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Rauchen und Östrogene

Smoking and estrogen

  • Leitthema
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Auswirkungen des Rauchens

Rauchen kann die Wirkung exogener und endogener Östrogene reduzieren oder gar ganz aufheben. Dabei werden nicht nur positive Effekte auf klimakterische Beschwerden und auf den Lipidmetabolismus reduziert, auch die Osteoporoseprävention und möglicherweise die Prävention kardiovaskulärer Erkrankungen sind beeinträchtigt. Nachgewiesen werden konnte dies bislang nur für orale Östrogene. Zurückzuführen ist es hauptsächlich auf eine dosisabhängig verstärkte hepatische Clearance, speziell im Zusammenhang mit geringen Östrogenkonzentrationen.

Therapeutische Konsequenzen

Die ausbleibende therapeutische Wirkung sollte bei Raucherinnen nicht durch Zufuhr erhöhter Dosen kompensiert werden, da die Gefahr besteht, dass potenziell mutagene Östrogenmetaboliten entstehen, die das Krebsrisiko erhöhen könnten. Da der günstige Östrogeneffekt bei transdermaler Östrogengabe nicht reduziert wird, sollte diese Anwendungsform bei Raucherinnen bevorzugt werden.

Patientenaufklärung

Frauen, die trotz aller Warnungen das Rauchen nicht einstellen möchten, sollten darüber informiert werden, dass neben den bekannten negativen Wirkungen des Rauchens auch der Erfolg einer Hormontherapie infrage gestellt ist.

Abstract

Impact of smoking

The efficacy of endogenous and exogenous estrogen can be reduced or completely cancelled by smoking. Not only does smoking diminish the beneficial effects of estrogen on climacteric symptoms and the positive effects on lipid metabolism but smoking can also reduce the ability of estrogen to prevent osteoporosis and perhaps also cardiovascular diseases. This is mainly caused by dose-dependent elevated hepatic clearance, partially in conjunction with lower estrogen levels but has so far only been demonstrated with oral estrogen administration.

Therapeutic consequences

The failure of therapeutic efficacy should not be compensated for by increasing the dose in smokers as this might result in the production of potentially mutagenic estrogen metabolites associated with a higher risk of breast cancer. As the favorable effects of estrogens have not been seen to be lost in smokers when applied transdermally, this route should be preferred in smokers.

Patient elucidation

Women who continue to smoke despite all warnings to the contrary should be informed that smoking, in addition to all its other negative effects, can also jeopardize the success of hormone replacement therapy (HRT).

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Literatur

  1. Hartz AJ, He T (2013) Cohort study of risk factors for breast cancer in postmenopausal women. Epidemiol Health 35:e2013003. DOI 10.4178/epih/e2013003

    Article  PubMed Central  PubMed  Google Scholar 

  2. Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the women’s health initiative randomized controlled trial. JAMA 288:312–333

    Google Scholar 

  3. Gao CM, Ding JH, Li SP, Liu YT, Qian Y, Chang J, Tang JH, Tajima K (2013) Active and passive smoking, and alcohol drinking and breast cancer risk in Chinese women. Asian Pac J Cancer Prev 14:993–996

    Article  PubMed  Google Scholar 

  4. Hu FB, Stampfer MJ, Manson JE et al (2000) Trends in the incidence of coronary heart disease and changes in diet and lifestyle in women. N Engl J Med 343:530–537

    Article  CAS  PubMed  Google Scholar 

  5. Gu F, Caporaso NE, Schairer C, Fortner RT, Xu X, Hankinson SE, Eliassen AH, Ziegler RG (2013) Urinary concentrations of estrogens and estrogen metabolites and smoking in caucasian women. Cancer Epidemiol Biomarkers Prev 22:58–68

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Michnovicz JJ, Naganuma H, Hershcopf RJ et al (1988) Increased urinary catechol estrogen excretion in female smokers. Steroids 52:69–83

    Article  CAS  PubMed  Google Scholar 

  7. Zhou B, Yang L, Sun Q, Cong R, Gu H, Tang N, Zhu H, Wang B (2008) Cigarette smoking and the risk of endometrial cancer: a meta-analysis. Am J Med 121:501–508

    Article  CAS  PubMed  Google Scholar 

  8. Olsson H, Bladström A, Ingvar C (2003) Are smoking-associated cancers prevented or postponed in women using hormone replacement therapy? Obstet Gynecol 102:565–570

    Article  CAS  PubMed  Google Scholar 

  9. Ross RK, Pike MC, Vesey MP (1986) Risk factors for uterine fibroids. Br Med J 293:359–362

    Article  CAS  Google Scholar 

  10. Cramer DW, Wilson E, Stillman RJ et al (1986) The relationship of endometriosis to menstrual characteristics, smoking and exercise. JAMA 255:1904–1908

    Article  CAS  PubMed  Google Scholar 

  11. Bjarnason NH, Jorgensen C, Kremmer H, Alexandersen P, Christiansen C (2004) Smoking reduces breast tenderness during oral estrogen-progestogen therapy. Climacteric 7:390–396

