The Treatment of Estrogen Deficiency in Women at Risk for Breast Cancer and Survivors of the Disease

  • Richard Santen
  • JoAnn V. Pinkerton
Part of the Endocrine Updates book series (ENDO, volume 8)

Abstract

Many women choose not to take hormone replacement therapy (HRT) after menopause even though medical indications are present (1–5). Among all menopausal women in the United States, only 20–40% ever take HRT (5). Among those given prescriptions, only 65% continue to take the HRT after the first prescription and only 25% for more than three years (6). Many of these women feel that menopause is a natural transition in life and that menopause-associated problems do not require therapy. Others are fearful of complications such as deep venous thrombosis, pulmonary emboli, and stroke or endometrial and breast cancer. For the estimated 2.5 million survivors of breast cancer in the United States, concern about mammary carcinoma risk strongly influences decision making processes regarding HRT.

Keywords

Bone Mineral Density Postmenopausal Woman Vertebral Fracture Estrogen Replacement Therapy Estrogen Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Rabin DS, Cipparrone N, Linn ES, Moen M. Why menopausal women do not want to take hormone replacement therapy. Menopause 1999; 6: 61–67.PubMedCrossRefGoogle Scholar
  2. 2.
    Faulkner DL, Young C, Hutchins D et al. Patient noncompliance with hormone replacement therapy: a nationwide estimate using a large prescription claims database. Menopause 1998; 5: 226–229.PubMedGoogle Scholar
  3. 3.
    Jeffe DB, Freiman M, Fisher EB. Women’s reasons for using postmenopausal hormone replacement therapy: preventative medicine or therapeutic aid? Menopause 1996; 3: 106–116.CrossRefGoogle Scholar
  4. 4.
    Newton KM, LaCroix AZ, Leveille SG et al. The physician’s role in women’s decision making about hormone replacement therapy. Obstet Gynecol 1998; 92: 580–584.PubMedCrossRefGoogle Scholar
  5. 5.
    Keating NL, Cleary PD, Rossi AS, Zaslaysky AM, Ayanian JZ. Use of hormone replacement therapy by postmenopausal women in the United States. Ann Int Med 1999; 130: 545–553.PubMedGoogle Scholar
  6. 6.
    Ettinger B, Li DK, Klein R. Continuation of postmenopausal hormone replacement therapy: comparison of cyclic versus continuous combined schedules. Menopause 1996; 3: 21–25.CrossRefGoogle Scholar
  7. 7.
    Consensus statement: treatment of estrogen deficiency symptoms in women surviving breast cancer. J Clin Endocrinol Metab 1998;83:1993–2000.Google Scholar
  8. 8.
    Santen R, Pritchard K, Burger H, eds. Treatment of estrogen deficiency symptoms in women surviving breast cancer. Obstet Gynecol Sury 1998; 53: S1–83.Google Scholar
  9. 9.
    Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, et al. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation 1987; 75: 1102–1109.PubMedCrossRefGoogle Scholar
  10. 10.
    Sullivan JM, Vander Zwaag R, Hughes JP, Maddock V, Krotez FW, Ramanathan KB. Estrogen replacement and coronary artery disease: Effect on survival in postmenopausal women. Arch Intern Med. 1990; 150: 2557–2562.PubMedCrossRefGoogle Scholar
  11. 11.
    Henderson BE, Paganini-Hill A, Ross RK. Decreased mortality in users of estrogen replacement therapy.Arch Intern Med 1991; 151: 75–78.Google Scholar
  12. 12.
    Wolf PH, Madans JH, Finucane FF, Higgins M, Kleinman JC. Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: evidence from a national cohort. Am J Obstet Gynecol 1991; 164: 489–494.PubMedGoogle Scholar
  13. 13.
    Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prey Med 1991; 20: 47–63.CrossRefGoogle Scholar
  14. 14.
    Grady D, Rubin SM, Petitti DB, Fox CS, Black D, Ettinger B, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992; 117: 1016–1037.PubMedGoogle Scholar
  15. 15.
    Grodstein F, Stampfer MJ. The epidemiology of coronary artery disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995; 38: 199–210.PubMedCrossRefGoogle Scholar
  16. 16.
    Lobo R. Effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. J of Clin Endocrinol and Metab 1991; 73: 925–930.CrossRefGoogle Scholar
  17. 17.
