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Conjugated estrogens for the treatment of menopausal symptoms: a review of safety data

, MD, , PhD & , MD

Bibliography

  • Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest 2006;116:561-70
  • Heldring N, Pike A, Andersson S, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007;87:905-31
  • Loose-Mitchell DS, Stancel GM. Estrogens and progestins. In: Hardman JG, Limbird LE, Goodman Gilman A, editors. Goodman & Gilman's the pharmacological basis of therapeutics. McGraw-Hill; New York, NY: 2001
  • Pal R, Chaturvedi R, Kamboj KK, et al. Estrogen receptors in rat bone: their interaction with estrogen receptor modulators. Endocr Res 2001;27:283-91
  • Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999;340:1801-11
  • Gundlah C, Kohama SG, Mirkes SJ, et al. Distribution of estrogen receptor beta (ERbeta) mRNA in hypothalamus, midbrain and temporal lobe of spayed macaque: continued expression with hormone replacement. Brain Res Mol Brain Res 2000;76:191-204
  • Kuiper GG, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863-70
  • Ostlund H, Keller E, Hurd YL. Estrogen receptor gene expression in relation to neuropsychiatric disorders. Ann NY Acad Sci 2003;1007:54-63
  • Pelletier G, El-Alfy M. Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab 2000;85:4835-40
  • Stossi F, Barnett DH, Frasor J, et al. Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: distinct and common target genes for these receptors. Endocrinology 2004;145:3473-86
  • Leitman DC, Paruthiyil S, Yuan C, et al. Tissue-specific regulation of genes by estrogen receptors. Semin Reprod Med 2012;30:14-22
  • McDonnell DP, Wardell SE. The molecular mechanisms underlying the pharmacological actions of ER modulators: implications for new drug discovery in breast cancer. Curr Opin Pharmacol 2010;10:620-8
  • Jordan VC, O'Malley BW. Selective estrogen-receptor modulators and antihormonal resistance in breast cancer. J Clin Oncol 2007;25:5815-24
  • North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257-71
  • Vogelvang TE, van der Mooren MJ, Mijatovic V. Hormone replacement therapy, selective estrogen receptor modulators, and tissue-specific compounds: cardiovascular effects and clinical implications. Treat Endocrinol 2004;3:105-15
  • Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995;273:199-208
  • Dey M, Lyttle CR, Pickar JH. Recent insights into the varying activity of estrogens. Maturitas 2000;34(Suppl 2):S25-33
  • Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;75:1065-79
  • 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
  • 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
  • Jackson RD, Wactawski-Wende J, LaCroix AZ, 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;21:817-28
  • Mueck AO, Seeger H, Wallwiener D. Comparison of the proliferative effects of estradiol and conjugated equine estrogens on human breast cancer cells and impact of continuous combined progestogen addition. Climacteric 2003;6:221-7
  • Wood CE, Clarkson TB, Chen H, et al. Comparative effects of oral conjugated equine estrogens and micronized 17beta-estradiol on breast proliferation: a retrospective analysis. Menopause 2008;15:890-8
  • Crandall CJ, Aragaki AK, Cauley JA, et al. Breast tenderness after initiation of conjugated equine estrogens and mammographic density change. Breast Cancer Res Treat 2012;131:969-79
  • Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997;350:1047-59
  • Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003;362:419-27
  • Shapiro S. The million women study: potential biases do not allow uncritical acceptance of the data. Climacteric 2004;7:3-7
  • Whitehead M, Farmer R. The million women study: a critique. Endocrine 2004;24:187-93
  • Bromley SE, de Vries CS, Farmer RD. Utilisation of hormone replacement therapy in the United Kingdom. A descriptive study using the general practice research database. BJOG 2004;111:369-76
  • Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 2006;166:1027-32
  • 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
  • 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
  • Prentice RL, Chlebowski RT, Stefanick ML, et al. Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study. Am J Epidemiol 2008;167:1407-15
  • Smith DC, Prentice R, Thompson DJ, Herrmann WL. Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 1975;293:1164-7
  • Ziel HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 1975;293:1167-70
  • Grady D, Gebretsadik T, Kerlikowske K, et al. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 1995;85:304-13
  • Pickar JH, Yeh IT, Wheeler JE, et al. Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results. Fertil Steril 2003;80:1234-40
  • Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1996;275:370-5
  • 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;83:686-92
  • Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-12
  • Ritenbaugh C, Stanford JL, Wu L, et al. Conjugated equine estrogens and colorectal cancer incidence and survival: the Women's Health Initiative randomized clinical trial. Cancer Epidemiol Biomarkers Prev 2008;17:2609-18
  • 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