    Article  CAS  PubMed  Google Scholar 

  12. Thompson PA, Ambrosone C (2000) Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes in human breast cancer. J Natl Cancer Inst Monogr 27:125–134

    Article  CAS  PubMed  Google Scholar 

  13. Saintot M, Malaveille C, Hautefeuille A, Gerber M (2003) Interactions between genetic polymorphism of cytochrome P450-1B1, sulfotransferase 1A1, catechol-o-methyltransferase and tobacco exposure in breast cancer risk. Int J Cancer 107:652–657

    Article  CAS  PubMed  Google Scholar 

  14. Ishibe N, Hankinson SE, Colditz GA et al (1998) Cigarette smoking, cytochrome P450 1A1 polymorphism, and breast cancer risk in the Nurses’ Health Study. Cancer Res 58:667–671

    CAS  PubMed  Google Scholar 

  15. Cochran CJ, Gallicchio L, Miller SR, Zacur H, Flaws JA (2008) Cigarette smoking, androgen levels, and hot flushes in midlife women. Obstet Gynecol 112:1037–1044

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Bjarnason NH, Byrjalsen I, Jorgensen HL, Christiansen C (2007) The influence of smoking on uterine bleeding during sequential oral hormone therapy. Climacteric 10:147–154

    Article  CAS  PubMed  Google Scholar 

  17. Jensen J, Christiansen C (1988) Effects of smoking on serum lipoproteins and bone mineral content during postmenopausal hormone replacement therapy. Am J Obstet Gynecol 159:820–825

    Article  CAS  PubMed  Google Scholar 

  18. Craig WY, Palomaki GE, Haddow JE (1989) Cigarette smoking and serum lipid and lipoprotein concentration: an analysis of published data. Br Med J 298:784–788

    Article  CAS  Google Scholar 

  19. Baron JA, Farahmand BY, Weiderpass E et al (2001) Cigarette smoking, alcohol consumption, and risk of hip fracture in women. Arch Intern Med 161:983–988

    Article  CAS  PubMed  Google Scholar 

  20. Iqbal J, Sun L, Cao J et al (2013) Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes. Proc Natl Acad Sci U S A 110:11115–11120

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Yoon V, Maalouf NM, Sakhaee K (2012) The effects of smoking on bone metabolism. Osteoporos Int 23:2081–2092

    Article  CAS  PubMed  Google Scholar 

  22. Modena MG, Sismondi P, Mueck AO, Kuttenn F, de Lignieres B, Verhaeghe J, Foidart JM, Caufriez A, Genazzani AR; the TREAT Collaborative Group (2005) New evidence regarding hormone replacement therapies is urgently required. Transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits. Maturitas 52:1–10

    Article  CAS  PubMed  Google Scholar 

  23. Kiel DP, Baron JA, Anderson JJ et al (1992) Smoking eliminates the protective effect of oral estrogen on the risk for hip fracture among women. Ann Int Med 116:716–721

    Article  CAS  PubMed  Google Scholar 

  24. de Valk-de Roo GW, Netelenbos JS, Peters-Muller IR et al (1997) Continuously combined hormone replacement therapy and bone turnover: the influence of dydrogesterone dose, smoking and initial degree of bone turnover. Maturitas 28:153–162

  25. Cubrilo-Turek M, Stavljenic-Rukavina A, Turek S et al (1999) The usefulness of biochemical markers in predicting the response of hormone replacement therapy in perimenopausal smoking healthy women. Coll Antropol 23:195–201

    CAS  PubMed  Google Scholar 

  26. Leino A, Impivaara O, Kaitsaari M (1997) Effects of HRT on bone in women smokers and alcohol consumers. J Bone Miner Res 12:S355

    Google Scholar 

  27. Bjarnason NH, Jorgensen HL, Christiansen C (2012) Acute and long-term estradiol kinetics in smoking postmenopausal women. Climacteric 15:449–454

    Article  CAS  PubMed  Google Scholar 

  28. Mueck AO, Bühling K (2013) Erhöhte kardiovaskuläre Mortalität in der (späteren) Postmenopause. Durch Östrogenmangel bedingt? Gynäkologische Endokrinologie 11:256–263

    Article  CAS  Google Scholar 

  29. Girdler SS, Hinderliter AL, West SG et al (2000) Postmenopausal smokers show reduced hemodynamic benefit from oral hormone replacement. Am J Cardiology 86:590–592

    Article  CAS  Google Scholar 

  30. Ylikorkala O, Cacciatore B, Paakari I et al (1998) The long-term effects of oral and transdermal postmenopausal hormone replacement therapy on nitric oxide, endothelin-1, prostacyclin, and thromboxane. Fertil Steril 69:883–888

    Article  CAS  PubMed  Google Scholar 

  31. Geisler J, Omsjo IH, Helle SI et al (1999) Plasma oestrogen fractions in postmenopausal women receiving hormone replacement therapy: influence of route of administration and cigarette smoking. J Endocrinology 162:265–270