    The Writing Group for the PEPI Trial. Effects of estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995; 274: 199–208.CrossRefGoogle Scholar
  18. 18.
    Clarkson TB, Anthony MS, Klein KP. Hormone replacement therapy and coronary artery atherosclerosis: the monkey model. Br J Obstet Gynaecol 1996;103 (supplement):53–57, discussion 57–58.Google Scholar
  19. 19.
    Tikkanen MJ. Mechanisms of cardiovascular protection by post-menopausal hormone replacement therapy. Cardiovasc Risk Factors 1993; 3: 138–143.Google Scholar
  20. 20.
    Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. New England Journal of Medicine 1999; 340: 1801–11.PubMedCrossRefGoogle Scholar
  21. 21.
    Walsh BW, Li H, Sacks FM. Effects of postmenopausal hormone replacement therapy with oral and transdermal estrogen on high density lipoprotein metabolism. J Lipid Res 1994; 35: 2083–2093.PubMedGoogle Scholar
  22. 22.
    Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B. et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335: 453–461.PubMedCrossRefGoogle Scholar
  23. 23.
    Mosca L, Manson JE, Sutherland SE, Langer RD, Manolio T, Barrett-Connor E. Cardiovascular Disease in women: a statement for health care professionals from the American Heart Association. Circulation 1997; 96: 2468–2482.PubMedCrossRefGoogle Scholar
  24. 24.
    Santen, RJ, Petroni G. Relative versus absolute risk of breast cancer from estrogen replacement therapy. J Clin Endocrinol Metab 1999; 84: 1875–1881.PubMedCrossRefGoogle Scholar
  25. 25.
    Barrett-Connor E. Postmenopausal estrogen and prevention bias. Ann Intern Med 1991; 115: 455–456.PubMedGoogle Scholar
  26. 26.
    Petitti DB. Coronary heart disease and estrogen replacement therapy. Can compliance bias explain the results of observational studies? Ann Epidiol 1994; 4: 115–118.CrossRefGoogle Scholar
  27. 27.
    Matthews KA, Kuller LH, Wing RR, Meilahn EN, Plantinga P. Prior to use of estrogen replacement therapy, are users healthier than nonusers? Am J Epidemiol 1996; 143: 971–978.PubMedCrossRefGoogle Scholar
  28. 28.
    Sturgeon SR, Schairer C, Brinton LA, Pearson T, Hoover RN. Evidence of a healthy estrogen user effect. Epidemiology 1995; 6: 227–231.PubMedCrossRefGoogle Scholar
  29. 29.
    Darling G, Johns J, McCloud P, Davis S. Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997; 337: 595.PubMedCrossRefGoogle Scholar
  30. 30.
    Davidson MH, Testolin LM, Maki KC, von Duvillard S, Drennan KB. Effects of conjugated estrogens alone and combined with pravastatin for management of hypercholesterolemia in postmenopausal women. Arch Intern Med 1997; 157: 118–692.CrossRefGoogle Scholar
  31. 31.
    Jacobs DR Jr, Mebane IL, Bangdiwala SI, Criqui MH, Tyroler HA. HDL cholesterol as a predictor of cardiovascular mortality in men and women: the followup study of the Lipid Research Clinics Prevalence Study. Am J Epidemiol 1990; 131: 32–47.PubMedGoogle Scholar
  32. 32.
    Bass KM, Newschaffer CJ, Klag MJ, Bush U. Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Intern Med 1993153: 2209–16.Google Scholar
  33. 33.
    Grundy SM. Prevention of coronary heart disease through cholesterol reduction. Am Fam Physician 1997; 55: 2250–2258.PubMedGoogle Scholar
  34. 34.
    Holme I. Effects of lipid-lowering therapy on total and coronary mortality. Curr Opin Lipidol 1995; 6: 374–378.PubMedCrossRefGoogle Scholar
  35. 35.
    Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr. Association of levels of lipoprotein Lp (a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74: 758–65.PubMedCrossRefGoogle Scholar
  36. 36.
    Cremer P, Nagel D, Labrot B et al. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study. Eur J Clin Invest 1994; 24: 444–53.PubMedCrossRefGoogle Scholar
  37. 37.
    Scanu AM. Atherogenicity of lipoprotein(a): the debate. Am J Cardiol 1998; 82: 26Q - 33Q.PubMedCrossRefGoogle Scholar
  38. 38.
