WOMEN 'S HEALTH AND MENOPAUSE : - National Heart, Lung ...

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• Physical activity. Evidence is conflicting as to whether increased physical activity affects menopausal symptoms. • Foods and beverages. Avoidance of hot beverages, foods containing nitrites or sulfites, spicy foods, and alcohol may help limit hot flushes. • Phytoestrogens. Although some evidence suggests that dietary supplementation with phytoestrogens yields improvements in hot flushes, the issue Estrogen therapy is remains unclear because of effective in reducing methodologic limitations of the studies. hot flushes. 8 • Gamma-linolenic acid. Gamma-linolenic acid provided in evening primrose oil, a popular alternative therapy, appears to offer no benefit over placebo in the treatment of vasomotor symptoms [B]. 3.2 Vulvovaginal Atrophic Symptoms Atrophic changes of the vulva, vagina, and lower urinary tract are common causes of complaints among menopausal women. Only vulvovaginal atrophic changes can be clearly related to menopause; findings as to whether disorders of urinary tract atrophy are menopause or age related are conflicting. (See also “Lower Genital and Urinary Tract Atrophy” in “Gynecologic and Urinary Aspects” below.) With estrogen loss, the vagina shortens and narrows, and its walls become thinner. Decreased production of lactic and acetic acids alters the normal low vaginal pH, to create a milieu that does not favor continued growth of the normal flora. A decrease in estrogen-supported lubrication causes vaginal dryness, which can lead to vaginitis, vaginismus, and dyspareunia. Cystocele and rectocele are also common problems in postmenopausal women. • Hormone replacement therapy. Estrogen therapy is effective in relieving vulvovaginal atrophic symptoms, and local estrogen preparations are as effective as systemic ones [A]. In observational studies, ERT reduces the frequency of urinary tract infections in the menopausal years [D]. 3.3 Mastalgia (Breast Soreness/Tenderness) In clinical trials, mastalgia has been related to estrogen and progestin concentrations [A]. Mastalgia that is related to the menstrual period often resolves with menopause. Compliance with HRT can be limited by the side effect of mastalgia. 4. SOCIOCULTURAL ISSUES • Attitudes toward and beliefs about menopause vary historically and among cultures [C]. • Cross-cultural comparisons demonstrate that reported symptoms can vary significantly among countries and among ethnic groups within countries in type (e.g., vasomotor, psychologic) and in the degree of distress caused [C]. • Difficulties in integrating findings from crosscultural studies stem from a number of limitations. Among these are differences among cultures in language used to describe symptoms, use of different methodologies in study design and in instruments used to measure symptoms, and differences in diet and other lifestyle factors that make it difficult to establish cultural versus biologic causes of symptom expression. • Abetter appreciation of cross-cultural differences in the experience of menopause may derive from an emerging interdisciplinary model in which symptoms are seen as a result of increased vulnerability due to hormonal changes in interaction with psychologic and sociocultural factors.
5. PHYSIOLOGICAL ROLE OF ESTROGEN <strong>AND</strong> ESTROGEN RECEPTORS <strong>AND</strong> PHARMACOLOGIC MODULATION OF ESTROGEN RECEPTOR ACTIVITY • The two known estrogen receptor (ER) subtypes, ERα and ERβ, mediate many biologic effects of estrogens and antiestrogens. • Different ligands induce different ER conformations. • Different mechanisms of target gene regulation affect the agonist/antagonist profile of a ligand. Selective ER modulators (SERMs) have a tissueand gene-specific mixed agonist/antagonist effect. • Of interest are the SERMs (third-generation HRT), nonsteroidal agents that behave as agonists in target tissues such as bone and liver and as antagonists or partial agonists in reproductive tissues [A/B]. • Both subtypes are also important for normal ovarian follicular development and female fertility. • Available data suggest that ERα plays an important role in bone maturation and homeostasis in both women and men, and that ERβ has a specific role in bone physiology in women. • ERα and ERβ are expressed in vascular endothelial cells, vascular smooth muscle cells, and myocardial cells. Beneficial effects of estrogens on cardiovascular function and reactivity stem from direct effects on cells in the vascular system and also from effects on liver and on circulating monocytes/macrophages. • In the central nervous system (CNS), estrogen is linked to a variety of functions, including learning, memory, awareness, fine motor skills, temperature regulation, mood, reproductive functions, and depression. The predominance of expression and localization of ERβ in rat neocortex, hippocampus, and nuclei of the basal forebrain suggests an important role for ERβ in learning and memory. • Estrogen and inhibins produced by the ovaries are important feedback regulators of the hypothalamic-pituitary axis and serum concentrations of luteinizing hormone (LH) and FSH. ERα seems to be more involved than ERβ in the LH, FSH feedback loop. • Increased knowledge of the structure of ERs and of the mechanisms of the receptors’ synthesis and their interaction with key elements of the transcription apparatus is facilitating the synthesis of new pharmacologically active molecules. • ERα- and ERβ-selective SERMs in development might provide improved therapy. Since both ER subtypes are expressed in human breast cancer, measurements of both ERα and ERβ may help in the selection of appropriate breast cancer therapy. 5.1 Hormone Replacement Therapy and Related Therapies The regimens most commonly used to treat climacteric symp- The two known toms and to intervene against ER subtypes, ERα menopausal and postmenopausal health risks are and ERβ, mediate 17β-estradiol, esterified estro- many biologic gens, and conjugated equine effects of estrogens estrogens (CEEs) in combination with a progestin, for and antiestrogens. example, medroxyprogesterone acetate (MPA). The awareness of undesired effects and serious health risks (breast cancer, endometrial cancer, and venous thromboembolism) with existing HRT call for alternatives with improved safety profiles. Alternative regimens for women who do not wish to take estrogen exist. Non-ER subtype-selective SERMs display tissue-selective estrogen agonism. They do not increase the risk of breast and endometrial cancer but aggravate hot flushes and increase the risk of venous thromboembolism. The existence of two ER subtypes provides the oppor- 9
