; VENOUS THROMBOEMBOLISM;

EID: 84866548549     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph5090899     Document Type: Review

References (106)

1. Burger, H.G.; Dudley, E.C.; Robertson, D.M.; Dennerstein, L. Hormonal changes in the menopause transition. Recent Prog. Horm. Res. 2002, 57, 257-275.
2. Burger, H.G. The endocrinology of the menopause. Maturitas 1996, 23, 129-136.
3. Levine, J.P. Treating menopausal symptoms with a tissue-selective estrogen complex. Gend. Med. 2011, 8, 57-68.
4. Lewis, V. Undertreatment of menopausal symptoms and novel options for comprehensive management. Curr. Med. Res. Opin. 2009, 25, 2689-2698.
5. Dennerstein, L.; Dudley, E.C.; Hopper, J.L.; Guthrie, J.R.; Burger, H.G. A prospective population-based study of menopausal symptoms. Obstet. Gynecol. 2000, 96, 351-358.
6. Riggs, B.L.; Khosla, S.; Melton, L.J., III. A unitary model for involutional osteoporosis: Estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J. Bone Miner. Res. 1998, 13, 763-773.
7. National Osteoporosis Foundation. Fast facts on osteoporosis. Available online: http://www.nof.org/node/40/ (accessed on 17 November 2011).
8. Utian, W.H. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: A comprehensive review. Health. Qual. Life Outcomes 2005, 3, 47.
9. North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012, 19, 257-271.
10. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 Position statement of The North American Menopause Society. Menopause 2010, 17, 25-54.
11. 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.
12. Smith, D.C.; Prentice, R.; Thompson, D.J.; Herrmann, W.L. Association of exogenous estrogen and endometrial carcinoma. N. Engl. J. Med. 1975, 293, 1164-1167.
13. Weiderpass, E.; Adami, H.O.; Baron, J.A.; Magnusson, C.; Bergstrom, R.; Lindgren, A.; Correia, N.; Persson, I. Risk of endometrial cancer following estrogen replacement with and without progestins. J. Natl. Cancer Inst. 1999, 91, 1131-1137.
14. Ziel, H.K.; Finkle, W.D. Increased risk of endometrial carcinoma among users of conjugated estrogens. N. Engl. J. Med. 1975, 293, 1167-1170.
15. North American Menopause Society. Role of progestogen in hormone therapy for postmenopausal women: Position statement of The North American Menopause Society. Menopause 2003, 10, 113-132.
16. 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, 1065-1079.
17. MacLennan, A.H.; Broadbent, J.L.; Lester, S.; Moore, V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst. Rev. 2004, CD002978.
18. Greendale, G.A.; Reboussin, B.A.; Hogan, P.; Barnabei, V.M.; Shumaker, S.; Johnson, S.; Barrett-Connor, E. Symptom relief and side effects of postmenopausal hormones: Results from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet. Gynecol. 1998, 92, 982-988.
19. Pornel, B.; Spielmann, D. A study of the control of climacteric symptoms in postmenopausal women following sequential regimens of 1 mg 17b-estradiol and trimegestone compared with a regimen containing 1 mg estradiol valerate and norethisterone over a 2-year period. Gynecol. Endocrinol. 2005, 21, 74-81.
20. Gambacciani, M.; Spielmann, D.; Genazzani, A.R. Efficacy on climacteric symptoms of a continuous combined regimen of 1 mg 17b-estradiol and trimegestone versus two regimens combining 1 or 2 mg 17b-estradiol and norethisterone acetate. Gynecol. Endocrinol. 2005, 21, 65-73.
21. Schurmann, R.; Holler, T.; Benda, N. Estradiol and drospirenone for climacteric symptoms in postmenopausal women: A double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens. Climacteric 2004, 7, 189-196.
22. Rowan, J.P.; Simon, J.A.; Speroff, L.; Ellman, H. Effects of low-dose norethindrone acetate plus ethinyl estradiol (0.5 mg/2.5 mg) in women with postmenopausal symptoms: Updated analysis of three randomized, controlled trials. Clin. Ther. 2006, 28, 921-932.
