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RECOMMENDATIONS

Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health

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Pages 316-337 | Published online: 15 May 2013
 

Conflict of interest The authors report no associations or financial relationships with any pharmaceutical company, other than consultative agreements, honoraria for lecturing at scientific meetings, and research support. Details of all disclosures have been updated and are on file in the IMS Secretariat.

Source of funding The IMS Workshop in November 2012 was supported by unrestricted grants from Abbott GmbH, Bayer Pharma AG, Besins Healthcare, Novo Nordisk, Pfizer Inc., Shionogi Inc. and Teva.

2011 Updated IMS Recommendations Authors: D. W. Sturdee and A. Pines on behalf of the International Menopause Society Writing Group. Writing Group: D. F. Archer, R. J. Baber, D. Barlow, M. H. Birkhäuser, M. Brincat, L. Cardozo, T. J. de Villiers, M. Gambacciani, A. A. Gompel, V. W. Henderson, C. Kluft, R. A. Lobo, A. H. MacLennan, J. Marsden, R. E. Nappi, N. Panay, J. H. Pickar, D. Robinson, J. Simon, R. L. Sitruk-Ware and J. C. Stevenson.

Suggested Reading

General

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  • Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progesterone in healthy post-menopausal women. JAMA 2002;288:321–33
  • Anderson GL, Judd HL, Kaunitz AM, et al. for the Women's Health Initiative Investigators. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures. JAMA 2003;290:1739–48
  • Million Women Study Collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet 2003; 362:419–27
  • Asikainen TM, Kukkonen-Harjula K, Miilunpalo S. Exercise for health for early postmenopausal women. A systematic review of randomised controlled trials. Sports Med 2004;34:753–78
  • Harman SM, Brinton EA, Cedars M, Lobo R, et al. The Kronos Early Estrogen Prevention Study. An ongoing trial of the effects of early initiation of HRT on coronary artery disease. Climacteric 2005;8:3–12
  • Center for Media and Public Affairs; commissioned by the Hormone Foundation. Analysis of media coverage of hormone therapy for menopause management: 2002 through 2007. http://www.hormone.org/Menopause/upload/media-analysis-081309.pdf
  • Dubnov-Raz G, Pines A, Berry EM. Diet and lifestyle in managing postmenopausal obesity. Climacteric 2007;10(Suppl 2):38–41
  • Haskell WI, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation 2007;116:1081–93
  • Vickers MR, MacLennan AH, Lawton B, et al. Main morbidities recorded in the Women's International Study of long Duration Oestrogen after Menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ 2007; doi:10.1136/bmj.39266.425069.AD http://www.bmj.com/cgi/content/full/bmj.39266.425069.AD . Abridged print version BMJ 2007;335:239–44
  • Assessment and Management of Cardiovascular Risks in Women; a Short Guide for Menopause Physicians. Worthing, UK: Cambridge Medical Publications, 2008. Available for free download on the IMS website (www.imsociety.org)
  • Kenfield SA, Stampfer MJ, Rosner BA, Colditz GA. Smoking and smoking cessation in relation to mortality in women. JAMA 2008;299:2037–44
  • Moayyeri A. The association between physical activity and osteoporotic fractures: a review of the evidence and implications for future research. Ann Epidemiol 2008;18:827–35
  • Welton AJ, Vickers MR, Kim J, et al. Health related quality of life after combined hormone replacement therapy: randomised controlled trial. BMJ 2008;337: a1190.doi:10.1136/bmj.a1190
  • Aging, menopause, cardiovascular disease and HRT. Proceedings of the 8th IMS workshop. Climacteric 2009;12(Suppl 1)
  • Eliassen AH, Hankinson SE, Rosner B, et al. Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med 2010;170:1758–64
  • Friedenreich CM, Neilson HK, Lynch BM. State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer 2010;46:2593–604
  • Baer HJ, Glynn RJ, Hu FB, et al. Risk factors for mortality in the Nurses’ Health Study: a competing risks analysis. Am J Epidemiol 2011;173:319–29
  • Burger HG, MacLennan AH, Huang KE, Castelo-Branco C. Evidence-based assessment of the impact of the WHI on women’s health. Climacteric 2012;15:281–7
  • Langer RD, Manson JE, Allison MA. Have we come full circle – or moved forward? The Women’s Health Initiative 10 years on. Climacteric 2012;15:206–12
  • Pines A, Sturdee DW, Maclennan AH. Quality of life and the role of menopausal hormone therapy. Climacteric 2012;15:213–16
  • Purbrick B, Stranks K, Sum C, MacLennan AH. Future long-term trials of postmenopausal hormone replacement therapy – what is possible and what is the optimal protocol and regimen?Climacteric 2012;15:288–93
  • de Villiers TJ, Gass ML, Haines CJ, et al. Global Consensus Statement on Menopausal Hormone Therapy. Climacteric 2013;16:203–4
  • Panay N, Fenton A. A global consensus statement on menopause hormone therapy – aims, aspirations and action points. Climacteric 2013;16:201–2

