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Review

Safety and benefit considerations for menopausal hormone therapy

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Pages 941-954 | Received 31 Mar 2017, Accepted 13 Jun 2017, Published online: 30 Jun 2017

References

  • North American Menopause Society. The 2012 hormone therapy position statement of the North American Menopause Society. Menopause. 2012;19(3):257–271.
  • Lobo RA, Pickar JH, Stevenson JC, et al. Back to the future: hormone replacement therapy as part of a prevention strategy for women at the onset of menopause. Atherosclerosis. 2016;254:296–304.
  • Guidelines for counseling postmenopausal women about preventive hormone therapy. American College of Physicians. Ann Intern Med. 1992;117(12):1038–1041.
  • Lobo RA, Whitehead M. Too much of a good thing? Use of progestogens in the menopause: an international consensus statement. Fertil Steril. 1989;51(2):229–231.
  • 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(7):605–613.
  • Design of the Women’s Health Initiative clinical trial and observational study. The Women’s Health Initiative Study Group. Control Clin Trials. 1998;19(1):61–109.
  • 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(3):321–333.
  • 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(14):1701–1712.
  • Stuenkel CA, Gass ML, Manson JE, et al. A decade after the Women’s Health Initiative–the experts do agree. Fertil Steril. 2012;98(2):313–314.
  • Hodis HN, Mack WJ, Henderson VW, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374(13):1221–1231.
  • Henderson VW, St John JA, Hodis HN, et al. Cognitive effects of estradiol after menopause: a randomized trial of the timing hypothesis. Neurology. 2016;87(7):699–708.
  • Harman SM, Black DM, Naftolin F, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014;161(4):249–260.
  • Bhavnani BR. Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. Proc Soc Exp Biol Med. 1998;217(1):6–16.
  • Jordan VC, Mittal S, Gosden B, et al. Structure-activity relationships of estrogens. Environ Health Perspect. 1985;61:97–110.
  • Stanczyk FZ, Hapgood JP, Winer S, et al. Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects. Endocr Rev. 2013;34(2):171–208.
  • Kling JM, Lahr BA, Bailey KR, et al. Endothelial function in women of the Kronos Early Estrogen Prevention Study. Climacteric. 2015;18:187–197.
  • Canonico M, Fournier A, Carcaillon L, et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: results from the E3N cohort study. Arterioscler Thromb Vasc Biol. 2010;30(2):340–345.
  • Renoux C, Dell’Aniello S, Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J Thromb Haemost. 2010;8(5):979–986.
  • Renoux C, Dell’Aniello S, Garbe E, et al. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
  • Lokkegaard E, Andreasen AH, Jacobsen RK, et al. Hormone therapy and risk of myocardial infarction: a national register study. Eur Heart J. 2008;29(21):2660–2668.
  • Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–845.
  • Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health. 2006;15(1):35–44.
  • Canonico M, Plu B, Lowe GD, et al. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. BMJ. 2008;336(7655):1227–1231.
  • Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013;310(13):1353–1368.
  • Shufelt CL, Merz CN, Prentice RL, et al. Hormone therapy dose, formulation, route of delivery, and risk of cardiovascular events in women: findings from the Women’s Health Initiative Observational Study. Menopause. 2014;21(3):260–266.
  • Smith NL, Blondon M, Wiggins KL, et al. Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA Intern Med. 2014;174(1):25–31.
  • Mikkola TS, Tuomikoski P, Lyytinen H, et al. Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause. 2015;22(9):976–983.
  • 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.
  • Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349(6):523–534.
  • Viscoli CM, Brass LM, Kernan WN, et al. A clinical trial of estrogen-replacement therapy after ischemic stroke. N Engl J Med. 2001;345(17):1243–1249.
  • Chlebowski RT, Kuller LH, Prentice RL, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 2009;360(6):573–587.
  • Langer RD. The evidence base for HRT: what can we believe? Climacteric. 2017;20(2):91–96.
  • Chlebowski RT, Rohan TE, Manson JE, et al. Breast cancer after use of estrogen plus progestin and estrogen alone: analyses of data from 2 women’s health initiative randomized clinical trials. JAMA Oncol. 2015;1(3):296–305.
  • 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(1):144–156.
  • Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107(1):103–111.
  • Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estrogen-only therapy. Obstet Gynecol. 2006;108(6):1354–1360.