23. Cardozo, L.; Bachmann, G.; McClish, D.; Fonda, D.; Birgerson, L. Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: Second report of the Hormones and Urogenital Therapy Committee. Obstet. Gynecol. 1998, 92, 722-727.
24. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 Position statement of The North American Menopause Society. Menopause 2007, 14, 357-369.
25. Dorr, M.B.; Nelson, A.L.; Mayer, P.R.; Ranganath, R.P.; Norris, P.M.; Helzner, E.C.; Preston, R.A. Plasma estrogen concentrations after oral and vaginal estrogen administration in women with atrophic vaginitis. Fertil. Steril. 2010, 94, 2365-2368.
26. Bachmann, G.; Bouchard, C.; Hoppe, D.; Ranganath, R.; Altomare, C.; Vieweg, A.; Graepel, J.; Helzner, E. Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally. Menopause 2009, 16, 719-727.
27. Jackson, R.D.; Wactawski-Wende, J.; LaCroix, A.Z.; Pettinger, M.; Yood, R.A.; Watts, N.B.; Robbins, J.A.; Lewis, C.E.; Beresford, S.A.; Ko, M.G.; et al. Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the women's health initiative randomized trial. J. Bone Miner. Res. 2006, 21, 817-828.
28. Cauley, J.A.; Robbins, J.; Chen, Z.; Cummings, S.R.; Jackson, R.D.; LaCroix, A.Z.; LeBoff, M.; Lewis, C.E.; McGowan, J.; Neuner, J.; et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: The Women's Health Initiative randomized trial. JAMA 2003, 290, 1729-1738.
29. Lindsay, R.; Gallagher, J.C.; Kleerekoper, M.; Pickar, J.H. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002, 287, 2668-2676.
30. Torgerson, D.J.; Bell-Syer, S.E. Hormone replacement therapy and prevention of nonvertebral fractures: A meta-analysis of randomized trials. JAMA 2001, 285, 2891-2897.
31. Wells, G.; Tugwell, P.; Shea, B.; Guyatt, G.; Peterson, J.; Zytaruk, N.; Robinson, V.; Henry, D.; O'Connell, D.; Cranney, A. Meta-analyses of therapies for postmenopausal osteoporosis. V. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr. Rev. 2002, 23, 529-539.
32. Hays, J.; Ockene, J.K.; Brunner, R.L.; Kotchen, J.M.; Manson, J.E.; Patterson, R.E.; Aragaki, A.K.; Shumaker, S.A.; Brzyski, R.G.; LaCroix, A.Z.; et al. Effects of estrogen plus progestin on health-related quality of life. N. Engl. J. Med. 2003, 348, 1839-1854.
33. Brunner, R.L.; Gass, M.; Aragaki, A.; Hays, J.; Granek, I.; Woods, N.; Mason, E.; Brzyski, R.; Ockene, J.; Assaf, A.; et al. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: Results from the Women's Health Initiative Randomized Clinical Trial. Arch. Intern. Med. 2005, 165, 1976-1986.
34. Polo-Kantola, P.; Erkkola, R.; Helenius, H.; Irjala, K.; Polo, O. When does estrogen replacement therapy improve sleep quality? Am. J. Obstet. Gynecol. 1998, 178, 1002-1009.
35. Barnabei, V.M.; Grady, D.; Stovall, D.W.; Cauley, J.A.; Lin, F.; Stuenkel, C.A.; Stefanick, M.L.; Pickar, J.H. Menopausal symptoms in older women and the effects of treatment with hormone therapy. Obstet. Gynecol. 2002, 100, 1209-1218.
36. Gelfand, M.M.; Moreau, M.; Ayotte, N.J.; Hilditch, J.R.; Wong, B.A.; Lau, C.Y. Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: A placebo-controlled study. Menopause 2003, 10, 29-36.
37. Hlatky, M.A.; Boothroyd, D.; Vittinghoff, E.; Sharp, P.; Whooley, M.A. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: Results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA 2002, 287, 591-597.
38. Haines, C.J.; Yim, S.F.; Chung, T.K.; Lam, C.W.; Lau, E.W.; Ng, M.H.; Chin, R.; Lee, D.T. A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women. Maturitas 2003, 44, 207-214.