    Stein EA, Davidson MH, Dobs AS, Schrott H, Dujovne CA, Bays H, Weiss SR, Melino MR, Stepanavage ME, Mitchel YB. Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. The Expanded Dose Simvastatin U.S. Study Group. Am J Cardiol 1998; 82: 311–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Downs JR, Clearfield M, Weiss DO et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA 1998; 279: 1615–1622.PubMedCrossRefGoogle Scholar
  40. 40.
    Love RR, Wiebe DA, Feyzi JM, Newcomb PA, Chappell RJ. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 6 years of treatment. J Natl Cancer Inst 1994; 86: 1534–1539.PubMedCrossRefGoogle Scholar
  41. 41.
    Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J, Davey J. Interim analysis of the incidence of breast cancer in the royal Marsden Hospital tamoxifen randomized chemoprevention trial. The Lancet 1998; 353: 98–101.Google Scholar
  42. 42.
    Grey A, Stapleton J, Evans M et al. The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women. J Clin Endocrin Metab 1995; 80: 31.CrossRefGoogle Scholar
  43. 43.
    Fisher B, Costantino JP, Wickerham L, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90: 1371–88PubMedCrossRefGoogle Scholar
  44. 44.
    Collaborative group on hormonal factors in breast cancer. Breast Cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiologic studies of 52, 705 women with breast cancer and 108411 women without breast cancer Lancet 1997; 350: 1047–1059.Google Scholar
  45. 45.
    Bjarnason NH, Haarbo J, Byrjalsen I, Kauffman RF, Christiansen C. Raloxifene inhibits aortic accumulation of cholesterol in ovariectomized, cholesterol-fed rabbits. Circulation 1997; 96: 1964–1969.PubMedCrossRefGoogle Scholar
  46. 46.
    Delmas PD, Bjarnason NH, Mitlak BH, Ravoux A-C, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997; 337: 1641–1647.PubMedCrossRefGoogle Scholar
  47. 47.
    Draper MW, Flowers DE, Huster WJ, Neild JA, Harper KD, Arnaud C. A controlled trial of raloxifene (LY139481) HC1: impact on bone turnover and serum lipid profile in healthy postmenopausal women. J Bone Miner Res 1996; 11: 835–842.PubMedCrossRefGoogle Scholar
  48. 48.
    Clarkson TB, Anthony MS, Jerome CP. Lack of effect of Raloxifene on coronary artery atherosclerosis of postmenopausal monkeys. J Clin Endocrinol Metab 1998; 83: 721–726.PubMedCrossRefGoogle Scholar
  49. 49.
    Cline MJ, Paschold JC, Anthony MS, Obasanjo IO, Adams MR. Effects of hormonal therapies and dietary soy phytoestrogens on vaginal cytology in surgically menopausal macaques. Fertil Steril 1996; 65: 1031–1035.PubMedGoogle Scholar
  50. 50.
    Murkies AL, Wilcox G, Davis SR. Clinical Review 92. Phytoestrogens. J Clin Endocrinol Metab 1998; 83: 297–303.CrossRefGoogle Scholar
  51. 51.
    Shimizu H, Ross RK, Bernstein L, Yatani R, Hendersen BE, Nack TM. Cancers of the Prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 1991; 63: 963–966.PubMedCrossRefGoogle Scholar
  52. 52.
    Hirayama T. A Large scale cohort study on cancer risks by diet-with special reference to the risk reducing effects of green-yellow vegetable consumption. In: Hayashi Y, ed. Diet Nutrition Cancer. Tokyo: Japanese Scientific Society Press, 1986: 41–43.Google Scholar
  53. 53.
    Lee HP, Gourley L, Duffy SW. Dietary effects on breast-cancer risk in Singapore. Lancet 1991; 337: 1197–1200.PubMedCrossRefGoogle Scholar
  54. 54.
    Adlercreutz H. Western diet and western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest 1990;50(Suppl): 210: 3–23.Google Scholar
  55. 55.
    Agnusdei D, Adami S, Cervetti R et al. Effects of ipriflavone on bone mass and calcium metagolism in postmenopausal osteoporosis. Bone Miner 1992; 19: S43 - S48.PubMedCrossRefGoogle Scholar
  56. 56.
