Undertreatment of menopausal symptoms and novel options for comprehensive management

Current Medical Research and Opinion

Volumn 25, Issue 11, 2009, Pages 2689-2698

  Lewis, Vivian ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Estrogens, conjugated; Hormone therapy; Menopause; Osteoporosis; Selective estrogen receptor modulators; Vasomotor symptoms

Indexed keywords

BAZEDOXIFENE; CONJUGATED ESTROGEN; CONJUGATED ESTROGEN PLUS MEDROXYPROGESTERONE ACETATE; DROSPIRENONE PLUS ESTRADIOL; ESTRADIOL; ESTRADIOL PLUS LEVONORGESTREL; ESTRADIOL PLUS NORETHISTERONE ACETATE; ESTRATEST; ESTROGEN; FLUOXETINE; GABAPENTIN; ISOFLAVONE; MEDROXYPROGESTERONE; MEDROXYPROGESTERONE ACETATE; MF 101; MIRTAZAPINE; NORETHISTERONE; NORGESTIMATE; ORG 50081; PD 299685; PIPERAZINE ESTRONE SULFATE; PLANT EXTRACT; RALOXIFENE; S MIRTAZAPINE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SEROTONIN 1 ANTAGONIST; TIBOLONE; TRIMEGESTONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VENLAFAXINE;

AMENORRHEA; BREAST CANCER; COST OF ILLNESS; DEEP VEIN THROMBOSIS; DRUG DOSE REGIMEN; DRUG DOSE SEQUENCE; DRUG EFFICACY; DRUG INTERMITTENT THERAPY; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; ENDOMETRIUM HYPERPLASIA; HORMONAL THERAPY; HOT FLUSH; HUMAN; INSOMNIA; LOW DRUG DOSE; MENOPAUSE; METRORRHAGIA; NIGHT SWEAT; OSTEOPOROSIS; PATIENT COMPLIANCE; POSTMENOPAUSE; POSTMENOPAUSE OSTEOPOROSIS; PRACTICE GUIDELINE; QUALITY OF LIFE; REVIEW; TREATMENT CONTRAINDICATION; TREATMENT DURATION; VAGINA ATROPHY; VAGINA BLEEDING; VASOMOTOR DISORDER; WOMEN'S HEALTH;

ATTITUDE TO HEALTH; BEHAVIORAL SYMPTOMS; COMPREHENSIVE HEALTH CARE; COST OF ILLNESS; ESTROGEN REPLACEMENT THERAPY; FEMALE; HUMANS; MENOPAUSE; OSTEOPOROSIS, POSTMENOPAUSAL; QUALITY OF HEALTH CARE; QUALITY OF LIFE; VAGINAL DISEASES; VASOMOTOR SYSTEM;

EID: 72549106915     PISSN: 03007995     EISSN: 14734877     Source Type: Journal    
DOI: 10.1185/03007990903240519     Document Type: Review

References (94)

1. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med 2005;142:1003-1013
2. Hill K. The demography of menopause. Maturitas 1996;23:113-127
3. Ford K, Sowers M, Crutchfield M, et al. A longitudinal study of the predictors of prevalence and severity of symptoms commonly associated with menopause. Menopause 2005;12:308-317 (Pubitemid 40664213)
4. Samsioe G. Urogenital aging - a hidden problem. Am J Obstet Gynecol 1998;178:S245-S249
5. Fugate Woods N, Sullivan Mitchell E. Symptoms during the perimenopause: prevalence, severity, trajectory, and significance in women's lives. Am J Med 2005;118:14S-24S
6. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006;13:340-367
7. Looker AC, Orwoll ES, Johnston Jr CC, et al. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 1997;12:1761-1768
8. Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 2004;291:47-53
9. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes 2005;3:47
10. Dennerstein L, Dudley EC, Hopper JL, et al. A prospective population-based study of menopausal symptoms. Obstet Gynecol 2000;96:351-358
11. Whiteman MK, Staropoli CA, Langenberg PW, et al. Smoking, body mass, and hot flashes in midlife women. Obstet Gynecol 2003;101:264-272 (Pubitemid 36170127)
12. The 2002 Gallup study of consumers' and physicians' changing HRT concerns. Qualitative Phase I & II. Princeton, NJ: Multi-Sponsor Surveys, Inc., 2002
13. Gold EB, Sternfeld B, Kelsey JL, et al. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol 2000;152:463-473 (Pubitemid 30696368)
14. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17:1726-1733 (Pubitemid 44607392)
15. Silverman SL, Minshall ME, Shen W, et al. The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study. Arthritis Rheum 2001;44:2611-2619 (Pubitemid 33049339)
16. Bobula JD. Vasomotor symptoms and quality of life (QoL) in postmenopausal women. Value Health 2003;6:707
17. Twiss JJ, Wegner J, Hunter M, et al. Perimenopausal symptoms, quality of life, and health behaviors in users and nonusers of hormone therapy. J Am Acad Nurse Pract 2007;19:602-613
18. Gold DT. The nonskeletal consequences of osteoporotic fractures. Psychologic and social outcomes. Rheum Dis Clin North Am 2001;27:255-262
19. Kjerulff KH, Frick KD, Rhoades JA, et al. The cost of being a woman: a national study of health care utilization and expenditures for female-specific conditions. Womens Health Issues 2007;17:13-21
20. Hoerger TJ, Downs KE, Lakshmanan MC, et al. Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks. J Womens Health Gend Based Med 1999;8:1077-1089
21. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-333
22. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712 (Pubitemid 38489892)
23. Grady D, Sawaya GF. Discontinuation of postmenopausal hormone therapy. Am J Med 2005;118:163-165
24. North American Menopause Society. Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause 2008;15:584-602
25. Stephenson J. FDA orders estrogen safety warnings: agency offers guidance for HRT use. JAMA 2003;289:537-538 (Pubitemid 37428620)
26. Grady D. Clinical practice. Management of menopausal symptoms. N Engl J Med 2006;355:2338-2347
27. Klaiber EL, Vogel W, Rako S. A critique of the Women's Health Initiative hormone therapy study. Fertil Steril 2005;84:1589-1601 (Pubitemid 41785650)
28. Hing E, Brett KM. Changes in U.S. prescribing patterns of menopausal hormone therapy, 2001-2003. Obstet Gynecol 2006;108:33-40
29. Rolnick SJ, Jackson J, Kopher R, et al. Provider management of menopause after the findings of the Women's Health Initiative. Menopause 2007;14:441-449
30. Ghali WA, Freund KM, Boss RD, et al. Menopausal hormone therapy: physician awareness of patient attitudes. Am J Med 1997;103:3-10
31. Schonberg MA, Wee CC. Menopausal symptom management and prevention counseling after the Women's Health Initiative among women seen in an internal medicine practice. J Womens Health (Larchmt) 2005;14:507-514
32. French LM, Smith MA, Holtrop JS, et al. Hormone therapy after the Women's Health Initiative: a qualitative study. BMC Fam Pract 2006;7:61
33. van de Weijer PH, Mattsson LA, Ylikorkala O. Benefits and risks of long-term low-dose oral continuous combined hormone therapy. Maturitas 2007;56:231-248 (Pubitemid 46241755)
34. Utian WH, Shoupe D, Bachmann G, et al. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril 2001;75:1065-1079 (Pubitemid 32522600)
35. Lindsay R, Gallagher JC, Kleerekoper M, et al. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 2002;287:2668-2676 (Pubitemid 34533545)
36. Archer DF, Dorin M, Lewis V, et al. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding. Fertil Steril 2001;75:1080-1087 (Pubitemid 32522601)