39. Rossouw, J.E.; Anderson, G.L.; Prentice, R.L.; LaCroix, A.Z.; Kooperberg, C.; Stefanick, M.L.; Jackson, R.D.; Beresford, S.A.; Howard, B.V.; Johnson, K.C.; et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002, 288, 321-333.
40. Hsia, J.; Criqui, M.H.; Herrington, D.M.; Manson, J.E.; Wu, L.; Heckbert, S.R.; Allison, M.; McDermott, M.M.; Robinson, J.; Masaki, K. Conjugated equine estrogens and peripheral arterial disease risk: The Women's Health Initiative. Am. Heart J. 2006, 152, 170-176.
41. Anderson, G.L.; Limacher, M.; Assaf, A.R.; Bassford, T.; Beresford, S.A.; Black, H.; Bonds, D.; Brunner, R.; Brzyski, R.; Caan, B.; et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: The Women's Health Initiative randomized controlled trial. JAMA 2004, 291, 1701-1712.
42. Rossouw, J.E.; Prentice, R.L.; Manson, J.E.; Wu, L.; Barad, D.; Barnabei, V.M.; Ko, M.; LaCroix, A.Z.; Margolis, K.L.; Stefanick, M.L. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007, 297, 1465-1477.
43. Manson, J.E.; Allison, M.A.; Rossouw, J.E.; Carr, J.J.; Langer, R.D.; Hsia, J.; Kuller, L.H.; Cochrane, B.B.; Hunt, J.R.; Ludlam, S.E.; et al. Estrogen therapy and coronary-artery calcification. N. Engl. J. Med. 2007, 356, 2591-2602.
44. Hendrix, S.L.; Wassertheil-Smoller, S.; Johnson, K.C.; Howard, B.V.; Kooperberg, C.; Rossouw, J.E.; Trevisan, M.; Aragaki, A.; Baird, A.E.; Bray, P.F.; et al. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006, 113, 2425-2434.
45. Curb, J.D.; Prentice, R.L.; Bray, P.F.; Langer, R.D.; van Horn, L.; Barnabei, V.M.; Bloch, M.J.; Cyr, M.G.; Gass, M.; Lepine, L.; et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch. Intern. Med. 2006, 166, 772-780.
46. Stefanick, M.L.; Anderson, G.L.; Margolis, K.L.; Hendrix, S.L.; Rodabough, R.J.; Paskett, E.D.; Lane, D.S.; Hubbell, F.A.; Assaf, A.R.; Sarto, G.E.; et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006, 295, 1647-1657.
47. LaCroix, A.Z.; Chlebowski, R.T.; Manson, J.E.; Aragaki, A.K.; Johnson, K.C.; Martin, L.; Margolis, K.L.; Stefanick, M.L.; Brzyski, R.; Curb, J.D.; et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: A randomized controlled trial. JAMA 2011, 305, 1305-1314.
48. Cushman, M.; Kuller, L.H.; Prentice, R.; Rodabough, R.J.; Psaty, B.M.; Stafford, R.S.; Sidney, S.; Rosendaal, F.R. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004, 292, 1573-1580.
49. Wassertheil-Smoller, S.; Hendrix, S.L.; Limacher, M.; Heiss, G.; Kooperberg, C.; Baird, A.; Kotchen, T.; Curb, J.D.; Black, H.; Rossouw, J.E.; et al. Effect of estrogen plus progestin on stroke in postmenopausal women: The Women's Health Initiative: A randomized trial. JAMA 2003, 289, 2673-2684.
50. Topal, N.B.; Ayhan, S.; Topal, U.; Bilgin, T. Effects of hormone replacement therapy regimens on mammographic breast density: The role of progestins. J. Obstet. Gynaecol. Res. 2006, 32, 305-308.
51. Kaewrudee, S.; Anuwutnavin, S.; Kanpittaya, J.; Soontrapa, S.; Sakondhavat, C. Effect of estrogen-progestin and estrogen on mammographic density. J. Reprod. Med. 2007, 52, 513-520.