Hormones and breast cancer

  • Million Women Study Collaborators. Breast cancer and HRT in the Million Women Study. Lancet 2003;362:419–27
  • Chen WY, Manson JE, Hankinson SE, et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 2006;166:1027–32
  • Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006;295: 1647–57
  • Fournier A, Fabre A, Mesrine S, et al. Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer. Int J Cancer 2008;26:1260–8
  • Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F. Estrogen-progestagen menopausal hormone therapy and breast cancer: does delay from menopause onset to treatment initiation influence risks?J Clin Oncol 2009;27:5138–3
  • Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obstet Gynecol 2009;113:65–73
  • Chlebowski RT, Anderson GL, Gass M, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 2010;304:1684–92
  • Gompel A, Plu-Bureau G. Is the decrease in breast cancer incidence related to a decrease in postmenopausal hormone therapy?Ann NY Acad Sci 2010;1205:268–76
  • Kerlikowske K, Cook AJ, Buist DS, et al. Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol 2010;28:3830–7
  • Bakken K, Fournier A, Lund E, et al. Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2011;128:144–56
  • Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol 2012;13:476–86
  • Crandall CJ, Aragaki AK, Cauley JA, et al. Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone Women’s Health Initiative clinical trials. Breast Cancer Res Treat 2012;132:275–85
  • Gompel A, Santen RJ. Hormone therapy and breast cancer risk 10 years after the WHI. Climacteric 2012;15:241–9
  • Nichols HB, Trentham-Dietz A, Newcomb PA, et al. Postoophorectomy estrogen use and breast cancer risk. Obstet Gynecol 2012;120:27–36
  • Ritte R, Lukanova A, Berrino F, et al. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res 2012;14:R76
  • Shapiro S, Farmer RD, Stevenson JC, Burger H, Mueck AO. Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. 4: The Million Women Study. J Fam Plann Reprod Health Care 2012;38:102–9

Ovarian, lung and other cancers

  • Grodstein F, Newcomb P, Stampfer M. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta- analysis. Am J Med 1999;106:574–82
  • Ritenbaugh C, Stanford J, Wu L, et al. Conjugated equine estrogens and colorectal cancer incidence and survival: the Women's Health Initiative randomized clinical trial. Cancer Epidemiol Biomarkers Prev 2008;17:2609–18
  • Marsden J, Sturdee D. Cancer issues. Best Pract Res Clin Obstet Gynaecol 2009;23:87–107
  • Morch L, Lokkegaard E, Andreasen A, et al. Hormone therapy and ovarian cancer. JAMA 2009;302:298–305
  • Chlebowski R, Anderson G, Manson J, et al. Lung cancer among postmenopausal women treated with estrogen alone in the Women's Health Initiative randomized trial. J Natl Cancer Inst 2010; 102:1413–21
  • Delellis Henderson K, Duan L, Sullivan-Halley J, et al. Menopausal hormone therapy use and risk of invasive colon cancer: the California Teachers Study. Am J Epidemiol 2010;171:415–25
  • Freedman ND, Lacey JV Jr, Hollenbeck AR, et al. The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH-AARP cohort. Cancer 2010;116:1572–81
  • Barnes EL, Long MD.Colorectal cancer in women: hormone replacement therapy and chemoprevention. Climacteric 2012;15:250–5

Gender-specific characteristics of cardiovascular disease in women

  • Stramba-Badiale M, Fox KM, Priori SG, et al. Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology. Eur Heart J 2006;27:994–1005
  • Collins P, Rosano G, Casey C, et al. Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists. Climacteric 2007;10: 508–26
  • , Executive Writing CommitteeMosca 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;123:1243–62

