Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point of care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

For more information, click below.


Subscribers log in here


Postmenopausal hormone therapy: Benefits and risks

INTRODUCTION

Normal women have menopause at a mean age of 51 years, with 95 percent becoming menopausal between the ages of 45 to 55 years. Estrogen is the most effective treatment available for relief of menopausal symptoms, most importantly, hot flashes. Postmenopausal hormone therapy (estrogen alone or combined with a progestin) is currently indicated for management of menopausal symptoms.

An overview of the risks and benefits of postmenopausal hormone therapy will be provided here. The management of women with hot flashes and other menopausal symptoms is reviewed in greater detail separately. (See "Menopausal hot flashes" and "Treatment of menopausal symptoms with hormone therapy", section on 'Patient selection'.)

OVERVIEW

Postmenopausal hormone therapy continues to play an important role in the management of hot flashes. It is highly effective for the management of hot flashes, vaginal atrophy and, in some cases, the mood lability that many women experience during the menopausal transition [1]. Details on management of vasomotor symptoms are reviewed in detail separately. The use of vaginal estrogen for vaginal atrophy is also reviewed separately. (See "Treatment of menopausal symptoms with hormone therapy" and "Menopausal hot flashes" and "Treatment of vaginal atrophy".)

In the past, hormone therapy was also often prescribed for prevention of coronary heart disease (CHD) and osteoporosis, based upon epidemiologic data demonstrating a protective effect of estrogen on the heart and bone. However, data from the Women's Health Initiative (WHI), a set of two hormone therapy trials (unopposed estrogen and continuous, combined estrogen-progestin therapy versus placebo), in healthy postmenopausal women (mean age 63 years) showed a number of adverse outcomes, including an excess risk of CHD, stroke, venous thromboembolism, and breast cancer [2,3].

Similar results were noted in a meta-analysis of 23 trials [4], and an updated 2012 United States Preventive Services Task Force (USPSTF) meta-analysis of nine trials [5]. Both included the WHI, and the mean age of subjects was >60 years. In the USPSTF analysis, results were largely based upon the WHI. Based upon their current meta-analysis, the USPSTF continues to recommend against the use of both combined estrogen and progestin and unopposed estrogen (for women post-hysterectomy) for the prevention of chronic conditions [5,6]. However, they note that this recommendation does not apply to women considering using hormone therapy for relief of menopausal symptoms [6,7].

                                          