52. Santen, R. Menopausal hormone therapies: Their effect on mammographic density and breast cancer risk. Gynecol. Endocrinol. 2005, 21, 12-16.
53. Chen, F.P.; Cheung, Y.C.; Soong, Y.K. Factors that influence changes in mammographic density with postmenopausal hormone therapy. Taiwan J. Obstet. Gynecol. 2010, 49, 413-418.
54. Boyd, N.F.; Rommens, J.M.; Vogt, K.; Lee, V.; Hopper, J.L.; Yaffe, M.J.; Paterson, A.D. Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol. 2005, 6, 798-808.
55. McCormack, V.A.; dos Santos Silva, I. Breast density and parenchymal patterns as markers of breast cancer risk: A meta-analysis. Cancer Epidemiol. Biomarkers Prev. 2006, 15, 1159-1169.
56. Pinsky, R.W.; Helvie, M.A. Mammographic breast density: Effect on imaging and breast cancer risk. J. Natl. Compr. Canc. Netw. 2010, 8, 1157-1164.
57. Anderson, G.L.; Chlebowski, R.T.; Rossouw, J.E.; Rodabough, R.J.; McTiernan, A.; Margolis, K.L.; Aggerwal, A.; David, C.J.; Hendrix, S.L.; Allan, H.F.; et al. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006, 55, 103-115.
58. Chlebowski, R.T.; Anderson, G.L.; Gass, M.; Lane, D.S.; Aragaki, A.K.; Kuller, L.H.; Manson, J.E.; Stefanick, M.L.; Ockene, J.; Sarto, G.E.; et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010, 304, 1684-1692.
59. Manonai, J.; Theppisai, U.; Suchartwatnachai, C.; Jetsawangsri, T.; Chittacharoen, A. Compliance with hormone replacement therapy in Thai women. Maturitas 2003, 44, 201-205.
60. Barnabei, V.M.; Cochrane, B.B.; Aragaki, A.K.; Nygaard, I.; Williams, R.S.; McGovern, P.G.; Young, R.L.; Wells, E.C.; O'Sullivan, M.J.; Chen, B.; et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative. Obstet. Gynecol. 2005, 105, 1063-1073.
61. Crandall, C.J.; Aragaki, A.K.; Cauley, J.A.; McTiernan, A.; Manson, J.E.; Anderson, G.; Chlebowski, R.T. Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women's health initiative clinical trials. Breast Cancer Res. Treat. 2012, 132, 275-285.
62. Guyton, A., Hall, J., Eds. Textbook of Medical Physiology; W.B. Saunders Company: Philadelphia, PA, USA, 1996; pp. 1017-1032.
63. Fournier, A.; Berrino, F.; Clavel-Chapelon, F. Unequal risks for breast cancer associated with different hormone replacement therapies: Results from the E3N cohort study. Breast Cancer Res. Treat. 2008, 107, 103-111.
64. Nelson, H.D.; Vesco, K.K.; Haney, E.; Fu, R.; Nedrow, A.; Miller, J.; Nicolaidis, C.; Walker, M.; Humphrey, L. Nonhormonal therapies for menopausal hot flashes: Systematic review and meta-analysis. JAMA 2006, 295, 2057-2071.
65. North American Menopause Society. The role of soy isoflavones in menopausal health: Report of The North American Menopause Society/Wulf H. Utian Translational Science Symposium in Chicago, IL (October 2010). Menopause 2011, 18, 732-753.
66. Howes, L.G.; Howes, J.B.; Knight, D.C. Isoflavone therapy for menopausal flushes: A systematic review and meta-analysis. Maturitas 2006, 55, 203-211.
67. Ettinger, B.; Black, D.M.; Mitlak, B.H.; Knickerbocker, R.K.; Nickelsen, T.; Genant, H.K.; Christiansen, C.; Delmas, P.D.; Zanchetta, J.R.; Stakkestad, J.; et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 1999, 282, 637-645.
68. Komm, B.S. A new approach to menopausal therapy: The tissue selective estrogen complex. Reprod. Sci. 2008, 15, 984-992.