Postmenopausal hormones and coronary artery disease

  • Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605–13
  • Hsia J, Langer RD, Manson JE, et al. Conjugated equine estrogens and coronary heart disease: the Women's Health Initiative. Arch Intern Med 2006;166:357–65
  • Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Women's Health 2006;15:35–44
  • Prentice RL, Langer RD, Stefanick ML, et al. Combined analysis of Women's Health Initiative observational and clinical trial data on postmenopausal hormone treatment and cardiovascular disease. Am J Epidemiol 2006;163:589–99
  • Salpeter SR, Walsh JM, Greyber E, Salpeter EE. Coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med 2006;21:363–6
  • Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465–77
  • Salpeter SR, Cheng J, Thabane L, Buckley NS, Salpeter EE. Bayesian meta-analysis of hormone therapy and mortality in younger women. Ann Intern Med 2009;122:1016–22
  • Stevenson JC, Hodis HN, Pickar JH, Lobo RA. Coronary heart disease and menopause management: the swinging pendulum of HRT. Atherosclerosis 2009;207:336–40
  • Toh S, Hernández-Días S, Logan R, Rossouw JE, Hernán MA. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: does the increased risk ever disappear? A randomized trial. Ann Intern Med 2010;152:211–17
  • Hodis HN, Collins P, Mack WJ, Schierbeck LL. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric 2012;15:217–28

Coagulation

Stroke

  • Viscoli CM, Brass LM, Kernan WN, et al. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med 2001; 345:1243–9
  • Wassertheil-Smoller S, Hendrix S, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 2003; 289:2673–84
  • Bath PM, Gray LJ. Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ 2005;330:342
  • Arana A, Varas C, Gonzalez-Perez A, et al. Hormone therapy and cerebrovascular events: a population-based nested case-control study. Menopause 2006;13:1–7
  • Hendrix SL, Wassertheil-Smoller S, Johnson KC, et al. Effects of conjugated equine estrogen on stroke in the Women’s Health Initiative. Circulation 2006;113:2425–34
  • Grodstein F, Manson JE, Stampfer MJ, Rexrode K. Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy. Arch Intern Med 2008; 168:861–6
  • Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ 2010;340:c2519
  • Lobo RA, Clarkson TB. Different mechanisms for benefit and risk of coronary heart disease and stroke in early postmenopausal women: a hypothetical explanation. Menopause 2011;18:237–40
  • Henderson VW, Lobo RA. Hormone therapy and the risk of stroke: perspectives 10 years after the Women’s Health Initiative trials. Climacteric 2012;15:229–34

Other neurological disorders

  • Harden CL, Herzog AG, Nikolov BG, et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia 2006;47:1447–51
  • Freeman EW, Sammel MD, Lin H, Gracia CR, Kapoor S. Symptoms in the menopausal transition: hormone and behavioral correlates. Obstet Gynecol 2008;111:127–36
  • MacGregor EA. Estrogen replacement and migraine. Maturitas 2009;63:51–5
  • Simon KC, Chen H, Gao X, Schwarzschild MA, Ascherio A. Reproductive factors, exogenous estrogen use, and risk of Parkinson’s disease. Mov Disord 2009;24:1359–65
  • El-Etr M, Ghoumari A, Sitruk-Ware R, Schumacher M. Hormonal influences in multiple sclerosis: new therapeutic benefits for steroids. Maturitas 2011;68:47–51

Cognition and cognitive aging

  • Resnick SM, Maki PM, Rapp SR, et al. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinol Metab 2006;91:1802–10
  • Maki PM, Gast MJ, Vieweg A, Burriss SW, Yaffe K. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial. Neurology 2007;69:1322–30
  • Lethaby A, Hogervorst E, Richards M, Yesufu A, Yaffe K. Hormone replacement therapy for cognitive function in postmenopausal women. Cochrane Database Syst Rev 2008;1:CD003122
  • Greendale GA, Huang M-H, Wight RG, et al. Effects of the menopause transition and hormone use on cognitive performance in midlife women. Neurology 2009;72:1850–7
  • Resnick SM, Espeland MA, An Y, et al. Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy. J Clin Endocrinol Metab 2009;94:4152–61
  • Henderson VW. Action of estrogens in the aging brain: dementia and cognitive aging. Biochim Biophys Acta 2010;1800:1077–83
  • Henderson VW. Gonadal hormones and cognitive aging: a midlife perspective. Womens Health (Lond Engl) 2011;7:81–93
  • Maki PM, Henderson VW. Hormone therapy, dementia, and cognition: the Women’s Health Initiative 10 years on. Climacteric 2012;15:256–62