    Anthony MS. Clarkson TB. Bullock BC. Wagner JD. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler Thromb Vasc Biol 1997; 17: 2524–31.PubMedCrossRefGoogle Scholar
  57. 57.
    Wagner J, Cefalu W, Anthony M, Litwak K, Zhang L, Clarkson T. Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys. Metabolism 1997; 46: 698–705.PubMedCrossRefGoogle Scholar
  58. 58.
    Clarkson TB. Anthony MS. Williams JK. Honore EK. Cline JM. The potential of soybean phytoestrogens for postmenopausal hormone replacement therapy. Proc Society for Experimental Biol Med 1998; 217: 365–8.Google Scholar
  59. 59.
    Honore EK, Williams JK, Anthony MS, Clarkson TB. Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques. Fertil Steril 1997; 67: 148–154.PubMedCrossRefGoogle Scholar
  60. 60.
    Anderson J, Johnstone B, Cook-Newell M. Meta-analysis of the effects of soy protein intake on serum lipids. NEJM 1995; 333: 276–282.PubMedCrossRefGoogle Scholar
  61. 61.
    Nestel PJ, Pomeroy S, Kay S, Komesaroff P, Behrsing J, Cameron JD, West L.. Isoflavones from Red Clover improve systemic arterial compliance but not plasma lipids in menopausal women. J Clin Endocrinol Metab 1999; 84: 895–898.PubMedCrossRefGoogle Scholar
  62. 62.
    Sullivan JM. Atherosclerosis and estrogen replacement therapy. Int J Fertil Menopausal Studies 1994; 39 (suppl 1): 28–35.Google Scholar
  63. 63.
    Sidney S, Petitti DB, Quesenberry CP. Myocardial infarction and the use of estrogen and estrogen-progestogen in postmenopausal women. Ann of Intern Med 1997; 127: 501–508.Google Scholar
  64. 64.
    Grodstein F, Stampfer MJ, Colditz GA, Willett WC, Manson JE, Joffe M, et al. Postmenopausal hormone therapy and mortality. New Eng J Med 1997; 336: 1769–1775.PubMedCrossRefGoogle Scholar
  65. 65.
    Sullivan JM, Vander Zwaag R, Hughes JP, Maddock V, Kroetz FW, Ramanathan KB, et al. Estrogen replacement and coronary artery disease: effect on survival in postmenopausal women. Arch Int Med 1990; 150: 2557–2562.CrossRefGoogle Scholar
  66. 66.
    Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–613.PubMedCrossRefGoogle Scholar
  67. 67.
    Herrington DM. The HERS trial results: Paradigms lost? Perspective: Annals of Internal Medicine 131: 463–466, 1999.Google Scholar
  68. 68.
    Register TC. Adams MR. Golden DL. Clarkson TB. Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys. Arterioscler Thromb Vasc Biol 1998; 18: 1164–71.PubMedCrossRefGoogle Scholar
  69. 69.
    Sullivan JM, El-Zeky F, Zwaag R, Ramanathan KB. Effect on Survival of estrogen replacement therapy after coronary artery bypass grafting. Am J Cardiol 1997; 79: 847–850.PubMedCrossRefGoogle Scholar
  70. 70.
    O’Brien JE, Peterson ED, Keeler GP, Berdan LG, Ohlkman EM, Faxon DP, Jakobs AK, Topol EJ, Califf RM. Relation between estrogen replacement therapy and restenosis after percutaneous coronary interventions. J Am Coll Cardiol 1996; 28: 1111–1118.PubMedCrossRefGoogle Scholar
  71. 71.
    Jonas HA, Kronmal RA, Psaty BM et al. Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study. Ann Epidemiol 1996; 6: 314–323.PubMedCrossRefGoogle Scholar
  72. 72.
    Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian simvastatin survival study. Arch Intern Med 1996; 156: 2085–2092.PubMedCrossRefGoogle Scholar
  73. 73.
    Pedersen TR. Olsson AG. Faergeman O. Kjekshus J. Wedel H. Berg K. Wilhelmsen L. Haghfelt T. Thorgeirsson G. Pyorala K. Miettinen T. Christophersen B. Tobert JA. MuslinerTA, Cook TJ. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S) Circulation 1998; 97: 1453–60.PubMedGoogle Scholar
  74. 74.
    Knopp RH. Drug treatment of lipid disorders. New England J Medicine 1999; 341: 498–511.CrossRefGoogle Scholar
  75. 75.