Subscribers log in here

To continue reading this article you must have access through your hospital or your group practice, log in to your personal subscription, or purchase a personal subscription. For more information, click below.
Literature review current through: Apr 2013. | This topic last updated: Apr 11, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2013 UpToDate, Inc.
References
Top
  1. Taylor HS, Manson JE. Update in hormone therapy use in menopause. J Clin Endocrinol Metab 2011; 96:255.
  2. 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.
  3. 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.
  4. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2012; 7:CD004143.
  5. Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. Ann Intern Med 2012; 157:104.
  6. Moyer VA, U.S. Preventive Services Task Force. Menopausal hormone therapy for the primary prevention of chronic conditions: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2013; 158:47.
  7. Rossouw JE, Manson JE, Kaunitz AM, Anderson GL. Lessons learned from the Women's Health Initiative trials of menopausal hormone therapy. Obstet Gynecol 2013; 121:172.
  8. Santen RJ, Allred DC, Ardoin SP, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010; 95:s1.
  9. Zhang SM, Manson JE, Rexrode KM, et al. Use of oral conjugated estrogen alone and risk of breast cancer. Am J Epidemiol 2007; 165:524.
  10. Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med 2003; 348:645.
  11. Col NF, Pauker SG. The discrepancy between observational studies and randomized trials of menopausal hormone therapy: did expectations shape experience? Ann Intern Med 2003; 139:923.
  12. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297:1465.
  13. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349:523.
  14. Shufelt CL, Johnson BD, Berga SL, et al. Timing of hormone therapy, type of menopause, and coronary disease in women: data from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation. Menopause 2011; 18:943.
  15. Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med 2007; 356:2591.
  16. Salpeter SR, Walsh JM, Greyber E, Salpeter EE. Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med 2006; 21:363.
  17. Kronos Early Estrogen Prevention Study http://www.keepstudy.org/news/index.cfm (Accessed on February 28, 2013).
  18. Kronos Longevity Research Institute. Press Release - Hormone therapy has many favorable effects in newly menopausal women: Initial findings of the Kronos Early Estrogen Prevention Study (KEEPS), October 2012 http://www.menopause.org/docs/agm/general-release.pdf?sfvrsn=0 (Accessed on February 28, 2013).
  19. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012; 345:e6409.
  20. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Trial does not change the conclusions of Cochrane review of long term hormone therapy for perimenopausal and postmenopausal women. BMJ 2012; 345:e8141; author reply e8164.
  21. Rossouw JE, Manson JE, Kaunitz AM, Stefanick ML. Study had insufficient power to investigate safety. BMJ 2012; 345:e8146; author reply e8164.
  22. Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 2003; 289:2673.
  23. Cushman M, Kuller LH, Prentice R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004; 292:1573.
  24. Hulley S, Furberg C, Barrett-Connor E, et al. Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 2002; 288:58.
  25. Salpeter SR, Cheng J, Thabane L, et al. Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal women. Am J Med 2009; 122:1016.
  26. Martin KA, Manson JE. Approach to the patient with menopausal symptoms. J Clin Endocrinol Metab 2008; 93:4567.
  27. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 2003; 289:3243.
  28. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997; 350:1047.
  29. Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 2003; 290:1739.
  30. Garg PP, Kerlikowske K, Subak L, Grady D. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Obstet Gynecol 1998; 92:472.
  31. Zhou B, Sun Q, Cong R, et al. Hormone replacement therapy and ovarian cancer risk: a meta-analysis. Gynecol Oncol 2008; 108:641.
  32. Kotsopoulos J, Lubinski J, Neuhausen SL, et al. Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol 2006; 100:83.
  33. Beral V, Bull D, Reeves G, Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005; 365:1543.
  34. Woodruff JD, Pickar JH. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol 1994; 170:1213.
  35. Schiff I, Sela HK, Cramer D, et al. Endometrial hyperplasia in women on cyclic or continuous estrogen regimens. Fertil Steril 1982; 37:79.
  36. Henderson BE. The cancer question: an overview of recent epidemiologic and retrospective data. Am J Obstet Gynecol 1989; 161:1859.
  37. Persson I, Adami HO, Bergkvist L, et al. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. BMJ 1989; 298:147.
  38. Weiderpass E, Adami HO, Baron JA, et al. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 1999; 91:1131.
  39. Strom BL, Schinnar R, Weber AL, et al. Case-control study of postmenopausal hormone replacement therapy and endometrial cancer. Am J Epidemiol 2006; 164:775.
  40. Shapiro S, Kelly JP, Rosenberg L, et al. Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 1985; 313:969.
  41. Chu J, Schweid AI, Weiss NS. Survival among women with endometrial cancer: a comparison of estrogen users and nonusers. Am J Obstet Gynecol 1982; 143:569.
  42. Genant HK, Lucas J, Weiss S, et al. Low-dose esterified estrogen therapy: effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Estratab/Osteoporosis Study Group. Arch Intern Med 1997; 157:2609.
  43. Johnson SR, Ettinger B, Macer JL, et al. Uterine and vaginal effects of unopposed ultralow-dose transdermal estradiol. Obstet Gynecol 2005; 105:779.