  • Lyytinen HK, Dyba T, Ylikorkala O, et al. A case-control study on hormone therapy as a risk factor for breast cancer in Finland: intrauterine system carries a risk as well. Int J Cancer. 2010;126(2):483–489.
  • Mikkola TS, Savolainen-Peltonen H, Tuomikoski P, et al. Reduced risk of breast cancer mortality in women using postmenopausal hormone therapy: a Finnish nationwide comparative study. Menopause. 2016;23(11):1199–1203.
  • Cordina-Duverger E, Truong T, Anger A, et al. Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS One. 2013;8(11):e78016.
  • Fournier A, Berrino F, Riboli E, et al. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer. 2005;114(3):448–454.
  • Espeland MA, Rapp SR, Shumaker SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004;291(24):2959–2968.
  • Rapp SR, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2663–2672.
  • Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651–2662.
  • 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(24):2947–2958.
  • 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(11):4152–4161.
  • 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(5):1802–1810.
  • Gleason CE, Dowling NM, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-Cognitive and Affective Study. Plos Med. 2015;12(6):e1001833; discussion e1001833.
  • Yaffe K, Vittinghoff E, Ensrud KE, et al. Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life. Arch Neurol. 2006;63(7):945–950.
  • Tierney MC, Oh P, Moineddin R, et al. A randomized double-blind trial of the effects of hormone therapy on delayed verbal recall in older women. Psychoneuroendocrinology. 2009;34(7):1065–1074.
  • Maki PM, Gast MJ, Vieweg AJ, et al. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial. Neurology. 2007;69(13):1322–1330.
  • Maki PM, Rubin LH, Fornelli D, et al. Effects of botanicals and combined hormone therapy on cognition in postmenopausal women. Menopause. 2009;16(6):1167–1177.
  • Wroolie TE, Kenna HA, Williams KE, et al. Cognitive effects of hormone therapy continuation or discontinuation in a sample of women at risk for Alzheimer disease. Am J Geriatr Psychiatry. 2015;23(11):1117–1126.
  • Hogervorst E, Bandelow S. Sex steroids to maintain cognitive function in women after the menopause: a meta-analyses of treatment trials. Maturitas. 2010;66(1):56–71.
  • LeBlanc ES, Janowsky J, Chan BK, et al. Hormone replacement therapy and cognition: systematic review and meta-analysis. JAMA. 2001;285(11):1489–1499.
  • Imtiaz B, Tuppurainen M, Rikkonen T, et al. Postmenopausal hormone therapy and Alzheimer disease: a prospective cohort study. Neurology. 2017;88(11):1062–1068.
  • Schmidt PJ, Nieman L, Danaceau MA, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000;193(2):414–420.
  • Soares CN, Almeida OP, Joffe H, et al. Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry. 2001;58(6):529–534.
  • Rasgon NL, Dunkin J, Fairbanks L, et al. Estrogen and response to sertraline in postmenopausal women with major depressive disorder: a pilot study. J Psychiatr Res. 2007;41(3–4):338–343.
  • Schmidt PJ, Ben Dor R, Martinez PE, et al. Effects of estradiol withdrawal on mood in women with past perimenopausal depression: a randomized clinical trial. JAMA Psychiatry. 2015;72(7):714–726.
  • \Palacios S, Mejia A. Progestogen safety and tolerance in hormonal replacement therapy. Expert Opin Drug Saf. 2016;15(11):1515–1525.
  • Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA. 1996;275(5):370–375.
  • Chlebowski RT, Anderson GL, Sarto GE, et al. Continuous combined estrogen plus progestin and endometrial cancer: the Women’s Health Initiative randomized trial. J Natl Cancer Inst. 2016;108(3):dvj350.
  • Beral V, Bull D, Reeves G. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005;365(9470):1543–1551.
  • Allen NE, Tsilidis KK, Key TJ, et al. Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition. Am J Epidemiol. 2010;172(12):1394–1403.
  • Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. JAMA. 1995;273(3):199–208.
  • Stute P, Neulen J, Wildt L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. 2016;19(4):316–328.
  • Archer DF, Lobo R, Kagan R, et al. REPLENISH Trial: endometrial safety with a 17β-estradiol and progesterone combination (TX-001HR) in postmenopausal women with vasomotor symptoms. Paper presented at: ENDO, 2017; Orlando, FL.
  • Steinkellner AR, Denison SE, Eldridge SL, et al. A decade of postmenopausal hormone therapy prescribing in the United States: long-term effects of the Women’s Health Initiative. Menopause. 2012;19(6):616–621.
