Zusammenfassung
Die Hormonersatztherapie (HRT) bei peri- und postmenopausalen Frauen ist die effektivste Behandlung klimakterischer Beschwerden und gehört zu den am häufigsten eingesetzten endokrinen Therapien. Bei der Verordnung sind Nutzen und Risiken gegeneinander abzuwägen. Zu den potenziellen Risiken gehört das erhöhte Krebsrisiko. Risikomodifikationen betreffen überwiegend das Mamma-, das Endometrium- und das Ovarialkarzinom. Eine HRT kann das Brustkrebsrisiko erhöhen, abhängig von der Zusammensetzung der eingesetzten Präparate und der Anwendungsdauer. Eine HRT mit Östrogenen und Gestagenen (EPT) erhöht das Risiko stärker als eine Östrogenmonotherapie (ET). Bei einer EPT sind Anwendungszeiten von ca. 5 Jahren erforderlich, um eine geringe Risikosteigerung nachzuweisen. Bei der ET ist die Risikosteigerung erst nach längeren Anwendungszeiten nachweisbar. Eine ET kann bei postmenopausalen Frauen zu einem erhöhten Endometriumkarzinomrisiko führen. Daher soll bei nichthysterektomierten Frauen grundsätzlich nur eine EPT mit ausreichend langer Gestagenanwendung erfolgen. Eine Anwendungszeit einer EPT bis zu 5 Jahren erhöht das Endometriumkarzinomrisiko nicht. Längerfristige sequenzielle Therapien können zu einer Erhöhung des Endometriumkarzinomrisikos führen. Für die mehr als fünfjährige kontinuierlich kombinierte EPT sind die Studienergebnisse diesbezüglich kontrovers. Der Zusammenhang zwischen einer HRT und dem Ovarialkarzinomrisiko wurde in der Vergangenheit kontrovers beurteilt. Eine jüngere Metaanalyse zeigt, dass eine HRT (ET bzw. EPT) das Risiko erhöhen kann. Aufgrund der geringen Inzidenz des Ovarialkarzinoms ist das absolute Risiko relativ gering. Die differenzierte Aufklärung der Patientin über o. a. Risiken ist vor Anwendung einer HRT zur Behandlung klimakterischer Beschwerden zu beachten. Sie ist in die Entscheidungsfindung miteinzubeziehen und bei der Durchführung einer HRT zu berücksichtigen.
Abstract
Hormone replacement therapy (HRT) is the most efficient treatment for climacteric symptoms and is one of the most frequently prescribed endocrine therapies. Before prescription of any form of HRT, the associated risks and benefits should be weighed up against each other. Potential risks include breast, endometrial, and ovarian cancer. HRT may increase the risk of breast cancer, depending on the duration of treatment and the specific HRT preparation. Combined HRT with estrogens and progestins (EPT) is associated with a higher risk of breast cancer than estrogen-only preparations (ET). Specifically, EPT increases the risk of breast cancer after around 5 years of treatment, whereas ET shows this effect only after longer treatment durations. ET may increase the endometrial cancer risk in postmenopausal women. Non-hysterectomized women should therefore only be treated with EPT of sufficient dosage and duration. Application of EPT for up to 5 years does not increase the endometrial cancer risk. Long-term sequential EPT regimens may increase the endometrial cancer risk. Study results on the use of continually combined EPT for over 5 years are controversial. The association between HRT and ovarian cancer risk is uncertain. However, a recent meta-analysis demonstrated that HRT (ET and EPT) may increase the ovarian cancer risk. Due to the low incidence of this disease, the absolute risk is low. Before the use of any form of HRT, women should be appropriately informed about the abovenamed risks and benefits of this treatment for climacteric symptoms. These risks have to be included in the decision for or against HRT, and have to be reconsidered during the course of long-term use of HRT.
