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available hormone formulation suits all women. Prolonged and/or heavy cyclical bleeding may be due to excess estrogen or insufficient progestin in the sequential formula- In observational tion or to endometrial pathology. Breakthrough bleeding is associated studies, ERT with a hyperplastic endometrium reduces the but may also occur with an atrophic endometrium. Continuous adminis- frequency of tration of progestins with estrogens urinary tract has been suggested to prevent the infections in the cyclical withdrawal bleeding associated with hormone regimens. postmenopausal A high incidence of irregular bleed- years. ing episodes (50 percent) has been observed during the first year. • Transvaginal ultrasonographic measurement of endometrial thickness provides a noninvasive clinical indicator of endometrial status. Endometrial thickness < 4 mm usually corresponds to histologically atrophic endometrium; thickness greater than 4 to 7 mm correlates with increased incidence of endometrial pathology in postmenopausal women. The exact level is uncertain in women receiving HRT whose endometrium is often thicker than in untreated postmenopausal women. Present-day ultrasound scanning cannot replace histopathologic assessment of the endometrium in women receiving HRT. Management of bleeding during HRT includes observation, surgery, and specific changes in the treatment regimen. 9.2 Lower Genital and Urinary Tract Atrophy • The epithelium of the inner layer of the vagina has high levels of ERs and undergoes progressive loss of cells during menopause due to estrogen depletion. Estrogen-dependent secretions decrease, leading to vaginal dryness and, in some women, vaginitis, vaginismus, and dispareunia. Local estrogen proved as effective as systemic in treatment for vaginal dryness [A]. • Loss of glycogen-producing cells, a consequence 16 of vaginal and urethral atrophy, causes decreased production of lactic acid and an environment that favors vaginal and urethral infection. It is important to identify and treat patients with recurrent infections to prevent significant morbidity, which includes risk for renal impairment. • In observational studies, ERT reduces the frequency of urinary tract infections in the postmenopausal years [D]. Its beneficial effects can partially be explained through its support of normal vaginal flora. 9.3 Pelvic Floor and Urinary Incontinence • All four functional layers of the urethra— epithelium, connective tissue, vascular tissue, and muscle—are affected by estrogen status. Estrogen deficiency causes atrophic changes of the urethral epithelium and of the submucosa. • Urinary incontinence (UI) is defined by the International Continence Society as involuntary loss of urine that is objectively demonstrable and is a social or hygienic problem. • The relationship between menopause and UI is unknown and not well studied. Limited data are available to support the hypothesis that menopause is a major risk factor for incontinence, especially for stress and urge incontinence. • Established UI can usually be divided as follows: stress incontinence, which occurs in the absence of detrusor activity; urge incontinence, when detrusor muscle contracts during the filling phase of the bladder; mixed incontinence, which is a combination of both stress and urge incontinence; and overflow incontinence, which is the result of bladder obstruction or injury. Other factors that can cause UI include decreased mobility, cognitive impairment, or medications. • Evaluation and treatment for incontinence is dependent on the type of incontinence and the person’s age, medical history, and desire for therapy.
9.3.1 Interventions • In many cases, urine leakage can be prevented or improved by improving pelvic muscle tone through different kinds of exercises. Pelvic floor exercises (including Kegel exercises), vaginal weight training, and pelvic floor electrical stimulation significantly reduce incontinence in RCTs [A]. • Behavioral therapies can help patients regain control of bladder function. Bladder training teaches people to resist the urge to void and gradually expand the intervals between voiding. Toilet assistance uses routine or scheduled toileting, habit training schedules, and prompted voiding to empty the bladder regularly to prevent leaking. • Pharmacological therapies for the treatment of UI vary accordingly to the kind of incontinence that needs to be treated. • Muscarinic receptor antagonists. Both tolterodine tatrate and oxybutinine significantly increased volume-voided/micturition and decreased micturition and incontinence episodes per 24 hours compared to placebo, but tolterodine only was significantly better than placebo in reducing micturition frequency [A]. • Hormone replacement therapy. Uncontrolled trials showed subjective improvement of incontinence upon estrogen treatment, while no objective improvement in measures of urine loss was found in RCTs [A]. HERS found HRT to be associated with worsening of stress UI [A]. By reducing potential afferent stimuli from the bladder, such as lower urinary tract infections, estrogen may benefit urge incontinence [C]. • Bulking injections. Periurethral injection of collagen in women with genuine stress incontinence and intrinsic sphincter deficiency has a low short-term cure rate and has not been shown to improve stress incontinence long-term [A]. • Surgical treatment. This intervention can be very effective in improving or curing stress incontinence. 10. MENOPAUSAL THERAPIES <strong>AND</strong> CANCER Experimental, clinical, and epidemiological data support an important role for reproductive hormones in the aetiology of some human cancers, including breast, endometrium, and ovary. Whereas for common adult cancers, such as lung and colon cancers, incidence rises continuously and progressively with age, the slope of increase slows around the time of menopause for most hormone-dependent cancers. Worldwide, breast cancer is by far the most frequent invasive cancer in women and the leading cause of cancer death in women, accounting for more than 300,000 deaths each year. Ovarian cancer adds another 100,000 deaths each year, and cancer of the corpus uteri adds 40,000. The issue of the effect of menopausal therapies on risk for cancer is a critical one. 10.1 Hormone Replacement Therapy Most of the potential favourable and adverse effects of HRT on cancer risks are restricted to current users. • Breast cancer. In observational studies, there is no appreciable association between less than 5 years of use of HRT and risk for breast cancer. Longer use is associated with a small but significant excess breast cancer risk for current users but not for former users. Combined HRT may be associated with higher breast cancer risk compared with unopposed estrogen. Worldwide, breast cancer is by far the most frequent invasive cancer in women and the leading cause of cancer death in women. 17
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 and 24: symptom measures, cultural factors,
Page 25 and 26: 5. PHYSIOLOGICAL ROLE OF ESTROGEN A
Page 27 and 28: The atherogenic risk profile of old
Page 29 and 30: • Hormone replacement therapy: Fi
Page 31: tion of the remaining ridge in area
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
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
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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
Page 110 and 111:
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
Page 206 and 207:
How should this information be inco
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emergence of proved treatment alter
Page 210 and 211:
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
Page 228 and 229:
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
Page 234 and 235:
21 Ferenczy A. Endometrial carcinom
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65 Wyman JF, Fantl JA, McClish DK,
Page 238 and 239:
222
Page 240 and 241:
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
Page 312 and 313:
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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