    Article  CAS  Google Scholar 

  32. Khuder SA, Mutgi AB, Nugent S (2001) Smoking and breast cancer: a meta-analysis. Rev Environ Health 16:253–261

    Article  CAS  PubMed  Google Scholar 

  33. Reynolds P (2013) Smoking and breast cancer. J Mammary Gland Biol Neoplasia 18:15–23

    Article  PubMed  Google Scholar 

  34. Glantz SA, Johnson KC (2014) The surgeon general report on smoking and health 50 years later: breast cancer and the cost of increasing caution. Cancer Epidemiol Biomarkers Prev 23:37–46

    Article  PubMed  Google Scholar 

  35. WHI Investigators Writing Group (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. JAMA 289:3243–3253

    Article  Google Scholar 

  36. Mueck AO, Seeger H (2014) Risiko von Brustkrebs unter "hormone replacement therapy". Klinische Daten und experimentell-biologische Plausibilität. Gynäkologische Endokrinologie 12:149–155

  37. Stanczyk FZ (2011) Editorial. Can the increase in breast cancer observed in the estrogen plus progestin arm of the Women’s Health Initiative trial be explained by progesterone receptor membrane component 1? Menopause 18:833–834

  38. Neubauer H, Ma Q, Zhou J, Yu Q, Ruan X, Seeger H, Fehm T, Mueck AO (2013) Possible role of PGRMC1 in breast cancer development. Climacteric 16:509–513

    Article  CAS  PubMed  Google Scholar 

  39. Band PR, Le ND, Fang R, Deschamps M (2002) Carcinogenic and endocrine disrupting effects of cigarette smoke and risk of breast cancer. Lancet 360:1044–1049

    Article  CAS  PubMed  Google Scholar 

  40. Russo J, Russo IH (2011) The role of the basal stem cell of the human breast in normal development and cancer. Adv Exp Med Biol 720:121–34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Service RF (1998) New role for estrogen in cancer? Science 279(5357):1631–1633

  42. Seeger H, Wallwiener D, Krämer E, Mueck AO (2006) Comparison of possible carcinogenic estradiol metabolites: Effects on proliferation, apoptosis and metastasis of human breast cancer cells. Maturitas 54:72–77

    Article  CAS  PubMed  Google Scholar 

  43. Berstein LM, Tsyrlina EV, Kolesnik OS et al (2000) Catecholestrogens excretion in smoking and non-smoking postmenopausal women receiving estrogen replacement therapy. J Steroid Biochem Mol Biol 72:143–147

    Article  CAS  PubMed  Google Scholar 

  44. Michnovicz JJ, Hershcopf RJ, Naganuma H et al (1986) Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking. N Engl J Med 315:1305–1309

    Article  CAS  PubMed  Google Scholar 

  45. Lippert TH, Seeger H, Mueck AO (2001) Pharmacology and toxicology of different estrogens. Gynecol Endocrinol 15(Suppl 4):26–33

    Google Scholar 

  46. Mueck AO, Ruan X (2011) Benefits and risks during HRT – main safety issue breast cancer. Horm Mol Biol Clin Invest 5:105–116

  47. Lippert TH, Seeger H, Mueck AO (2000) The impact of estrogen metabolites on carcinogenesis. Steroids 65:357–369

    Article  CAS  PubMed  Google Scholar 

  48. Polesel J, Serraino D, Zucchetto A, Lucenteforte E, Dal Maso L, Levi F, Negri E, Montella M, Franceschi S, Talamini R, La Veccia C (2009) Cigarette smoking and endometrial cancer risk: the modifying effect of obesity. Eur J Cancer Prev 18:476–481

    Article  CAS  PubMed  Google Scholar 

  49. Mueck AO, Seeger H, Lippert TH (2002) Estradiol metabolism and malignant disease. Review. Maturitas 43:1–10

    Article  CAS  PubMed  Google Scholar 

  50. Mueck AO, Seeger H (2010) 2-Methoxyestradiol - biology and mechanism of action. Steroids 75:625–631

    Article  CAS  PubMed  Google Scholar 

  51. Seeger H, Mueck AO, Lippert TH (1998) Estradiol metabolism during oral and transdermal estradiol replacement therapy in the postmenopause. Horm Metab Res 30:598–601

  52. Seeger H, Mueck AO, Lippert TH (2000) Effect of norethisterone acetate on estrogen metabolism in postmenopausal women. Horm Metab Res 32:436–439

    Article  CAS  PubMed  Google Scholar 

  53. Mueck AO, Seeger H, Gräser T, Lippert TH (2001) Effect of postmenopausal HRT and of oral contraceptives on estradiol metabolism. Horm Metab Res 33:744–747

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Universitäts-Frauenklinik und Forschungsinstitut für Frauengesundheit, Calwerstr. 7, 72076, Tübingen, Deutschland

    A.O. Mueck & H. Seeger

  2. Capital Medical University, Beijing OB/GYN Hospital, Beijing, China

    A.O. Mueck

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  1. A.O. Mueck
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  2. H. Seeger
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Correspondence to A.O. Mueck.

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A.O. Mueck und H. Seeger geben an, dass kein Interessenkonflikt besteht.

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Mueck, A., Seeger, H. Rauchen und Östrogene. Gynäkologische Endokrinologie 13, 156–162 (2015). https://doi.org/10.1007/s10304-015-0015-5

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