  • Delellis Henderson K, Duan L, Sullivan-Halley J, et al. Menopausal hormone therapy use and risk of invasive colon cancer: the California Teachers Study. Am J Epidemiol 2010;171:415-25
  • Morois S, Fournier A, Clavel-Chapelon F, et al. Menopausal hormone therapy and risks of colorectal adenomas and cancers in the French E3N prospective cohort: true associations or bias? Eur J Epidemiol 2012;27:439-52
  • Chlebowski RT, Anderson GL, Manson JE, et al. Lung cancer among postmenopausal women treated with estrogen alone in the women's health initiative randomized trial. J Natl Cancer Inst 2010;102:1413-21
  • Brinton LA, Schwartz L, Spitz MR, et al. Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and lung cancer risk in the NIH-AARP Diet and Health Study Cohort. Cancer Causes Control 2012;23:487-96
  • Clague J, Reynolds P, Sullivan-Halley J, et al. Menopausal hormone therapy does not influence lung cancer risk: results from the California Teachers Study. Cancer Epidemiol Biomarkers Prev 2011;20:560-4
  • Zhou H, Luo MP, Schonthal AH, et al. Effect of reproductive hormones on ovarian epithelial tumors: I. Effect on cell cycle activity. Cancer Biol Ther 2002;1:300-6
  • Chen C, Petitclerc E, Zhou H, et al. Effect of reproductive hormones on ovarian epithelial tumors: II. Effect on angiogenic activity. Cancer Biol Ther 2002;1:307-12
  • Tsilidis KK, Allen NE, Key TJ, et al. Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition. Cancer Causes Control 2011;22:1075-84
  • Morch LS, Lokkegaard E, Andreasen AH, et al. Hormone therapy and ovarian cancer. JAMA 2009;302:298-305
  • Hildebrand JS, Gapstur SM, Feigelson HS, et al. Postmenopausal hormone use and incident ovarian cancer: associations differ by regimen. Int J Cancer 2010;127:2928-35
  • Danforth KN, Tworoger SS, Hecht JL, et al. A prospective study of postmenopausal hormone use and ovarian cancer risk. Br J Cancer 2007;96:151-6
  • Beral V, Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet 2007;369:1703-10
  • Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-37
  • Ouyang P, Michos ED, Karas RH. Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions. J Am Coll Cardiol 2006;47:1741-53
  • Grodstein F, Manson JE, Colditz GA, et al. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med 2000;133:933-41
  • 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
  • Curb JD, Prentice RL, Bray PF, et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med 2006;166:772-80
  • Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465-77
  • Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ 1997;314:796-800
  • Smith NL, Heckbert SR, Lemaitre RN, et al. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA 2004;292:1581-7
  • Hendrix SL, Wassertheil-Smoller S, Johnson KC, et al. Effects of conjugated equine estrogen on stroke in the Women's Health Initiative. Circulation 2006;113:2425-34
  • Renoux C, Dell'aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ 2010;340:c2519
  • Harman SM, Vittinghoff E, Brinton EA, et al. Timing and duration of menopausal hormone treatment may affect cardiovascular outcomes. Am J Med 2011;124:199-205
  • Rosano G, Vitale C, Spoletini I, Fini M. Cardiovascular health in the menopausal woman: impact of the timing of hormone replacement therapy. Climacteric 2012;15:299-305
  • Clarkson TB, Melendez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause 2013;20:342-53
  • Hodis HN, Mack WJ. The timing hypothesis and hormone replacement therapy: a paradigm shift in the primary prevention of coronary heart disease in women. Part 1: comparison of therapeutic efficacy. J Am Geriatr Soc 2013; [Epub ahead of print]
  • Hodis HN, Mack WJ. A “window of opportunity:” the reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent. Brain Res 2011;1379:244-52
  • Prentice RL, Manson JE, Langer RD, et al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 2009;170:12-23
  • Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345:e6409
  • Salpeter SR, Walsh JM, Greyber E, Salpeter EE. Brief report: coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med 2006;21:363-6
  • Davies E, Mangongi NP, Carter CL. Is timing everything? A meeting report of the Society for Women's Health Research roundtable on menopausal hormone therapy. J Womens Health (Larchmt) 2013;22:303-11
  • de Villiers TJ, Gass ML, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Climacteric 2013;16:203-4
  • de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013;16:316-37
  • American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 420, November 2008: hormone therapy and heart disease. Obstet Gynecol 2008;112:1189-92
  • Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007;115:1481-501
  • U.S. Preventive Services Task Force. Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventative Services Task Force. Ann Intern Med 2005;142:855-60
  • Wathen CN, Feig DS, Feightner JW, et al. Hormone replacement therapy for the primary prevention of chronic diseases: recommendation statement from the Canadian Task Force on Preventive Health Care. CMAJ 2004;170:1535-7
  • Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: women's Health Initiative Memory Study. JAMA 2004;291:2947-58
  • Resnick SM, Espeland MA, An Y, et al. Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy. J Clin Endocrinol Metab 2009;94:4152-61

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