Alzheimer's disease and other dementing disorders

  • Mulnard RA, Cotman CW, Kawas C, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. JAMA 2000;283:1007–15
  • Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291:2947–58
  • Henderson VW, Benke KS, Green RC, Cupples LA, Farrer LA. Postmenopausal hormone therapy and Alzheimer’s disease risk: interaction with age. J Neurol Neurosurg Psychiatry 2005;76:103–5
  • Hogervorst E, Yaffe K, Richards M, Huppert FA. Hormone replacement therapy to maintain cognitive function in women with dementia. Cochrane Database of Syst Rev 2009;1:CD003799
  • Whitmer RA, Quesenberry CP, Zhou J, Yaffe K. Timing of hormone therapy and dementia: The critical window theory revisited. Ann Neurol 2011;69:163–9
  • Henderson VW. Action of estrogens in the aging brain: dementia and cognitive aging. Biochim Biophys Acta 2010;1800:1077–83
  • Wharton W, Baker LD, Gleason CE, et al. Short-term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer’s disease: results of a randomized controlled trial. J Alzheimers Dis 2011;26:495–505
  • Shao H, Breitner JCS, Whitmer RA, et al. Hormone therapy and AD dementia: new findings from the Cache County study. Neurology 2012;79:1846–52

Depression

  • Schmidt PJ, Haq N, Rubinow DR. A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women. Am J Psychiatry 2004;161:2238–44
  • Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 2006;63:375–82
  • Ryan J, Burger HG, Szoeke C, et al. A prospective study of the association between endogenous hormones and depressive symptoms in postmenopausal women. Menopause 2009;6:509–17
  • Bromberger JT, Schott LL, Kravitz HM, et al. Longitudinal change in reproductive hormones and depressive symptoms across the menopausal transition: results from the Study of Women’s Health Across the Nation (SWAN). Arch Gen Psychiatry 2010;67: 598–607
  • Maki PM, Freeman EW, Greendale GA, et al. Summary of the National Institute on Aging-sponsored conference on depressive symptoms and cognitive complaints in the menopausal transition. Menopause 2010;17:815–22
  • Soares CN, Frey BN. Is there a role for estrogen in treating depression during menopause?J Psychiatry Neurosci 2010;35:E6–7
  • Studd J, Nappi RE. Reproductive depression. Gynecol Endocrinol 2012;28(Suppl 1):42–5
  • Yalamanchili V, Gallagher JC. Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause 2012;19:697–703

Osteoporosis

General

  • Genazzani AR, Gambacciani M, Schneider HP, Christiansen C;International Menopause Society Expert Workshop. Postmenopausal osteoporosis: therapeutic options. Climacteric 2005;8: 99–109
  • Lewiecki EM. Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis. J Womens Health (Larchmt) 2009;18:1615–26
  • Lyritis GP, Georgoulas T, Zafeiris CP. Bone anabolic versus bone anticatabolic treatment of postmenopausal osteoporosis. Ann NY Acad Sci 2010;1205:277–83
  • Management of osteoporosis in postmenopausal women:2010 position statement of The North American Menopause Society. Menopause 2010;17:25–54
  • Trémollières FA, Pouillès JM, Drewniak N, et al. Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool. J Bone Miner Res 2010;25:1002–9
  • Gallagher JC, Levine JP. Preventing osteoporosis in symptomatic postmenopausal women. Menopause 2011;18:109–18

MHT

  • 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;290:1729–38
  • 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;291:1701–12
  • Bagger YZ, Tanko LB, Alexandersen P, et al. Two to three years of hormone replacement therapy in healthy women have long-term prevention effects on bone mass and osteoporotic fractures: the PERF study. Bone 2004;34:728–31
  • Lindsay R,Gallagher JC, Kleerekoper M, et al. Bone response to treatment with lower dosages of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women. Osteoporos Int 2005;4:372–9
  • Stevenson JC; International Consensus Group on HRT and Regulatory Issues. HRT, osteoporosis and regulatory authorities Quis custodiet ipsos custodes?Hum Reprod 2006;21:1668–71
  • Cummings SR, Ettinger B, Delmas PD, et al. for the LIFT Trial Investigators. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697–708
  • 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;92:1045–52
  • de Villiers TJ, Stevenson JC. The WHI: the effect of hormone replacement therapy on fracture prevention. Climacteric 2012;15:263–6