69. McDonnell, D.P.; Connor, C.E.; Wijayaratne, A.; Chang, C.Y.; Norris, J.D. Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators. Recent Prog. Horm. Res. 2002, 57, 295-316.
70. 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, 6084-6091.
71. Komm, B.S.; Vlasseros, F.; Samadfam, R.; Chouinard, L.; Smith, S.Y. Skeletal effects of bazedoxifene paired with conjugated estrogens in ovariectomized rats. Bone 2011, 49, 376-386.
72. Peano, B.J.; Crabtree, J.S.; Komm, B.S.; Winneker, R.C.; Harris, H.A. Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. Endocrinology 2009, 150, 1897-1903.
73. Stovall, D.W.; Utian, W.H.; Gass, M.L.; Qu, Y.; Muram, D.; Wong, M.; Plouffe, L., Jr. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause 2007, 14, 510-517.
74. Davis, S.R.; O'Neill, S.M.; Eden, J.; Baber, R.; Ekangaki, A.; Stocks, J.M.; Thiebaud, D. Transition from estrogen therapy to raloxifene in postmenopausal women: Effects on treatment satisfaction and the endometrium-a pilot study. Menopause 2004, 11, 167-175.
75. Carranza-Lira, S.; Gooch, A.L.; Saldivar, N.; Osterwalder, M.S. 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.
76. Pinkerton, J.V.; Shifren, J.L.; La, V.J.; Rosen, A.; Roesinger, M.; Siddhanti, S. Influence of raloxifene on the efficacy of an estradiol-releasing ring for treating vaginal atrophy in postmenopausal women. Menopause 2003, 10, 45-52.
77. Valiati, B.; Capp, E.; Edelweiss, M.I.; de Freitas, F.M.; Wender, M.C. Effect of raloxifene and low-dose percutaneous 17beta-estradiol on menopause symptoms and endometrium-A randomized controlled trial. Maturitas 2009, 62, 81-84.
78. Archer, D.F.; Lewis, V.; Carr, B.R.; Olivier, S.; Pickar, J.H. Bazedoxifene/conjugated estrogens (BZA/CE): Incidence of uterine bleeding in postmenopausal women. Fertil. Steril. 2009, 92, 1039-1044.
79. Lindsay, R.; Gallagher, J.C.; Kagan, R.; Pickar, J.H.; 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.
80. Lobo, R.A.; Pinkerton, J.V.; Gass, M.L.; Dorin, M.H.; Ronkin, S.; Pickar, J.H.; Constantine, G. 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.
81. Pickar, J.H.; 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, 1018-1024.
82. Pinkerton, J.V.; Utian, W.H.; Constantine, G.D.; Olivier, S.; Pickar, J.H. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: A randomized, controlled trial. Menopause 2009, 16, 1116-1124.
83. Utian, W.; Yu, H.; Bobula, J.; Mirkin, S.; Olivier, S.; Pickar, J.H. Bazedoxifene/conjugated estrogens and quality of life in postmenopausal women. Maturitas 2009, 63, 329-335.
84. 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.
85. Kagan, R.; Williams, R.S.; Pan, K.; Mirkin, S.; Pickar, J.H. 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.
86. Fenton, A.; Chines, A.; Mirkin, S. Endometrial safety and bleeding profile of bazedoxifene paired with conjugated estrogens: Results from 2 years of therapy. Presentation at the 4th Triennial Scientific Meeting of the Asia Pacific Menopause Federation, Sydney, Australia, 26-29 September 2010.
87. Fenton, A.; Chines, A.; Mirkin, S. Effect of bazedoxifene paired with conjugated estrogens on vasomotor symptoms over 2 years of therapy. Presented at the 4th Triennial Scientific Meeting of the Asia Pacific Menopause Federation, Sydney, Australia, 26-29 September 2010.
88. Harvey, J.A.; Pinkerton, J.V.; Baracat, E.C.; Shi, H.; Mirkin, S.; Chines, A.A. Evaluation of changes in mammographic breast density associated with bazedoxifene/conjugated estrogens in postmenopausal women. Endocr. Rev. 2011, 32, (Abstract) P1-P79.