Literatur
DGGG (2019) Peri- and Postmenopause—Diagnosis and Interventions. Guideline of the German Society of Gynecology and Obstetrics (S‑3 Level, AWMF Registry No. 015-062, June 2019). http://www.awmf.org/leitlinien/detail/ll/015-062.html. Zugegriffen: 31. Juli 2019
Buchholz S, Ortmann O (2014) Weitere Tumoren und Endokrinium. In: Leidenberger F, Strowitzki T, Ortmann O (Hrsg) Klinische Endokrinologie für Frauenärzte. Springer, Berlin
Mills PK, Beeson WL, Phillips RL, Fraser GE (1989) Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists. Cancer 64:591–597
Colditz GA, Stampfer MJ, Willett WC et al (1992) Type of postmenopausal hormone use and risk of breast cancer: 12-year follow-up from the Nurses’ Health Study. Cancer Causes Control 3:433–439
Folso AR, Mink PJ, Sellers TA et al (1995) Hormonal replacement therapy and morbidity and mortality in a prospective study of postmenopausal women. Am J Public Health 85:1128–1132
Schuurman AG, van den Brandt PA, Goldbohm RA (1995) Exogenous hormone use and the risk of postmenopausal breast cancer: results from The Netherlands Cohort Study. Cancer Causes Control 6:416–424
Willis DB, Calle EE, Miracle-McMahill HL, Heath CW Jr (1996) Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States. Cancer Causes Control 7:449–457
Grodstein F, Stampfer MJ, Colditz GA et al (1997) Postmenopausal hormone therapy and mortality. New Engl J Med 336:1769–1775
Sourander L, Rajala T, Raiha I, Makinen J et al (1998) Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT). Lancet 352:1965–1969 (Erratum appears in Lancet 1999; Jan 23;353(9149):330)
Lando JF, Heck KE, Brett KM (1999) Hormone replacement therapy and breast cancer risk in a nationally representative cohort. Am J Prev Med 17:176–180
Schairer C, Lubin J, Troisi R et al (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283:485–491 (Erratum appears in JAMA 2000; Nov 22–29;284(20):2597)
Manjer J, Malina J, Berglund G et al (2001) Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy. Int J Cancer 92:919–922
Hedblad B, Merlo J, Manjer J et al (2002) Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy. Scand J Public Health 30:12–19
Arzneimittelkommission der Deutschen Ärzteschaft (2003) HRT im Klimakterium. Therapieempfehlungen. Arzneiverordnung in der Praxis. 1. Auflage. http://www.akdae.de/35/10/82_HRT_2003_1Auflage.pdf
Beral V, Million Women, Study Collaborators (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362:419–427 (Erratum appears in Lancet. 2003 Oct 4;362(9390):1160)
Jernstrom H, Bendahl PO, Lidfeldt J et al (2003) A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: The women’s health in the Lund area (WHILA) study (Sweden). Cancer Causes Control 14:673–680
Bakken K, Alsaker E, Eggen AE, Lund E (2004) Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer 112:130–134
Stahlberg C, Pedersen AT, Lynge E et al (2004) Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer 109:721–727
Tjonneland A, Christensen J, Thomsen BL et al (2004) Hormone replacement therapy in relation to breast carcinoma incidence rate ratios: a prospective Danish cohort study. Cancer 100:2328–2337
Ewertz M, Mellemkjaer L, Poulsen AH et al (2005) Hormone use for menopausal symptoms and risk of breast cancer. A Danish cohort study. Br J Cancer 92:1293–1297
Fournier A, Berrino F, Riboli E et al (2005) Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer 114:448–454
Greiser CM, Greiser EM, Dören M (2005) Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials. Hum Reprod Update 11:561–573
Lee SA, Ross RK, Pike MC (2005) An overview of menopausal oestrogen-progestin hormone therapy and breast cancer risk. Br J Cancer 92:2049–2058
Lund E, Bakken K, Dumeaux V et al (2007) Hormone replacement therapy and breast cancer in former users of oral contraceptives—The Norwegian Women and Cancer study. Int J Cancer 121:645–648
Fournier A, Berrino F, Clavel-Chapelon F (2008) Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 107:103–111
Saxena T, Lee E, Henderson D et al (2010) Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study. Cancer Epidemiol Biomarkers Prev 19:2366–2378
Bakken K, Fournier A, Lund E et al (2011) Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into cancer and nutrition. Int J Cancer 128:144–156
Stuenkel CA et al (2015) Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100(11):3975–4011. https://doi.org/10.1210/jc.2015-2236
Prentice RL, Manson JE, Langer RD et al (2009) Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 170:12–23
Manson JE, Chlebowski RT, Stefanick ML et al (2013) Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310(13):1353–1368
Jones ME, Schoemaker MJ, Wright L et al (2016) Menopausal hormone therapy and breast cancer: what ist the true size of the increased risk? Br J Cancer 115(5):607–615. https://doi.org/10.1038/bjc.2016.231
