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REFERENCES 1 Jensen EV, Jacobsen HI. Basic guides to the mechanism of estrogen action. Recent Prog Horm Res 1962;18:387–414. 2 Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science 1986;231(4742):1150–4. 3 Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J-Å. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996;93(12):5925–30. 4 Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett 1996;392:49–53. 5 Enmark E, Pelto-Huikko M, Grandien K, et al. Human estrogen receptor beta - gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997;82(12):4258–65. 6 Tremblay GB, Tremblay A, Copeland NG, et al. Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol Endocrinol 1997;11(3):353–65. 7 Ogawa S, Inoue S, Watanabe T, et al. The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro. Biochem Biophys Res Commun 1998;243(1):122–6. 8 Leygue E, Dotzlaw H, Lu B, Glor C, Watson PH, Murphy LC. Estrogen receptor beta: mine is longer than yours? J Clin Endocrinol Metab 1998;83(10):3754–5. 9 Chu S, Fuller PJ. Identification of a splice variant of the rat estrogen receptor beta gene. Mol Cell Endocrinol 1997;132(1-2):195–9. 94 10 Petersen DN, Tkalcevic GT, Koza-Taylor PH, Turi TG, Brown TA. Identification of estrogen receptor beta 2, a functional variant of estrogen receptor beta expressed in normal rat tissues. Endocrinology 1998;139(3):1082–92. 11 Moore JT, McKee DD, Slentz-Kesler K, et al. Cloning and characterization of human estrogen receptor b isoforms. Biochem Biophys Res Commun 1998;247(1):75–8. 12 Ogawa S, Inoue S, Watanabe T, et al. Molecular cloning and characterization of human estrogen receptor beta cx: a potential inhibitor of estrogen action in human. Nucleic Acids Res 1998;26(15):3505–12. 13 Zhang QX, Hilsenbeck SG, Fuqua SA, Borg A. Multiple splicing variants of the estrogen receptor are present in individual human breast tumors. J Steroid Biochem Mol Biol 1996;59(3–4):251–60. 14 Friend KE, Resnick EM, Ang LW, Shupnik MA. Specific modulation of estrogen receptor mRNA isoforms in rat pituitary throughout the estrous cycle and in response to steroid hormones. Mol Cell Endocrinol 1997;131(2):147–55. 15 Karas RH, Hodgin JB, Kwoun M, et al. Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc Natl Acad Sci USA 1999;96(26):15133–6. 16 Couse JF, Hewitt CS, Bunch DO, et al. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science 1999;286(5448):2328–31. 17 Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994;63:451–86. 18 Giguère V. Orphan nuclear receptors: from gene to function. Endocr Rev 1999;20(5):689–725.
19 Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 199;83(6): 835–9. 20 Shibata H, Spencer TE, Onate SA, et al. Role of coactivators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent Prog Horm Res 1997;52:141–5. 21 Berry M, Metzger D, Chambon P. Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J 1990;9(9):2811–8. 22 McInerney EM, Tsai MJ, O’Malley BW, Katzenellenbogen BS. Analysis of estrogen receptor transcriptional enhancement by a nuclear hormone receptor coactivator. Proc Natl Acad Sci USA 1996;93(19):10069–73. 23 Webb P, Nguyen P, Shinsako J, et al. Estrogen receptor activation function 1 works by binding p160 coactivator proteins. Mol Endocrinol 1998;12(10):1605–18. 24 Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J-Å, Nilsson S. Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmacol 1998;54(1):105–12. 25 McInerney EM, Katzenellenbogen BS. Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcription activation. J Biol Chem 1996;271(39):24172–8. 26 McInerney EM, Weis KE, Sun J, Mosselman S, Katzenellenbogen BS. Transcription activation by the human estrogen receptor subtype beta (ER beta) studied with ER beta and ER alpha receptor chimeras. Endocrinology 1998;139(11):4513–22. 27 Mak HY, Hoare S, Henttu PM, Parker MG. Molecular determinants of the estrogen receptor-coactivator interface. Mol Cell Biol 1999;19(5):3895–903. 28 Brzozowski AM, Pike AC, Dauter Z, et al. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 1997;389(6652): 753–8. 29 Shiau AK, Barstad D, Loria PM, et al. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 1998;95(7):927–37. 30 Pike AC, Brzozowski AM, Hubbard RE, et al. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO J 1999;18(17):4608–18. 31 McDonnell DP, Clemm DL, Hermann T, Goldman ME, Pike JW. Analysis of estrogen receptor function in vitro reveals three distinct classes of antiestrogens. Mol Endocrinol 1995;9(6):659–69. 32 Paige LA, Christensen DJ, Gron H. et al. Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci USA 1999;96(7):3999–4004. 33 Katzenellenbogen JA, O’Malley BW, Katzenellenbogen BS. Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promoterspecific action of these hormones. Mol Endocrinol 1996;10(2):119–31. 34 Galien R, Garcia T. Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-kappaB site. Nucleic Acids Res 1997;25(12):2424–9. 35 Montano MM, Jaiswal AK, Katzenellenbogen BS. Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. J Biol Chem 1998;273(39):25443–9. 36 Webb P, Nguyen P, Valentine C, et al. The estrogen receptor enhances AP-1 activity by two distinct mechanisms with different requirements for receptor transactivation functions. Mol Endocrinol 1999;13(10):1672–85. 37 Qin C, Singh P, Safe S. Transcriptional activation of insulin-like growth factor-binding protein-4 by 17 beta-estradiol in MCF-7 cells: role of estrogen receptor-SP1 complexes. Endocrinology 1999;140(6):2501–8. 38 Saville B, Wormke M, Wang F, et al. Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements. J Biol Chem 2000;275(8):5379–87. 39 Paech K, Webb P, Kuiper GGJM, et al. Differential ligand activation of estrogen receptors ER alpha and ER beta at AP1 sites. Science 1997;277(5331):1508–10. 95
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National Heart, Lung, and Blood Ins