  • MacLennan AH, Gill TK, Broadbent JL, et al. Continuing decline in hormone therapy use: population trends over 17 years. Climacteric. 2009;12(2):122–130.
  • Committee on Gynecologic Practice and the American Society for Reproductive Medicine Practice Committee. Compounded bioidentical menopausal hormone therapy. Committee Opinion No. 532. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2012;120:411–415.
  • Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause. 2004;11(3):356–367.
  • Pinkerton J, Santoro N. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women. Menopause. 2015;22(9):926–936.
  • Gass ML, Stuenkel C, Utian WH, et al. Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey. Menopause. 2015;22(9):926–936.
  • de Villiers TJ, Hall JE, Pinkerton JV, et al. Revised global consensus statement on menopausal hormone therapy. Climacteric. 2016;19(4):313–315.
  • Pinkerton JV, Pickar JH. Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy. Menopause. 2016;23(2):215–223.
  • Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metabol. 2015;100(11):3975–4011.
  • Eden JA, Hacker NF, Fortune M. Three cases of endometrial cancer associated with “bioidentical” hormone replacement therapy. Med J Aust. 2007;187(4):244–245.
  • Davis R, Batur P, Thacker HL. Risks and effectiveness of compounded bioidentical hormone therapy: a case series. J Womens Health (Larchmt). 2014;23(8):642–648.
  • Dezman VL, Gersak MZ, Gersak K. Two case of atypical endometrial hyperplasia associated with “bioidentical” hormone replacement therapy: IGCS-0084 uterine cancer, including sarcoma. Int J Gynecol Cancer. 2015;25(Suppl 1):71.
  • Saarikoski S, Yliskoski M, Penttila I. Sequential use of norethisterone and natural progesterone in pre-menopausal bleeding disorders. Maturitas. 1990;12(2):89–97.
  • Casanova G, Radavelli S, Lhullier F, et al. Effects of nonoral estradiol-micronized progesterone or low-dose oral estradiol-drospirenone therapy on metabolic variables and markers of endothelial function in early postmenopause. Fertil Steril. 2009;92(2):605–612.
  • Rosano GM, Webb CM, Chierchia S, et al. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol. 2000;36(7):2154–2159.
  • Murkes D, Lalitkumar PG, Leifland K, et al. Percutaneous estradiol/oral micronized progesterone has less-adverse effects and different gene regulations than oral conjugated equine estrogens/medroxyprogesterone acetate in the breasts of healthy women in vivo. Gynecol Endocrinol. 2012;28(Suppl 2):12–15.
  • 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. J Clin Oncol. 2008;26(8):1260–1268.
  • Fournier A, Mesrine S, Dossus L, et al. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat. 2014;145(2):535–543.
  • Sherwin BB, Grigorova M. Differential effects of estrogen and micronized progesterone or medroxyprogesterone acetate on cognition in postmenopausal women. Fertil Steril. 2011;96(2):399–403.
  • Fitzpatrick LA, Pace C, Wiita B. Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med. 2000;9(4):381–387.
  • Ryan N, Rosner A. Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women. Clin Ther. 2001;23(7):1099–1115.
  • Files JA, Miller VM, Cha SS, et al. Effects of different hormone therapies on breast pain in recently postmenopausal women: findings from the Mayo Clinic KEEPS breast pain ancillary study. Jwomens Health (Larchmt). 2014;23(10):801–805.
  • Greendale GA, Reboussin BA, Hogan P, et al. Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial. Obstet Gynecol. 1998;92(6):982–988.
  • Archer DF, Thorneycroft IH, Foegh M, et al. Long-term safety of drospirenone-estradiol for hormone therapy: a randomized, double-blind, multicenter trial. Menopause. 2005;12(6):716–727.
  • Schurmann R, Holler T, Benda N. Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens. Climacteric. 2004;7(2):189–196.
  • Pickar JH, Yeh IT, Bachmann G, et al. Endometrial effects of a tissue selective estrogen complex (TSEC) containing bazedoxifene/conjugated estrogens as a menopausal therapy. Fertil Steril. 2009;92(3):1018–1024.
  • Stovall DW, Utian W, Gass M, et al. The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety. Menopause. 2007;14(3):510–517.
  • Pinkerton JV, Harvey JA, Lindsay R, et al. Effects of bazedoxifene/conjugated estrogens on the endometrium and bone: a randomized trial. J Clin Endocrinol Metab. 2014;99(2):E189–E198.