  44. Beresford SA, Weiss NS, Voigt LF, McKnight B. Risk of endometrial cancer in relation to use of oestrogen combined with cyclic progestagen therapy in postmenopausal women. Lancet 1997; 349:458.
  45. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1996; 275:370.
  46. Lacey JV Jr, Leitzmann MF, Chang SC, et al. Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort. Cancer 2007; 109:1303.
  47. Pike MC, Peters RK, Cozen W, et al. Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst 1997; 89:1110.
  48. Cerin A, Heldaas K, Moeller B. Adverse endometrial effects of long-cycle estrogen and progestogen replacement therapy. The Scandinavian LongCycle Study Group. N Engl J Med 1996; 334:668.
  49. Whitehead MI, Fraser D. The effects of estrogens and progestogens on the endometrium. Modern approach to treatment. Obstet Gynecol Clin North Am 1987; 14:299.
  50. Whitehead MI, Hillard TC, Crook D. The role and use of progestogens. Obstet Gynecol 1990; 75:59S.
  51. Jaakkola S, Lyytinen H, Pukkala E, Ylikorkala O. Endometrial cancer in postmenopausal women using estradiol-progestin therapy. Obstet Gynecol 2009; 114:1197.
  52. Weinstein L, Bewtra C, Gallagher JC. Evaluation of a continuous combined low-dose regimen of estrogen-progestin for treatment of the menopausal patient. Am J Obstet Gynecol 1990; 162:1534.
  53. Archer DF, Pickar JH, Bottiglioni F. Bleeding patterns in postmenopausal women taking continuous combined or sequential regimens of conjugated estrogens with medroxyprogesterone acetate. Menopause Study Group. Obstet Gynecol 1994; 83:686.
  54. Creasman WT, Henderson D, Hinshaw W, Clarke-Pearson DL. Estrogen replacement therapy in the patient treated for endometrial cancer. Obstet Gynecol 1986; 67:326.
  55. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 1995; 273:199.
  56. Ettinger B, Selby J, Citron JT, et al. Cyclic hormone replacement therapy using quarterly progestin. Obstet Gynecol 1994; 83:693.
  57. Hirvonen E, Salmi T, Puolakka J, et al. Can progestin be limited to every third month only in postmenopausal women taking estrogen? Maturitas 1995; 21:39.
  58. 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.
  59. Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 2004; 350:991.
  60. Cirillo DJ, Wallace RB, Rodabough RJ, et al. Effect of estrogen therapy on gallbladder disease. JAMA 2005; 293:330.
  61. Simon JA, Hunninghake DB, Agarwal SK, et al. Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2001; 135:493.
  62. Cauley JA, Robbins J, Chen Z, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 2003; 290:1729.
  63. Kanaya AM, Herrington D, Vittinghoff E, et al. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2003; 138:1.
  64. Margolis KL, Bonds DE, Rodabough RJ, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia 2004; 47:1175.
  65. Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993; 329:753.
  66. Cardozo L, Lose G, McClish D, et al. A systematic review of estrogens for recurrent urinary tract infections: third report of the hormones and urogenital therapy (HUT) committee. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12:15.
  67. Brown JS, Vittinghoff E, Kanaya AM, et al. Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Obstet Gynecol 2001; 98:1045.
  68. Stamm WE. Estrogens and urinary-tract infection. J Infect Dis 2007; 195:623.
  69. MacLennan A, Lester S, Moore V. Oral estrogen replacement therapy versus placebo for hot flushes: a systematic review. Climacteric 2001; 4:58.
  70. Col NF, Weber G, Stiggelbout A, et al. Short-term menopausal hormone therapy for symptom relief: an updated decision model. Arch Intern Med 2004; 164:1634.
  71. Hlatky MA, Boothroyd D, Vittinghoff E, et al. Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA 2002; 287:591.
  72. Rexrode KM, Manson JE. Postmenopausal hormone therapy and quality of life: no cause for celebration. JAMA 2002; 287:641.
  73. Greenspan SL, Resnick NM, Parker RA. The effect of hormone replacement on physical performance in community-dwelling elderly women. Am J Med 2005; 118:1232.
  74. Hays J, Ockene JK, Brunner RL, et al. Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 2003; 348:1839.
  75. Brunner RL, Gass M, Aragaki A, et al. Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial. Arch Intern Med 2005; 165:1976.
  76. Ekblad S, Bergendahl A, Enler P, et al. Disturbances in postural balance are common in postmenopausal women with vasomotor symptoms. Climacteric 2000; 3:192.
  77. Crilly RG, Delaquerrière Richardson L, Roth JH, et al. Postural stability and Colles' fracture. Age Ageing 1987; 16:133.
  78. Hammar ML, Lindgren R, Berg GE, et al. Effects of hormonal replacement therapy on the postural balance among postmenopausal women. Obstet Gynecol 1996; 88:955.
  79. Seeley DG, Cauley JA, Grady D, et al. Is postmenopausal estrogen therapy associated with neuromuscular function or falling in elderly women? Study of Osteoporotic Fractures Research Group. Arch Intern Med 1995; 155:293.
  80. Armstrong AL, Oborne J, Coupland CA, et al. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Clin Sci (Lond) 1996; 91:685.
  81. Brincat M, Versi E, Moniz CF, et al. Skin collagen changes in postmenopausal women receiving different regimens of estrogen therapy. Obstet Gynecol 1987; 70:123.
  82. Holland EF, Studd JW, Mansell JP, et al. Changes in collagen composition and cross-links in bone and skin of osteoporotic postmenopausal women treated with percutaneous estradiol implants. Obstet Gynecol 1994; 83:180.
  83. Maheux R, Naud F, Rioux M, et al. A randomized, double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thickness. Am J Obstet Gynecol 1994; 170:642.