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CHAIRS AND EDITORS Chair and Editor
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Anne McTiernan, M.D., Ph.D. Associa
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Lenore Manderson, Ph.D. Director an
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Michael Mendelsohn, M.D. Director,
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TABLE OF CONTENTS Preface XIII 1 Ex
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PREFACE Women’s health and menopa
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CHAPTER 1: EXECUTIVE SUMMARY Nanett
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TABLE 1-1 Evidence Categories Evide
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TABLE 1-2 (continued) Possible Bene
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symptom measures, cultural factors,
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5. PHYSIOLOGICAL ROLE OF ESTROGEN A
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The atherogenic risk profile of old
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• Hormone replacement therapy: Fi
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tion of the remaining ridge in area
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9.3.1 Interventions • In many cas
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Parkinson’s disease, no overall p
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TABLE 1-3 (continued) Sexuality •
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CHAPTER 2: THE MENOPAUSE AND AGING
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oped and are less prepared to addre
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FIGURE 2-4 Diabetes Mellitus. Estim
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Sarcopenia, defined as reduced musc
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Perimenopause WHO The term “perim
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decrease about 2 years before the F
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4.3 Menstrually Defined Menopausal
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to be under stress and to hold part
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21 Brincat MP. Hormone replacement
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62 Orentreich N, Brind JL, Rizer RL
Page 59 and 60: CHAPTER 3: SYMPTOMS AND THE MENOPAU
Page 61 and 62: women who may have reached natural
Page 63 and 64: numb-tingling feelings, headaches,
Page 65 and 66: (47 percent), problems sleeping (39
Page 67 and 68: FIGURE 3-2 Proportion of Women Both
Page 69 and 70: tomized hypogonadotropic women expe
Page 71 and 72: 5.1 Exercise It has been suggested
Page 73 and 74: to consume 20-150 mg/day of isoflav
Page 75 and 76: REFERENCES 1 Stewart AL, Hays RD, W
Page 77 and 78: 48 Avis NE, Crawford SL, McKinlay S
Page 79: 92 Albertazzi P, Pansini F, Bonacco
Page 82 and 83: Hällström wrote that the psycholo
Page 84 and 85: countries. Perhaps, as the authors
Page 86 and 87: Beyene used a systematic ethnograph
Page 88 and 89: ange of variables, such as genetic
Page 90 and 91: REFERENCES 1 Gannon L, Ekstrom B. A
Page 92 and 93: 47 George T. Women in a south India
Page 94 and 95: 9. Estrogen and inhibins produced b
Page 96 and 97: HRT) display tissue-selective estro
Page 98 and 99: a partial agonist. In contrast, wit
Page 100 and 101: 3. UROGENITAL TRACT ERα and ERβ a
Page 102 and 103: 4. BONE: DEVELOPMENT AND HOMEOSTASI
Page 104 and 105: in response to estrogen. 106,105 In
Page 106 and 107: lation of sleep, motor behavior, an
Page 108 and 109: 7. HORMONE REPLACEMENT THERAPY: TRA
Page 112 and 113: 40 Power RF, Mani SK, Codina J, Con
Page 114 and 115: 83 Oursler MJ, Pederson L, Fitzpatr
Page 116 and 117: 125 Gabrielsson BG, Carmignac DF, F
Page 118 and 119: 169 Renier MA, Vereecken A, Buytaer
Page 120 and 121: FIGURE 6-1 Structural features of E
Page 122 and 123: ound, the conformation of the recep
Page 124 and 125: with extremely potent estrogenic ac
Page 126 and 127: Its potency as an antiestrogen was
Page 128 and 129: The observation that the degree of
Page 130 and 131: findings were remarkable because a
Page 132 and 133: Recently, the use of phage display
Page 134 and 135: 20 Crawley G. Non steroidal estroge
Page 136 and 137: 65 Qu Q, Zheng H, Dahllund J, et al
Page 138 and 139: in their survey of postmenopausal w
Page 140 and 141: where over half the world’s popul
Page 142 and 143: The Danish study of Koster and Gard
Page 144 and 145: Many studies of sexual interest in
Page 146 and 147: 7. ASSESSING SEXUAL ACTIVITY Clinic
Page 148 and 149: None of these studies evaluated the
Page 150 and 151: estrogen-androgen group during the
Page 152 and 153: REFERENCES 1 Sarrel PM, Whitehead M
Page 154 and 155: 52 Utian WH. The true clinical feat
Page 156 and 157: 140
Page 158 and 159: outes of administration and differe
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FIGURE 8-2 Change in Age-Adjusted D
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fied as overweight or obese. 32 The
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TABLE 8-1 148 Guide to Risk Reducti
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TABLE 8-1 (continued) 150 Recommend
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TABLE 8-1 (continued) 152 Recommend
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Interesting differences in atherosc
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similar effects in both patients wi
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a lowering of triglycerides, 140 an
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may account for a substantial propo
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associated with an independent prot
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eases preoperatively. Quality of li
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excess risk of 6-18 per 10,000 per
