Fertility and Sterility
Volume 92, Issue 3 , Pages 1039-1044 , September 2009

Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women

  • David F. Archer, M.D.

      Affiliations

    • CONRAD Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia
    • Corresponding Author InformationReprint requests: David F. Archer, M.D., CONRAD Clinical Research Center, Eastern Virginia Medical School, 601 Colley Avenue, Norfolk, VA 23507 (FAX: 757-446-8998).
    • ,
  • Vivian Lewis, M.D.

      Affiliations

    • University of Rochester Medical Center, Rochester, New York
    • ,
  • Bruce R. Carr, M.D.

      Affiliations

    • University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Sophie Olivier, M.D.

      Affiliations

    • Wyeth Research, Collegeville, Pennsylvania
    • ,
  • James H. Pickar, M.D.

      Affiliations

    • Wyeth Research, Collegeville, Pennsylvania

Received 18 September 2008 ,Revised 8 May 2009 ,Accepted 22 May 2009.

References 

  1. Pinkerton JV, Zion AS. Vasomotor symptoms in menopause: where we've been and where we're going. J Womens Health (Larchmt). 2006;15:135–145
  2. Gambacciani M, Vacca F. Postmenopausal osteoporosis and hormone replacement therapy. Minerva Med. 2004;95:507–520
  3. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;CD002978
  4. Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al. 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
  5. Hammond CB, Jelovsek FR, Lee KL, Creasman WT, Parker RT. Effects of long-term estrogen replacement therapy. II. Neoplasia. Am J Obstet Gynecol. 1979;133:537–547
  6. Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med. 1975;293:1164–1167
  7. Pickar JH, Yeh IT, Wheeler JE, Cunnane MF, Speroff L. Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results. Fertil Steril. 2003;80:1234–1240
  8. Manonai J, Theppisai U, Suchartwatnachai C, Jetsawangsri T, Chittacharoen A. Compliance with hormone replacement therapy in Thai women. Maturitas. 2003;44:201–205
  9. Wattanakumtornkul S, Chichareon S, Geater A, Suwan K. Compliance with hormone replacement therapy at Songklanagarind Hospital. J Obstet Gynaecol Res. 2003;29:380–387
  10. 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
  11. Komm BS, Lyttle CR. Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann N Y Acad Sci. 2001;949:317–326
  12. 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
  13. Ronkin S, Northington R, Baracat E, Nunes MG, Archer DF, Constantine G, et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol. 2005;105:1397–1404
  14. Komm BS. A new approach to menopausal therapy: the tissue selective estrogen complex. Reprod Sci. 2008;15:984–992
  15. Lewiecki EM. Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Expert Opin Investig Drugs. 2007;16:1663–1672
  16. 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;23:75–85
  17. 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
  18. Crabtree JS, Peano BJ, Zhang X, Komm BS, Winneker RC, Harris HA. Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland. Mol Cell Endocrinol. 2008;287:40–46
  19. 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
  20. Stovall DW, Utian WH, Gass ML, Qu Y, Muram D, Wong M, et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause. 2007;14:510–517
  21. Valiati B, Capp E, Edelweiss MI, de Freitas FM, Wender MC. Effect of raloxifene and low-dose percutaneous 17beta-estradiol on menopause symptoms and endometrium—a randomized controlled trial. Maturitas. 2009;62:81–84
  22. Lobo RA, Pinkerton JV, Gass MLS, Dorin MH, Ronkin S, Pickar JH, 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
  23. 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;92:1018–1024
  24. Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex (TSEC) of bazedoxifene/conjugated estrogens (BZA/CE) for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009;92:1045–1052
  25. 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
  26. Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA. Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability. BJOG. 2007;114:1522–1529
  27. Papaioannou A, Kennedy CC, Dolovich L, Lau E, Adachi JD. Patient adherence to osteoporosis medications: problems, consequences and management strategies. Drugs Aging. 2007;24:37–55
  28. Guay MP, Dragomir A, Pilon D, Moride Y, Perreault S. Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication. Pharmacoepidemiol Drug Saf. 2007;16:17–27
  29. 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
  30. Vashisht A, Wadsworth F, Carey A, Carey B, Studd J. Bleeding profiles and effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of a continuous combined hormone replacement regime. BJOG. 2005;112:1402–1406
  31. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997;389:753–758
  32. Katzenellenbogen BS, Choi I, Delage-Mourroux R, Ediger TR, Martini PGV, Montano M, et al. Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology. J Steroid Biochem Mol Biol. 2000;74:279–285
  33. Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor transcription and transactivation: estrogen receptor alpha and estrogen receptor beta: regulation by selective estrogen receptor modulators and importance in breast cancer. Breast Cancer Res. 2000;2:335–344

 D.F.A. has received research grants from and is a consultant and speaker for Wyeth. V.L. has received research grants from Wyeth. B.R.C. has served as a lecturer for Wyeth and Novo Nordisk and has received research grants from Duramed, Neurocrine, and Boehringer Ingelheim. S.O. was previously an employee of Wyeth. J.H.P. is an employee of Wyeth.

 Sponsored by Wyeth Research, Collegeville, PA.

 Portions of this work were presented at the 89th Annual Meeting of the Endocrine Society; June 2–5, 2007; Toronto, Ontario, Canada. Abstract P1-350.

 The Selective estrogen Menopause And Response to Therapy (SMART)-1 trial was a 2-year, outpatient, randomized, double-blind, placebo- and active-controlled, phase III study conducted at 94 sites in the United States, Europe, and Brazil (Unique trial number: NCT00675688; Trial registration date: 05/09/2008).

PII: S0015-0282(09)01303-X

doi: 10.1016/j.fertnstert.2009.05.093

Fertility and Sterility
Volume 92, Issue 3 , Pages 1039-1044 , September 2009

Article Tools

* Image Usage & Resolution