  • Komm BS, Thompson JR, Mirkin S. Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. Climacteric. 2015;18(4):503–511.
  • Skouby SO, Pan K, Thompson JR, et al. Effects of conjugated estrogens/bazedoxifene on lipid and coagulation variables: a randomized placebo- and active-controlled trial. Menopause. 2015;22(6):640–649.
  • Pinkerton JV, Harvey JA, Pan K, et al. Breast effects of bazedoxifene-conjugated estrogens: a randomized controlled trial. Obstet Gynecol. 2013;121(5):959–968.
  • Harvey JA, Pinkerton JV, Baracat EC, et al. Breast density changes in a randomized controlled trial evaluating bazedoxifene/conjugated estrogens. Menopause. 2013;20(2):138–145.
  • Kagan R, Williams RS, Pan K, et al. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens (BZA/CE) for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women. Menopause. 2010;17(2):281–289.
  • Tiblone 2.5 mg tablets. Summary of Product Characteristics. Mercury pharmaceuticals. 2016.
  • Hodis HN, Mack WJ, Lobo RA, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;135(11):939–953.
  • Hodis HN, Mack WJ, Azen SP, et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. N Engl J Med. 2003;349(6):535–545.
  • Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women’s Health Initiative. Obstet Gynecol. 2005;105(5 Pt 1):1063–1073.
  • 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(13):1465–1477.
  • Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356(25):2591–2602.
  • Carrasquilla GD, Chiavenna C, Bottai M, et al. The association between menopausal hormone therapy and coronary heart disease depends on timing of initiation in relation to menopause onset. Results based on pooled individual participant data from the Combined Cohorts of Menopausal Women-Studies of Register Based Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) study. Menopause. 2015;22(12):1373.
  • Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2015;10(3):Cd002229.
  • Salpeter SR, Walsh JM, Greyber E, et al. Brief report: coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J Gen Intern Med. 2006;21(4):363–366.
  • Espeland MA, Shumaker SA, Leng I, et al. Long-term effects on cognitive function of postmenopausal hormone therapy prescribed to women aged 50 to 55 years. JAMA Intern Med. 2013;173(15):1429–1436.
  • Whitmer RA, Quesenberry CP, Zhou J, et al. Timing of hormone therapy and dementia: the critical window theory revisited. Ann Neurol. 2011;69(1):163–169.
  • Shao H, Breitner JC, Whitmer RA, et al. Hormone therapy and Alzheimer disease dementia: new findings from the Cache County Study. Neurology. 2012;79(18):1846–1852.
  • Henderson VW, Benke KS, Green RC, et al. Postmenopausal hormone therapy and Alzheimer’s disease risk: interaction with age. J Neurol Neurosurg Psychiatry. 2005;76(1):103–105.
  • Lipold LD, Batur P, Kagan R. Is there a time limit for systemic menopausal hormone therapy? Cleve Clin J Med. 2016;83(8):605–612.
  • Faubion SS, Kuhle CL, Shuster LT, et al. Long-term health consequences of premature or early menopause and considerations for management. Climacteric. 2015;18(4):483–491.
  • Fenton AJ. Premature ovarian insufficiency: pathogenesis and management. J Midlife Health. 2015;6(4):147–153.
  • The North American Menopause Society. MenoPro Mobile App. Clinicians and women working together to personalize treatment decisions. cited 2017 February. Available from: https://www.menopause.org/for-professionals/-i-menopro-i-mobile-app
  • Management of menopausal symptoms. Practice bulletin no. 141. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2014;123(1):202–216.
  • The North American Menopause Society. 3rd Utian Translational Science Symposium. A conversation about hormone therapy: is there an appropriate dose, route, and duration of use? Paper presented at: NAMS Annual Meeting, 2016. Orlando, FL.
  • Manson JE. Current recommendations: what is the clinician to do? Fertil Steril. 2014;101(4):916–921.
  • Ockene JK, Barad DH, Cochrane BB, et al. Symptom experience after discontinuing use of estrogen plus progestin. JAMA. 2005;294(2):183–193.
  • Marjoribanks J, Farquhar C, Roberts H, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017;1:Cd004143.
  • North American Menopause Society. The North American Menopause Society statement on continuing use of systemic hormone therapy after age 65. Menopause. 2015;22(7):693.
  • Mikkola TS, Tuomikoski P, Lyytinen H, et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab. 2015;100(12):4588–4594.

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