    Dawson-Hughes B, Harris S, Krall E, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337: 670–676.PubMedCrossRefGoogle Scholar
  76. 76.
    Friedlander A, Genant H, Sadowsky S, et al. A two-year program of aerobics and weight training enhances bone mineral density of your women. J Bone Min Res 1995; 10: 574–585.CrossRefGoogle Scholar
  77. 77.
    Kerr D, Morton A, Dick I, Prince R. Exercise effects on bone mass in postmenopausal women are site-specific and load dependent. J Bone Miner Res 1996; 11: 218–225.PubMedCrossRefGoogle Scholar
  78. 78.
    Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R. The effect of calcium supplementation on the circadian rhythm of bone resorption. J Clin Endocrinol Metab 1994; 79: 730–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Eastell R. Drug therapy: treatment of postmenopausal osteoporosis. N Engl J Med 1998; 338: 736–746.PubMedCrossRefGoogle Scholar
  80. 79a.
    Physcian’s Guide to Prevention and Treatment of Osteoporosis.. Washington, DC. National Osteoporosis Foundation. 1998.Google Scholar
  81. 80.
    The Writing Group for the PEPI. Effects of hormone replacement therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1996; 276: 1389–1396.CrossRefGoogle Scholar
  82. 81.
    Ettinger B, Grady D. The waning effect of postmenopausal estrogen therapy on osteoporosis. N Engl J Med 1993; 329: 1192–1193.PubMedCrossRefGoogle Scholar
  83. 82.
    Recker RR, Davies KM, Heaney RP. Bone saving effects of low dose continuous estrogen/progestin with calcium and vitamin D in elderly women: a randomized, controlled trial. Ann Int Med 1999; 130: 897–906.PubMedGoogle Scholar
  84. 83.
    Lindsay R, Bush TL, Grady D, Speroff 1, Lobo RA. Therapeutic controversy: estrogen replacement in menopause. J Clin Endocrinol Metab 1996; 81: 3829–3838.PubMedCrossRefGoogle Scholar
  85. 84.
    Cauley JA, Seeley DG, Ensrud K, et al. Estrogen replacement and fractures in older women. Ann Intern Med 1995; 122: 9–16.PubMedGoogle Scholar
  86. 85.
    Felson DT, Zhang Y, Hannan MT et al. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993; 329: 1141–1146.PubMedCrossRefGoogle Scholar
  87. 86.
    Genant HK, Lucas J, Weiss S, Akin M, Emkey R, McNaney-Flint H, et al. for the Estratab/Osteoporosis Study Group. Low-dose esterified estrogen therapy. Effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Arch Intern Med 1997; 157: 2609–15.PubMedCrossRefGoogle Scholar
  88. 87.
    Ettinger B, Genant HK, Cann CE. Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium. Ann Intern Med 1987; 106: 40–5.PubMedGoogle Scholar
  89. 88.
    Schneider DL, Barrett-Connor EL, Morton DJ Timing of postmenopausal estrogen for optimal bone mineral density. The Ranco Bernado Study. JAMA 1997; 277: 5437.Google Scholar
  90. 89.
    Kiel DP, Felson DT, Anderson JJ, Wilson PWF, Moskowitz MA. Hip fracture and the use of estrogen in postmenopausal women: the Framingham Study. N Engl J Med 1987; 317: 1169–74.PubMedCrossRefGoogle Scholar
  91. 90.
    Maxim P, Ettinger B, Spitalny GM. Fracture protection provided by long-term estrogen treatment. Osteoporos Int 1995; 5: 23–9.PubMedCrossRefGoogle Scholar
  92. 91.
    Paganini-Hill A, Ross RK, Gerkins VR, Henderson BE, Arthur M, Mack TM. Menopausal estrogen therapy and hip fractures. Ann Intern Med 1981; 95: 28–31.PubMedGoogle Scholar
  93. 92.
    Lufkin EG, Wanner HW, O’Fallon WM, Hodgson SF, Kotowicz MA, Lane AW et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992117: 1–91.Google Scholar
  94. 93.
    Col NF, Eckman MH, Pauker SG, Goldberg RJ, Ross EM, On RK, Wong JB. Patient specific decisions about hormone replacement therapy in postmenopausal women JAMA 1997; 277: 1140–1147.Google Scholar
  95. 94.
    Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR. Estrogen replacement therapy and fractures in older women: Study of Osteoporosis Fractures Research Group. Ann Intern Med 1995; 122: 9–16.PubMedGoogle Scholar
  96. 95.
    Hosking D, Chilvers CED, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med 1998; 338: 485–492.PubMedCrossRefGoogle Scholar
  97. 96.
    Chesnut C, McClung M, Ensrud K, et al. Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med 1995; 99: 144–152.PubMedCrossRefGoogle Scholar
  98. 97.
    Ravn P, Bidstrup M, Wasnich RD et al. Alendronate and Estrogen-Progestin in the long term prevention of bone loss: four year results from the early postmenopausal intervention cohort study. A randomized, controlled trial. Annals of Internal Medicine 1999131: 935–942.Google Scholar
  99. 98.
    Bone HG, Downs RW, Tucci JR, et al. Dose-response relationships for alendronate treatment in osteoporotic elderly women. J Clin Endocrinoland Metabol 1997; 82: 265–274.CrossRefGoogle Scholar
  100. 98a.
    Lindsay R, Cosman F, Lobo R et al. Addition of alendronate to ongoing hormone replacement therapy in treatment of osteoporosis: a randomized controlled clinical trial. J Clin Endocrinol Metab 1999; 84: 3076–3081.PubMedCrossRefGoogle Scholar
  101. 99.
    Liberman UA, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437.PubMedCrossRefGoogle Scholar
  102. 99a.
    Ensrud KE, Black DM, Palermo L, Bauer DC, Barrett-Connor E, Quandt SA, et al. Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial. Arch Int Med 1997; 157: 2617–24.CrossRefGoogle Scholar
  103. 100.
    Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. Results from the fracture intervention trial. JAMA 1998; 280: 2077.Google Scholar
  104. 100a.
    Harris ST, Watts NB, Genant HK et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 1999; 282: 1344–1352.PubMedCrossRefGoogle Scholar
  105. 101.
    Reginster J, Deroisy R, Lecart M, et al. A double-blind, placebo-controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss. Am J Med 1995; 98: 452–8.PubMedCrossRefGoogle Scholar
  106. 102.
    Ellerington M, Hillard T, Whitcroft S, et al. Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis. Calcif Tissue Int 1996; 59: 6–11.PubMedCrossRefGoogle Scholar
  107. 103.
    Overgaard K, Hansen M, Jensen S, Christiansen C. Effect of calcitonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study. Br Med J 1992; 305: 556–561.CrossRefGoogle Scholar
  108. 104.
    Chesnut C, Baylink DJ, Doyle D, Genant G, Harris S, Kiel DP, LeBoff M, Stock JL, Gimona A, Andriano K, Richardson P. Salmon-Calcitonin Nasal Spray prevents vertebral fractures in established osteoporosis. Further interim results of the PROOF study. European Congress on Osteoporosis, Abstracts. Osteoporo hit 1999; 8 (suppl 13): 13.Google Scholar
  109. 105.
    Powles TJ, Hickish T, Kanis JA et al. Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in health premenopausal and postmenopausal women. J Clin Oncol 1996; 14: 78–84.PubMedGoogle Scholar
  110. 106.
    Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR. 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) JAMA 1999; 282 (7): 637–45.PubMedGoogle Scholar
  111. 107.
    Seeman, E. Osteoporosis: Trials and Tribulations. [Proceedings of a Symposium: Advances in the Epidemiology, Prevention, and Treatment of Osteoporosis and Fractures] Am J of Med 1997;103(1 S)Supplement 74S–87S.Google Scholar
  112. 108.
    Watts NB. Postmenopausal osteoporosis. Obstetrical and Gynecological Survey 1999; 54: 532–538.PubMedCrossRefGoogle Scholar
  113. 109.
    Jordan VC, Glusman JE, Eckert S et al. Raloxifene reduces incident primary breast cancer: integrated data from multi-center, double blind, placebo controlled, randomized trials in postmenopausal women. Breast Cancer Research and Treatment 21:227 (abstract) 1998 Proceedings of the San Antonio Breast Cancer Symposium.Google Scholar
  114. 109a.
    Cummings SR, Eckert S, Krueger KA, Grady D et al. The Effect of raloxifene on risk of breast cancer in postmenopausal women. Results from MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999; 281: 2189–2197.PubMedCrossRefGoogle Scholar
  115. 110.