Calcium and vitamin D

  • Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354:669–83
  • Boonen S, Lips P, Bouillon R, et al. Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: evidence from a comparative meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2007;92: 1415–23
  • Rizzoli R, Boonen S, Brandi ML, et al. The role of calcium and vitamin D in the management of osteoporosis. Bone 2008;42: 246–9
  • Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. Br Med J 2009; 339:b3692
  • Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691
  • The DIPART (vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 2010;340:b5463

SERMs

  • 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;87:3609–17
  • Ensrud KE, Stock JL, Barrett-Connor E, et al. Effects of raloxifene on fracture risk in postmenopausal women: the Raloxifene Use for the Heart Trial. J Bone Miner Res 2008;23:112–20
  • 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;23:1923–34
  • Goldstein SR, Duvernoy CS, Calaf J, et al. Raloxifene use in clinical practice: efficacy and safety. Menopause 2009;16:413–21

Denosumab

  • Cummings SR, Martin S, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–65

Skin, joints and cartilage

  • 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;54:3194–204
  • Holinka CF, Christiansen C, Tian XW, Ausmanas MK. Ethnic differences in levels of bone and cartilage biomarkers and hormonal responsiveness in nine groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study. Climacteric 2008;11: 44–54
  • Calleja-Agius J, Brincat MP. Effects of hormone replacement therapy on connective tissue: why is this important?Best Pract Res Clin Obstet Gynaecol 2009;23:121
  • Calleja-Agius J, Muscat-Baron Y, Brincat MP. Estrogens and the intervertebral disc. Menopause Int 2009;15:127–30
  • Pullerits R, d’Elia HF, Tarkowski A, Carlsten H. The decrease of soluble RAGE levels in rheumatoid arthritis patients following hormone replacement therapy is associated with increased bone mineral density and diminished bone/cartilage turnover: a randomized controlled trial. Rheumatology (Oxford) 2009;48:785–90
  • Sniekers YH, Weinans H, van Osch GJ, van Leeuwen JP. Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis. Arthritis Res Ther 2010;12:R182

New hormonal products

  • Pinkerton JV, Utian WH, Constantine GD, Olivier S, Pickar JH. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: a randomized, controlled trial. Menopause 2009;16:1116–24
  • de Villiers TJ. Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis. Climacteric 2010; 13:210–18
  • Portman DJ, Bachmann GA, Simon JA; the Ospemifene Study Group. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause 2013 Jan 28. Epub ahead of print

Postmenopausal vaginal atrophy

  • Suckling J, Kennedy R, Lethaby A, Roberts H. Local estrogen therapy for vaginal atrophy in post menopausal women. Cochrane Database Syst Rev 2006 Issue 4 CD 001500
  • Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause 2010;17:194–203
  • Sturdee DW, Panay N, on behalf of the IMS Writing Group. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric 2010;13:509–22
  • Ulrich LS, Naessen T, Elia D, Goldstein JA, Eugster-Hausmann M. VAG-1748 trial investigators. Endometrial safety of ultra-low-dose Vagifem 10 μg in postmenopausal women with vaginal atrophy. Climacteric 2010;13:228–37
  • Labrie F, Archer DF, Bouchard C, et al. Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia. Climacteric 2011;14:282–8
  • Nappi RE, Kokot-Kierepa M. Vaginal Health: Insights, Views & Attitudes (VIVA) – results from an international survey. Climacteric 2012;15:36–44

So-called ‘bioidentical’ or ‘natural’ hormones

Non-hormonal therapy

  • Nedrow A, Miller J, Walker M, et al. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med 2006;166:1453–65
  • Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057–71
  • Sassarini J, Lumsden MA. Hot flushes: are there effective alternatives to estrogen?Menopause Int 2010;16:81–8

Endometrial safety and bleeding

  • Wiederpass E. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst 1999; 91:1131–7
  • Anderson GL, Judd HL, Kaunitz AM, et al. The effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 2003:290:1739–48
  • Lethaby A, Suckling J, Barlow DH, et al. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004; 3:CD000402
  • Million Women Study Collaborators. Endometrial cancer and hormone replacement therapy in the Million Women Study. Lancet 2005;365:1543–51
  • Langer RD, Landgren B-M, Rymer J, Helmond FA:OPAL investigators. Effects of tibolone and continuous combined conjugated equine estrogen/medroxyprogesterone acetate on the endometrium and vaginal bleeding: results of the OPAL study. Am J Obstet Gynecol 2006;195:1320–7
  • Sturdee DW, Archer DF, Rakov V, Lang E,on behalf of the CHOICE Investigators. Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women. Climacteric 2008;11:63–73
  • Bednarek PH, Jenesn JT. Safety, efficacy and patient acceptability of the contraceptive and non-contraceptive uses of the LNG-IUS. Int J Women Hlth 2009;1:45–58
  • Chin J, Konje JC, Hickey M. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database Syst Rev 2009;4 : CD 007245