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REFERENCES 1 NHLBI Morbidity and Mo
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36 Samaras K, Hayward CS, Sullivan
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79 Collins P, Rosano GM, Jiang C, L
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121 Mäkelä S, Savolainen H, Aavik
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162 Clarke S, Kelleher H, Lloyd-Jon
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201 Rahimtoola SH, Bennett AJ, Grun
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243 Varas-Lorenzo C, Garcia-Rodriqu
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7. A connection between menopausal
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3. PATHOGENESIS OF FRACTURE Fractur
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Diagnosis of osteoporosis according
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density and has a favorable effect
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How should this information be inco
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emergence of proved treatment alter
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Data on the relation between skelet
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REFERENCES 1 Osteoporosis Preventio
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42 Gluer CC. Quantitative ultrasoun
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85 Ettinger B, Pressman A, Silver P
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130 Jeffcoat MK, Lewis CE, Reddy M,
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1. INTRODUCTION Perimenopausal wome
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for breast cancer are at increased
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findings on biopsy in women with an
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thra. Patients typically describe l
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Biofeedback: Used in conjunction wi
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There has been one systematic revie
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ence in pelvic organ prolapse. The
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21 Ferenczy A. Endometrial carcinom
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65 Wyman JF, Fantl JA, McClish DK,
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222
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1. INTRODUCTION Worldwide, breast c
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difficult to compare because of com
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Although HRT has been related to an
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cyclic use and 2.9 (95 percent CI 2
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TABLE 11-3 Selected Studies on Horm
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TABLE 11-3 (continued) Thus, a stro
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TABLE 11-4 236 Cohort Studies on Ho
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TABLE 11-5 238 Case-Control Studies
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TABLE 11-5 (continued) 240 Adjustme
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When the same women in NSABP were r
Page 260 and 261:
REFERENCES 1 Pisani P, Parkin DM, B
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47 Day NE. Epidemiology: the role o
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93 Rodriguez C, Patel AV, Calle EE,
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139 Parazzini F, La Vecchia C, Negr
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1. INTRODUCTION Menopause is associ
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inverse relation with nonverbal mem
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ease decreased significantly with i
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of households selected to be repres
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standard antipsychotic drugs increa
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5. FUTURE NEEDS • Explore the pos
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19 Berman KF, Schmidt PJ, Rubinow D
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64 Lerner A, Koss E, Debanne S, Row
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114 Smith R, Studd JW. A pilot stud
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162 Klein BE. Lens opacities in wom
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patients with strong personal convi
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Therefore, convincing evidence of t
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3.1.1 Risk Factors Many factors are
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278 lower dosages of estrogen will
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• Diabetes: Women with diabetes b
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Lipids and lipoproteins • LDL cho
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284 persists but is less steep in w
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5.2.3 Pharmacotherapy Breast Cancer
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• There is no clinical trial evid
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Sirtori CR, Pazzucconi F, Colombo L
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Hansson L, Zanchetti A, Carruthers
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Dementia and Mental Health Forette
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CRP C-reactive protein CT computed
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PTCA percutaneous transluminal coro
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U.S. DEPARTMENT OF HEALTH AND HUMAN
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