Cordina-Duverger E, Truong T, Anger A et al (2013) Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS ONE 8(11):e78016
Manson JoAnn E, Aragaki AK, Rossouw JE et al (2017) Menopausal hormone therapy and long-term all-cause and cause-specific mortality. The women’s health initiative randomized trials. JAMA 318(10):927–938. https://doi.org/10.1001/jama.2017.11217
Anderson GL, Limacher M, Assaf AR et al (2004) Effects of conjugated equine estrogen in postmenopausal women with a hysterectomy. JAMA 291:1701–1712
Moegele M, Buchholz S, Seitz S, Ortmann O (2012) Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors. Arch Gynecol Obstet 285(5):1397–1402. https://doi.org/10.1007/s00404-011-2181-6
Lethaby A, Suckling J, Barlow D et al (2004) Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2:CD402
Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D (1995) Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 85((2):304–313
Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD (2002) Postmenopausal hormone replacement therapy: scientific review. JAMA 288:872–881
Lacey JV Jr, Brinton LA, Lubin JH et al (2005) Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women. Cancer Epidemiol Biomarkers Prev 14(7):1724–1731
Allen NE, Tsilidis KK, Key TJ et al (2010) Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation into cancer and nutrition. Am J Epidemiol 172:1394–1403
Beral V, Bull D, Reeves G, Million Women Study Collaborators (2005) Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 365(9470):1543–1551
Razavi P, Pike MC, Horn-Ross PL et al (2010) Long-term postmenopausal hormone therapy and endometrial cancer. Cancer Epidemiol Biomarkers Prev 19(2):475–483
Judd H, Mebane-Sims I, Legault C et al (1996) Effects of hormone replacement therapy on Endometrial histology in postmenopausal women. The postmenopausal estrogen/Progestin interventions (PEPI) trial. JAMA 275(5):370–375
Fournier A, Dossus L, Mesrine S et al (2014) Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992–2008. Am J Epidemiol 180(5):508–517
Chlebowski R et al (2015) Aromatase Inhibitors, Tamoxifen, and Endometrial Cancer in Breast Cancer Survivors. Cancer 121:2147–2155
North American Menopause Society (2013) POSITION STATEMENT. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 20(9):888–902. https://doi.org/10.1097/gme.0b013e3182a122c2
North American Menopause Society (2017) POSITION STATEMENT. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 24(7):728–753. https://doi.org/10.1097/GME.0000000000000921
http://www.leitlinienprogramm-onkologie.de/leitlinien/endometriumkarzinom/ Zugegriffen am 31. Juli 2019
Collaborative Group on Epidemiological Studies of Ovarian Cancer (2015) Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet 385:1835–1842
Chan JA, Meyerhardt JA, Chan AT et al (2006) Hormone replacement therapy and survival after colorectal cancer diagnosis. J Clin Oncol 24:5680–5686
Johnson JR, Lacey JV Jr, Lazovich D et al (2009) Menopausal hormone therapy and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev 18:196–203
DeLellis Henderson K, Duan L, Sullivan-Halley J et al (2010) Menopausal hormone therapy use and risk of invasive colon cancer: the california teachers study. Am J Epidemiol 171:415–425
Tsilidis KK, Allen NE, Key TJ et al (2011) Menopausal hormone therapy and risk of colorectal cancer in the European Prospective Investigation into cancer and nutrition. Int J Cancer 128:1881–1889
Newcomb PA, Chia VM, Hampton JM et al (2009) Hormone therapy in relation to survival from large bowel cancer. Cancer Causes Control 20:406–416
Mørch LS, Lidegaard Ø, Keiding N et al (2016) The influence of hormone therapies on colon and rectal cancer. Eur J Epidemiol 31:481–489. https://doi.org/10.1007/s10654-016-0116-z
Simon MS, Chlebowski RT, Wactawski-Wende J et al (2012) Estrogen plus Progestin and Colorectal cancer incidence and mortality. J Clin Oncol 30(32):3983–3990
IARC Monographs (2012) Review of Human Carcinogens (Package of 6 volumes A, B, C, D, E, F) Bd. 100A
Lin KJ, Cheung WY, Lai JY et al (2012) The effect of estrogen vs. combined estrogen-progestin therapy on the risk of colorectal cancer. Int J Cancer 130:419–430
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O. Ortmann, G. Emons und C. Tempfer geben an, dass kein Interessenkonflikt besteht.
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O. Ortmann, Regensburg
Erstveröffentlichung in Gynäkologe (2019): https://doi.org/10.1007/s00129-019-04504-2
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Ortmann, O., Emons, G. & Tempfer, C. S3-Leitlinie: Hormonersatztherapie und Krebsrisiko. Gynäkologische Endokrinologie 18 (Suppl 1), 20–25 (2020). https://doi.org/10.1007/s10304-020-00309-y
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DOI: https://doi.org/10.1007/s10304-020-00309-y