Page 1: National Heart, Lung, and Blood Ins
Page 4 and 5: CHAIRS AND EDITORS Chair and Editor
Page 6 and 7: Anne McTiernan, M.D., Ph.D. Associa
Page 8 and 9: Lenore Manderson, Ph.D. Director an
Page 10 and 11: Michael Mendelsohn, M.D. Director,
Page 13 and 14: TABLE OF CONTENTS Preface XIII 1 Ex
Page 15 and 16: PREFACE Women’s health and menopa
Page 17 and 18: CHAPTER 1: EXECUTIVE SUMMARY Nanett
Page 19 and 20: TABLE 1-1 Evidence Categories Evide
Page 21 and 22: TABLE 1-2 (continued) Possible Bene
Page 23: symptom measures, cultural factors,
Page 27 and 28: The atherogenic risk profile of old
Page 29 and 30: • Hormone replacement therapy: Fi
Page 31 and 32: tion of the remaining ridge in area
Page 33 and 34: 9.3.1 Interventions • In many cas
Page 35 and 36: Parkinson’s disease, no overall p
Page 37 and 38: TABLE 1-3 (continued) Sexuality •
Page 39 and 40: CHAPTER 2: THE MENOPAUSE AND AGING
Page 41 and 42: oped and are less prepared to addre
Page 43 and 44: FIGURE 2-4 Diabetes Mellitus. Estim
Page 45 and 46: Sarcopenia, defined as reduced musc
Page 47 and 48: Perimenopause WHO The term “perim
Page 49 and 50: decrease about 2 years before the F
Page 51 and 52: 4.3 Menstrually Defined Menopausal
Page 53 and 54: to be under stress and to hold part
Page 55 and 56: 21 Brincat MP. Hormone replacement
Page 57 and 58: 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
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48 Avis NE, Crawford SL, McKinlay S
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92 Albertazzi P, Pansini F, Bonacco
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Hällström wrote that the psycholo
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countries. Perhaps, as the authors
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Beyene used a systematic ethnograph
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ange of variables, such as genetic
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REFERENCES 1 Gannon L, Ekstrom B. A
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47 George T. Women in a south India
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9. Estrogen and inhibins produced b
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HRT) display tissue-selective estro
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a partial agonist. In contrast, wit
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3. UROGENITAL TRACT ERα and ERβ a
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4. BONE: DEVELOPMENT AND HOMEOSTASI
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in response to estrogen. 106,105 In
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lation of sleep, motor behavior, an
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7. HORMONE REPLACEMENT THERAPY: TRA
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REFERENCES 1 Jensen EV, Jacobsen HI
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40 Power RF, Mani SK, Codina J, Con
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83 Oursler MJ, Pederson L, Fitzpatr
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125 Gabrielsson BG, Carmignac DF, F
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169 Renier MA, Vereecken A, Buytaer
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FIGURE 6-1 Structural features of E
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ound, the conformation of the recep
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with extremely potent estrogenic ac
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Its potency as an antiestrogen was
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The observation that the degree of
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findings were remarkable because a
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Recently, the use of phage display
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20 Crawley G. Non steroidal estroge
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65 Qu Q, Zheng H, Dahllund J, et al
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in their survey of postmenopausal w
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where over half the world’s popul
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The Danish study of Koster and Gard
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Many studies of sexual interest in
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7. ASSESSING SEXUAL ACTIVITY Clinic
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None of these studies evaluated the
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estrogen-androgen group during the
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REFERENCES 1 Sarrel PM, Whitehead M
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52 Utian WH. The true clinical feat
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140
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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
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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
Page 316:
U.S. DEPARTMENT OF HEALTH AND HUMAN
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