Androgens

  • Zumoff B, Strain GW, Miller LK, Rosner W. Twenty-four hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab 1995;80: 1429–30
  • Braunstein G, Shifren J, Simon J, Lucas J, Rodenberg C, Watts NB. Testosterone patches for the treatment of low sexual desire in surgically menopausal women. Proceedings of the 14th Annual Meeting of the North American Menopause Society, 2003
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  • Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90: 3847–53
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  • Warnock JK, Swanson SG, Borel RW, et al. for ESTRATEST Clinical Study Group. Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women. Menopause 2005;12:374–84
  • Burger HG, Papalia M. A clinical update on female androgen insufficiency – testosterone testing and treatment in women presenting with low sexual desire. Sexual Health 2006;3:73–78
  • Shifren J, Davis SR, Moreau M, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 study. Menopause 2006;13:770–9
  • Davis SR, Moreau M, Kroll R, et al. Testosterone for low libido in menopausal women not taking estrogen therapy. N Engl J Med 2008;359:2005–17
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  • Perrone AM, Cerpolini S, Maria Salfi NC, et al. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med 2009;6:3193–200
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  • Panjari N, Davis SR. DHEA for postmenopausal women: a review of the evidence. Maturitas 2010;66:172–9
  • Davis SR. Cardiovascular and cancer safety of testosterone in women. Curr Opin Endocrinol Diabetes Obes 2011;18:198–203
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Urogynecology

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  • 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 Committee. Int Urogynecol J Pelvic Floor Dysfunct 2001;12:15–20
  • Hendrix SL, Cochrane BR, Nygaard IE, et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA 2005; 293:935–48
  • Andersson KE, Chapple CR, Cardozo L, et al. Pharmacological treatment of urinary incontinence. In Abrams P, Cardozo L, Khoury S, Wein A, eds. Incontinence. Paris: Health Publications Ltd, 2009:633–99
  • Cody JD, Richardson K, Moehrer B, Hextall A, Glazener CMA. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database of Systematic Reviews 2009, Issue 4 . Art. No: CD001405

Attitudes to sexuality in the menopause

  • Genazzani AR, Gambacciani M, Simoncini T. Menopause and aging, quality of life and sexuality. IMS Statement following 6th IMS Workshop, Pisa, December2006. Climacteric 2007;10:88–96
  • Hayes RD, Dennerstein L, Bennett CM, et al. Risk factors for female sexual dysfunction in the general population: exploring factors associated with low sexual function and sexual distress. J Sex Med 2008;5:1681–93
  • Nappi RE, Polatti F. The use of estrogen therapy in women's sexual function. J Sex Med 2009;6:603–16
  • Nappi RE, Davis SR. The use of hormone therapy for the maintenance of urogynecological and sexual health post WHI. Climacteric 2012;5:267–74

Influence of methodology and epidemiology on perception of HRT

  • Knobe J. Intentional action and side effects in ordinary language. Analysis 2003;63:190–3
  • Schwartz LM, Woloshin S. The media matter: a call for straightforward medical reporting. Ann Intern Med 2004;140:226–8
  • Kolata G. Health risk to older women is seen in hormone therapy. The New York Times, April4, 2007
  • Specter M. Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives. London: Duckworth Overlook Press, 2009
  • Bluming AZ, Tavris C. Hormone replacement therapy: real concerns and false alarms. Cancer J 2009;15:93–104
  • Brown S. Shock, terror and controversy: how the media reacted to the Women’s Health Initiative. Climacteric 2012;15:275–80

Further reading

  • Special issue of Climacteric: The Women's Health Initiative – A decade of progress. June 2012;15:205–94

Recent recommendations by other societies

  • Gompel A, Rozenberg S, Barlow DH; EMAS board members. The EMAS 2008 update on clinical recommendations on postmenopausal hormone replacement therapy. Maturitas 2008;61: 227–32
  • Santen RJ, Allred DC, Ardoin SP, et al. Executive summary: Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010;95(Suppl 1):s1–66
  • North American Menopause Society. The 2012 hormone therapy position statement of The North American Menopause Society. Menopause 2012;19:257–71

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