  84. Ashcroft GS, Dodsworth J, van Boxtel E, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-beta1 levels. Nat Med 1997; 3:1209.
  85. Wolff EF, Narayan D, Taylor HS. Long-term effects of hormone therapy on skin rigidity and wrinkles. Fertil Steril 2005; 84:285.
  86. Sator PG, Sator MO, Schmidt JB, et al. A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women. Climacteric 2007; 10:320.
  87. Phillips TJ, Symons J, Menon S, HT Study Group. Does hormone therapy improve age-related skin changes in postmenopausal women? A randomized, double-blind, double-dummy, placebo-controlled multicenter study assessing the effects of norethindrone acetate and ethinyl estradiol in the improvement of mild to moderate age-related skin changes in postmenopausal women. J Am Acad Dermatol 2008; 59:397.
  88. Koomen ER, Joosse A, Herings RM, et al. Estrogens, oral contraceptives and hormonal replacement therapy increase the incidence of cutaneous melanoma: a population-based case-control study. Ann Oncol 2009; 20:358.
  89. Holly EA, Cress RD, Ahn DK. Cutaneous melanoma in women: ovulatory life, menopause, and use of exogenous estrogens. Cancer Epidemiol Biomarkers Prev 1994; 3:661.
  90. Tang JY, Spaunhurst KM, Chlebowski RT, et al. Menopausal hormone therapy and risks of melanoma and nonmelanoma skin cancers: women's health initiative randomized trials. J Natl Cancer Inst 2011; 103:1469.
  91. Nevitt MC, Cummings SR, Lane NE, et al. Association of estrogen replacement therapy with the risk of osteoarthritis of the hip in elderly white women. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1996; 156:2073.
  92. Zhang Y, McAlindon TE, Hannan MT, et al. Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: the Framingham Study. Arthritis Rheum 1998; 41:1867.
  93. Cirillo DJ, Wallace RB, Wu L, Yood RA. Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative. Arthritis Rheum 2006; 54:3194.
  94. Paganini-Hill A. The benefits of estrogen replacement therapy on oral health. The Leisure World cohort. Arch Intern Med 1995; 155:2325.
  95. Krall EA, Dawson-Hughes B, Hannan MT, et al. Postmenopausal estrogen replacement and tooth retention. Am J Med 1997; 102:536.
  96. Worzala K, Hiller R, Sperduto RD, et al. Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies. Arch Intern Med 2001; 161:1448.
  97. Freeman EE, Munoz B, Schein OD, West SK. Hormone replacement therapy and lens opacities: the Salisbury Eye Evaluation project. Arch Ophthalmol 2001; 119:1687.
  98. Waetjen LE, Brown JS, Vittinghoff E, et al. The effect of ultralow-dose transdermal estradiol on urinary incontinence in postmenopausal women. Obstet Gynecol 2005; 106:946.
  99. Troisi RJ, Speizer FE, Willett WC, et al. Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma. A prospective cohort study. Am J Respir Crit Care Med 1995; 152:1183.
  100. Lieberman D, Kopernik G, Porath A, et al. Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women. Maturitas 1995; 21:153.
  101. Hepburn MJ, Dooley DP, Morris MJ. The effects of estrogen replacement therapy on airway function in postmenopausal, asthmatic women. Arch Intern Med 2001; 161:2717.
  102. Meier CR, Sturkenboom MC, Cohen AS, Jick H. Postmenopausal estrogen replacement therapy and the risk of developing systemic lupus erythematosus or discoid lupus. J Rheumatol 1998; 25:1515.
  103. Sánchez-Guerrero J, Liang MH, Karlson EW, et al. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med 1995; 122:430.
  104. Akkad AA, Habiba MA, Ismail N, et al. Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities. Obstet Gynecol 1995; 86:330.
  105. Sener AB, Seçkin NC, Ozmen S, et al. The effects of hormone replacement therapy on uterine fibroids in postmenopausal women. Fertil Steril 1996; 65:354.
  106. Polatti F, Viazzo F, Colleoni R, Nappi RE. Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT. Maturitas 2000; 37:27.
  107. Palomba S, Sena T, Noia R, et al. Transdermal hormone replacement therapy in postmenopausal women with uterine leiomyomas. Obstet Gynecol 2001; 98:1053.
  108. Ang WC, Farrell E, Vollenhoven B. Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: a literature review. Climacteric 2001; 4:284.
  109. Yang CH, Lee JN, Hsu SC, et al. Effect of hormone replacement therapy on uterine fibroids in postmenopausal women--a 3-year study. Maturitas 2002; 43:35.
  110. Harden CL, Pulver MC, Ravdin L, Jacobs AR. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia 1999; 40:1402.
  111. Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA 2001; 286:2114.
  112. Nordin BE, Need AG, Morris HA, et al. Evidence for a renal calcium leak in postmenopausal women. J Clin Endocrinol Metab 1991; 72:401.
  113. Mattix Kramer HJ, Grodstein F, Stampfer MJ, Curhan GC. Menopause and postmenopausal hormone use and risk of incident kidney stones. J Am Soc Nephrol 2003; 14:1272.
  114. Maalouf NM, Sato AH, Welch BJ, et al. Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women's Health Initiative hormone therapy trials. Arch Intern Med 2010; 170:1678.
  115. Norman RJ, Flight IH, Rees MC. Oestrogen and progestogen hormone replacement therapy for peri-menopausal and post-menopausal women: weight and body fat distribution. Cochrane Database Syst Rev 2000; :CD001018.
  116. North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause 2012; 19:257.
  117. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the american heart association. Circulation 2011; 123:1243.
  118. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. ACOG Committee Opinion No. 420, November 2008: hormone therapy and heart disease. Obstet Gynecol 2008; 112:1189.