37. Pickar JH, Yeh IT, Wheeler JE, et al. Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate: two-year substudy results. Fertil Steril 2003;80:1234-1240
38. Gambacciani M, Spielmann D, Genazzani AR. Efficacy on climacteric symptoms of a continuous combined regimen of 1mg 17β-estradiol and trime-gestone versus two regimens combining 1 or 2 mg 17β-estradiol and norethisterone acetate. Gynecol Endocrinol 2005;21:65-73 (Pubitemid 41345498)
39. Koninckx PR, Spielmann D. A comparative 2-year study of the effects of sequential regimens of 1mg 17β-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women. Gynecol Endocrinol 2005;21:82-89 (Pubitemid 41345500)
40. Pornel B, Spielmann D. A study of the control of climacteric symptoms in postmenopausal women following sequential regimens of 1mg 17β-estradiol and trimegestone compared with a regimen containing 1mg estradiol valerate and norethisterone over a 2-year period. Gynecol Endocrinol 2005;21:74-81 (Pubitemid 41345499)
41. Archer DF. Drospirenone and estradiol: a new option for the postmenopausal woman. Climacteric 2007;10:3-10 (Pubitemid 46272640)
42. Whitehead M. Hormone replacement therapy with estradiol and drospirenone: an overview of the clinical data. J Br Menopause Soc 2006;12:4-7 (Pubitemid 43349423)
43. Greenwald MW, Gluck OS, Lang E, Rakov V. Oral hormone therapy with 17β-estradiol and 17β-estradiol in combination with norethindrone acetate in the prevention of bone loss in early postmenopausal women: dose-dependent effects. Menopause 2005;12:741-748 (Pubitemid 41669127)
44. Rowan JP, Simon JA, Speroff L, et al. Effects of low-dose norethindrone acetate plus ethinyl estradiol (0.5 mg/2.5 μg) in women with postmenopausal symptoms: updated analysis of three randomized, controlled trials. Clin Ther 2006;28:921-932 (Pubitemid 44081952)
45. Franke HR, Snaaijer FF, Houben PW, et al. Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment - a randomized, placebo-controlled, double-blind trial. Gynecol Endocrinol 2006;22:692-697
46. Adler G, Young D, Galant R, et al. A multicenter, open-label study to evaluate satisfaction and menopausal quality of life in women using transdermal estradiol/norethindrone acetate therapy for the management of menopausal signs and symptoms. Gynecol Obstet Invest 2005;59:212-219 (Pubitemid 40874860)
47. Tice JA, Grady D. Alternatives to estrogen for treatment of hot flashes: are they effective and safe? JAMA 2006;295:2076-2078
48. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society. Menopause 2004;11:11-33
49. North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of the North American Menopause Society. Menopause 2007;14:1-17
50. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause 2007;14:357-369
51. American College of Obstetricians and Gynecologists Women's Health Care Physicians. Executive summary. Hormone therapy. Obstet Gynecol 2004;104:1S-4S
52. Gelfand MM, Moreau M, Ayotte NJ, et al. Clinical assessment and quality of life of postmenopausal women treated with a new intermittent progestogen combination hormone replacement therapy: a placebo-controlled study. Menopause 2003;10:29-36 (Pubitemid 36706319)
53. Corson SL, Richart RM, Caubel P, Lim P. Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17β-estradiol and norgestimate on endometrial histology. Int J Fertil Womens Med 1999;44:279-285 (Pubitemid 30043394)
54. Rozenberg S, Caubel P, Lim PC. Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms. Int J Gynaecol Obstet 2001;72:235-243 (Pubitemid 32156925)
55. Sulak PJ, Caubel P, Lane R. Efficacy and safety of a constant-estrogen, pulsed-progestin regimen in hormone replacement therapy. Int J Fertil Womens Med 1999;44:286-296 (Pubitemid 30043395)
56. Arrenbrecht S, Caubel P, Garnero P, et al. The effect of continuous oestradiol with intermittent norgestimate on bone mineral density and bone turnover in post-menopausal women. Maturitas 2004;48:197-207 (Pubitemid 38781145)
57. Al-Baghdadi O, Ewies AA. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric 2009;12:91-105
58. Samsioe G, Boschitsch E, Concin H, et al. Endometrial safety, overall safety and tolerability of transdermal continuous combined hormone replacement therapy over 96 weeks: a randomized open-label study. Climacteric 2006;9:368-379 (Pubitemid 44454528)
59. Bachmann GA, Schaefers M, Uddin A, et al. Lowest effective transdermal 17β-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2007;110:771-779 (Pubitemid 47508739)
60. Shulman LP, Yankov V, Uhl K. Safety and efficacy of a continuous once-a-week 17β-estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials. Menopause 2002;9:195-207 (Pubitemid 34492328)
61. Al-Azzawi F, Buckler HM. Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms. Climacteric 2003;6:118-127 (Pubitemid 36714084)