    Roe EB, Sanchez SD, del Puerto GA, Pierini E, Bacchetti P, Cann CE, Arnaud CD. Treatment of postmenopausal osteoporosis with human parathyroid hormone 1–34 and estrogen. Proceedings of the 81st Annual meeting of the Endocrine Society S-63–1, pg 59, 1999.Google Scholar
  116. 111.
    Mundy G, Garrett R,Hams S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone formation in vitro and in rodents by statins Science 1999; 286: 1946–1949.Google Scholar
  117. 112.
    Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Harris F, Duong T, Cummings SR. Statin use, bone mass and fracture: an analysis of two prospective studies. J. Bone and Mineral Res 1999;14: supplement 1, 1188, (Abstract)Google Scholar
  118. 113.
    Loprinzi C, Abu-Ghazaleh S, Sloan J, et al. Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer. J Clin Oncol 1997; 15: 969–973.PubMedGoogle Scholar
  119. 114.
    Nachtigall LE. Comparative study: Replens versus local estrogen in menopausal women. Fertil Steril 1994; 61: 178–180.PubMedGoogle Scholar
  120. 115.
    Handa V, Bachus K, Johnston W, et al. Vaginal administration of low-dose conjugated estrogens: systemic absorption and effects on the endometrium. Obstet Gynecol 1994; 84: 215.PubMedGoogle Scholar
  121. 116.
    Ayton R, Darling G, Murkies A, et al. A comparative study of safety and efficacy of continuous low dose oestradiol released from a vaginal ring compared with conjugated equine oestrogen vaginal cream in the treatment of postmenopausal urogenital atrophy. Br J Obstet Gynaecol 1996; 103: 351–358.PubMedCrossRefGoogle Scholar
  122. 117.
    Henriksson L, Stjernquist M, Boquist L, Cedergren I, Selinus I. A one-year multicenter study of efficacy and safety of a continuous, low-dose, estradiolreleasing vaginal ring (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Am J Obstet Gynecol 1996174: 85–92.Google Scholar
  123. 118.
    Eriksen BC. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women Am J Obstet Gynecol 1999; 180: 1072–1079.Google Scholar
  124. 119.
    Santen RJ, Wisniewski L, Ropka M, Pinkerton JV, Demers L, Connaway M, Oerter-Klein K. Treatment of urogenital atrophy. Proceedings of the North American Menopuase Society 1998; Abstract number 98. 121.Google Scholar
  125. 120.
    Barton DL, Loprinzi CL, Quella SK, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16: 495–500.Google Scholar
  126. 121.
    Goldberg R, Loprinzi C, OTallon J, et al. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes. 1994;J Clin Oncol 12: 155.Google Scholar
  127. 122.
    Laufer LR, Erlik Y, Meldrum DR, Judd HL. Effect of clonidine on hot flashes in postmenopausal women. Obstet Gynecol 1982; 60: 583–586.PubMedGoogle Scholar
  128. 123.
    Loprinzi CL, Michalak JC, Quella SK, O“Fallon JR, Hatfield A, Nelimark RA, Dose AM, Fischer T, Johnson C, Klatt NE, Bate WW, Respond RM and Oesterlipg JE. Megestrol acetate for the prevention of hot flashes. N Engl J Med 1994; 331: 347–352.PubMedCrossRefGoogle Scholar
  129. 124.
    Loprinzi C, Pisansky T, Fonseca R, Sloan J, et al. Pilot evaluation of vanlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. J Clinical Oncology 1998; 16: 2377–812.Google Scholar
  130. 125.
    Lien E. Hormone therapy and phytoestrogens. J Clin Pharm and Ther 1996; 2: 101–111CrossRefGoogle Scholar
  131. 126.
    Hirata JD. Swiersz LM. Zell B. Small R. Ettinger B. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997; 68: 981–6.PubMedCrossRefGoogle Scholar
  132. 127.
    Kowall NW. Alzheimer disease 1999: a status report. Alzheimer Disease and Associated Disorders 1999;13 Suppl 1: S11–16.Google Scholar
  133. 128.
    Birge SJ. The role of estrogen in the treatment of Alzheimer’s disease. Neurology 1997; 48 (5 suppl 7): S36 - S41.PubMedCrossRefGoogle Scholar
  134. 129.
    Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA 1998; 279: 688–695.PubMedCrossRefGoogle Scholar
  135. 130.
    Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Australian and New Zealand Journal of Ophthalmology 1997; 25 (suppl 1): S13–15.PubMedCrossRefGoogle Scholar
  136. 131.
    Grodstein F, Martinez ME, Platz EA, Giovannucci E, Colditz GA, Kautzky M, Fuchs C, Stampfer MJ. Postmenopausal hormone use and risk for colorectal cancer and adenoma. Ann Intern Med 1998; 128: 705–712.PubMedGoogle Scholar
  137. 132.
    Paganini-Hill A. The benefits of estrogen replacement therapy on oral health. Arch Intern Med 1995; 155: 2325–2329.PubMedCrossRefGoogle Scholar
  138. 133.
    Felson DT, Nevitt MC. The effects of estrogen and osteoarthritis. Curr Opin Rheumatol 1998; 10: 269–272.PubMedCrossRefGoogle Scholar
  139. 134.
    Colditz GA, Hankinson SE, Hunter DJ, Willet WC, Manson JE, Stampfer MJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995; 332: 1589–1593.PubMedCrossRefGoogle Scholar
  140. 135.
    Daly E, Vessey MP, Hawkins, MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996; 348: 977–980.PubMedCrossRefGoogle Scholar
  141. 136.
    Petitti DB, Sidney S, Perlman JA. Increased risk of cholecystectomy in users of supplemental estrogen. Gastroenterol 1988; 94: 91–5.Google Scholar
  142. 137.
    Nakahara K, Kuriyama M, Sonoda Y, Yoshidome H, Nakagawa H, Fujiyama J, Higuchi I, Osame M. Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysical and biochemical study. Toxicol Appl Pharmacol 1998; 152: 99–106.PubMedCrossRefGoogle Scholar
  143. 138.
    Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P. Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 1997; 57: 3890–4.PubMedGoogle Scholar
  144. 139.
    De Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang DD. Esophagitis associated with the use of Alendronate. NEJM 1996; 335: 1016–1021.PubMedCrossRefGoogle Scholar
  145. 140.
    Ettinger B, Pressman A, Schein J. Clinic visits and hospital admissions for care of acid-related upper gastrointestinal disorders in women using alendronate for osteoporosis. Am J Man Care 1998; 4; 1377–1382.Google Scholar
  146. 140a.
    Nevitt MC, Thompson DE, Black DM, Rubin SR, Ensrud KE, Yates AJ, Cummings SR.. Effect of alendronate on limited activity days and bed disability days caused by back pain in postmenopausal women with existing vertebral fractures. Arch Int Med 2000; 160: 77–85.CrossRefGoogle Scholar
  147. 141.
    Gennari C, Agnusdei D, Camporeale A. Use of calcitonin in the treatment of bone pain associated with osteoporosis. Calcif Tissue Int 1991;49:Suppl 2: S9 - S13.Google Scholar
  148. 142.
    Delete same as 109a but has different authors. Need to check correct authors. Cummings SR, Eckert S, Krueger KA, Grady d 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.Google Scholar
  149. 143.
    Ragaz J, Coldman A. Survival impact on competing causes of mortality in breast cancer survivors. J Clin Oncol 1998; 16: 2018–2024.PubMedGoogle Scholar
  150. 144.
    Tyler V. What pharmacists should know about herbal remedies. J Am Pharm Assoc 1996 NS36:29–37.Google Scholar
  151. 145.
    Koff R. Herbal hepatotoxicity: revisiting a dangerous alternative. JAMA 1995 273: 502–503.PubMedCrossRefGoogle Scholar
  152. 146.
    Sheikh N, Philen, RM, Love, LA. Chaparral-associated hepatotoxicity. Arch of Int Med 1997; 157: 913–9.CrossRefGoogle Scholar
  153. 147.
    Loprinzi CL, Pisansky TM, Fonseca R, Sloan JA, Zahasky KM, Quella SK, Novotny PJ, Rummans TA, Dumesic DA, Perez EA. Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors. Journal of Clinical Oncology. 1998; 16: 2377–81.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Richard Santen
    • 1
  • JoAnn V. Pinkerton
    • 1
  1. 1.The Department of Medicine, Division of Endocrinology, and The Department of Obstetrics/ Gynecology and the Women’s PlaceUniversity of Virginia Health SystemCharlottesvilleUSA

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