89. Yu, H.; Racketa, J.; Mirkin, S.; Chines, A. Hot flush symptom-free days with bazedoxifene/conjugated estrogens in a randomized, controlled trial of postmenopausal women. Menopause 2010, 17, 1238, Abstract P-56.
90. Silverman, S.L.; Christiansen, C.; Genant, H.K.; Vukicevic, S.; Zanchetta, J.R.; de Villiers, T.J.; Constantine, G.D.; Chines, A.A. 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.
91. Haines, C.J.; Pan, K.; Mirkin, S.; Chines, A.A. Safety and tolerability of bazedoxifene and conjugated estrogens: Pooled analysis from the Selective estrogens, Menopause And Response to Therapy (SMART)-1, SMART-2, and SMART-3 trials. Poster presented at the 4th Triennial Scientific Meeting of the Asia Pacific Menopause Federation, Sydney, Australia, 26-29 September 2010.
92. Christiansen, C.; Chesnut, C.H., III; Adachi, J.D.; Brown, J.P.; Fernandes, C.E.; Kung, A.W.; Palacios, S.; Levine, A.B.; Chines, A.A.; Constantine, G.D. 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.
93. Pinkerton, J.V.; Archer, D.F.; Utian, W.H.; Menegoci, J.C.; Levine, A.B.; Chines, A.A.; Constantine, G.D. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis. Menopause 2009, 16, 1102-1108.
94. Archer, D.F.; Pinkerton, J.V.; Utian, W.H.; Menegoci, J.C.; de Villiers, T.J.; Yuen, C.K.; Levine, A.B.; Chines, A.A.; Constantine, G.D. Bazedoxifene, a selective estrogen receptor modulator: Effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. Menopause 2009, 16, 1109-1115.
95. 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, 1193-1196.
96. Pinkerton, J.A.; Constantine, G.D.; Komm, B.S.; Yu, H.; Pickar, J.H. Breast effects of bazedoxifene/conjugated estrogens in a randomized, controlled trial of postmenopausal women. Menopause 2008, 15, 1221, Abstract P-46.
97. Archer, D.F.; Dorin, M.; Lewis, V.; Schneider, D.L.; Pickar, J.H. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil. Steril. 2001, 75, 1080-1087.
98. Archer, D.F.; Pickar, J.H.; 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.
99. Crandall, C.J.; Karlamangla, A.; Huang, M.H.; Ursin, G.; Guan, M.; Greendale, G.A. Association of new-onset breast discomfort with an increase in mammographic density during hormone therapy. Arch. Intern. Med. 2006, 166, 1578-1584.
100. Wattanakumtornkul, S.; Chichareon, S.; Geater, A.; Suwan, K. Compliance with hormone replacement therapy at Songklanagarind Hospital. J. Obstet. Gynaecol. Res. 2003, 29, 380-387.
101. Komm, B.S.; Lyttle, C.R. Developing a SERM: Stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann. NY Acad. Sci. 2001, 949, 317-326.
102. Komm, B.S.; Kharode, Y.P.; Bodine, P.V.; Harris, H.A.; Miller, C.P.; Lyttle, C.R. Bazedoxifene acetate: A selective estrogen receptor modulator with improved selectivity. Endocrinology 2005, 146, 3999-4008.
103. 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 double-blind, randomized, placebo- and active-controlled phase 3 study. J. Bone Miner. Res. 2011, 26, S46, Abstract 1133.
104. Pinkerton, J.V.; Pan, K.; Abraham, L.; Racketa, J.; Chines, A.A.; Mirkin, S. Effects of bazedoxifene/conjugated estrogens on sleep parameters and health-related quality of life in postmenopausal women. Menopause 2011, 18, 1346, Abstract S-13.
105. Archer, D.F.; Lobo, R.A.; Pan, K.; Chines, A.A.; 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. Menopause 2011, 18, 1355-1356, Abstract P-25.
106. Harvey, J.A.; Pinkerton, J.V.; Pan, K.; Thompson, J.R.; Ryan, K.A.; Mirkin, S.; Chines, A.A. The effects of bazedoxifene/conjugated estrogens on breast density in postmenopausal women. Menopause 2011, 18, 1342, Abstract S-1.