62. Simon JA, Bouchard C, Waldbaum A, et al. Low dose of transdermal estradiol gel for treatment of symptomatic postmenopausal women: a randomized controlled trial. Obstet Gynecol 2007;109:588-596 (Pubitemid 46339398)
63. Delmas PD, Ensrud KE, Adachi JD, et al. Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 2002;87:3609-3617
64. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999;282:637-645 (Pubitemid 29384151)
65. Seeman E, Crans GG, Diez-Perez A, et al. Anti-vertebral fracture efficacy of raloxifene: a meta-analysis. Osteoporos Int 2006;17:313-316 (Pubitemid 43053597)
66. Delmas PD, Bjarnason NH, Mitlak BH, 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
67. Swanson SG, Drosman S, Helmond FA, et al. Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study. Menopause 2006;13:917-925 (Pubitemid 44760384)
68. Howes LG, Howes JB, Knight DC. Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis. Maturitas 2006;55:203-211 (Pubitemid 44397351)
69. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev 2006;CD001500
70. McDonnell DP. The molecular pharmacology of SERMs. Trends Endocrinol Metab 1999;10:301-311
71. Hall JM, McDonnell DP. The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 1999;140:5566-5578
72. Shelly W, Draper MW, Krishnan V, et al. Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv 2008;63:163-181 (Pubitemid 351612435)
73. Bushardt RL, Turner JL, Ragucci KR, Askins Jr DG. Non-estrogen treatments for osteoporosis: an evidence-based review. JAAPA 2006;19:25-30
74. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2727-2741 (Pubitemid 43920726)
75. Gold DT, Silverman SL. Do estrogen or selective estrogen receptor modulators improve quality of life for women with postmenopausal osteoporosis? Curr Osteoporos Rep 2007;5:3-7
76. Society of Obstetricians and Gynaecologists of Canada. SOGC clinical practice guidelines. The detection and management of vaginal atrophy. Number 145, May 2004. Int J Gynaecol Obstet 2005;88:222-228
77. Lindsay R, Gallagher JC, Kagan R, et al. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril 2009;92:1045-1052
78. Lobo RA, Pinkerton JV, Gass MLS, et al. Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertil Steril 2009;92:1025-1038
79. Pinkerton JV, Utian WH, Constantine GD, et al. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial [published online ahead of print June 10, 2009]. Menopause. doi:10.1097/gme. 0b013e3181a7df0d
80. Pickar JH, Yeh I-T, Bachmann G, Speroff L. Endometrial effects of a tissue selective estrogen complex containing bazedoxifene/conguated estrogens as a menopausal therapy. Fertil Steril 2009;92:1018-1024
81. Archer DF, Lewis V, Carr BR, et al. Bazedoxifene/conjugated estrogens (BZA/CE): incidence of uterine bleeding in postmenopausal women. Fertil Steril 2009;92:1039-1044
82. Cvoro A, Paruthiyil S, Jones JO, et al. Selective activation of estrogen receptor-beta transcriptional pathways by an herbal extract. Endocrinology 2007;148:538-547 (Pubitemid 46150775)
83. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071 (Pubitemid 44794007)
84. Speroff L, Gass M, Constantine G, et al. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol 2008;111:77-87
85. Kharode Y, Bodine PV, Miller CP, et al. The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. Endocrinology 2008;149:6084-6091
86. Komm BS. A new approach to menopausal therapy: the tissue selective estrogen complex. Reprod Sci 2008;15:984-992
87. Komm BS, Kharode YP, Bodine PV, et al. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146:3999-4008 (Pubitemid 41175771)
88. Komm BS, Lyttle CR. Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation. Ann N Y Acad Sci 2001;949:317-326
89. Miller PD, Chines AA, Christiansen C, et al. Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res 2008;23:525-535
90. Pinkerton JV, Archer DF, Utian WH, et al. Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis [published online ahead of print June 10, 2009]. Menopause. doi:10.1097/gme. 0b012e3181a816be
91. Silverman SL, Christiansen C, Genant HK, et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo- and active-controlled clinical trial. J Bone Miner Res 2008;23:1923-1934
92. HRT: what are women (and their doctors) to do? Lancet 2004;364:2069-2070 (Pubitemid 39626789)
93. Rolnick SJ, Kopher RA, DeFor TA, et al. Hormone use and patient concerns after the findings of the Women's Health Initiative. Menopause 2005;12:399-404 (Pubitemid 41098652)
94. Singh B, Liu XD, Der-Martirosian C, et al. A national probability survey of American Medical Association gynecologists and primary care physicians concerning menopause. Am J Obstet Gynecol 2005;193:693-700 (Pubitemid 41261464)