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Risiko von Brustkrebs unter „hormone replacement therapy“

Klinische Daten und experimentell-biologische Plausibilität

Risk of breast cancer with hormone replacement therapy

Clinical data and experimental biological plausibility

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Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Die Women’s Health Initiative zeigt mit equinen Östrogenen plus Medroxyprogesteronacetat ein erhöhtes, mit Östrogen allein im Vergleich zu Placebo ein erniedrigtes Brustkrebsrisiko. Dies korreliert mit Beobachtungsstudien. Bei langen Behandlungszeiten (in der „Nurses Health Study“ nach 15 Jahren) wurde auch mit Östrogenen allein ein Risiko gesehen. Die Risikosenkung zeigt sich sowohl bei frühem als auch bei späten Beginn mit Östrogenen, und zwar mit equinen Östrogenen wie auch mit Estradiol. Die klinischen Daten sind biologisch plausibel: Östrogene können protektiv z. B. durch Apoptose wirken, aber auch proliferativ, in seltenen Fällen auch über genotoxische Metaboliten, wie bei genetischen Polymorphismen von normalerweise karzinoprotektiven Schlüsselenzymen und bei ungebremstem oxidativem Zellstress. Nach eigener Forschung finden sich bestimmte Zellstrukturen bei Frauen mit Brustkrebs im malignen, aber nicht in deren gesundem Brustgewebe, die in Verbindung mit stromalen Einflüssen stark proliferierende Effekte synthetischer Gestagene, nicht aber von Progesteron vermitteln. Dies entspricht auch Beobachtungsstudien, die im Gegensatz zu den meisten synthetischen Gestagenen keine Risikoerhöhung mit Progesteron oder mit seinem Retroisomer Dydrogesteron bei Kombination mit Estradiol zeigen. Proliferierende Effekte etwa durch Langzeiteinwirkung bestimmter Metaboliten von Progesteron oder Dydrogesteron sind jedoch nicht auszuschließen; sie sind Gegenstand der derzeitigen Forschung, um Frauen mit erhöhtem Risiko zu identifizieren.

Abstract

The Women’s Health Initiative demonstrated an increased risk of breast cancer with conjugated equine estrogens plus medroxyprogesterone acetate but a reduced one with estrogens alone compared to placebo. These data correlate with observational studies, whereby estrogens alone can increase breast cancer risk after long-term treatment (after 15 years in the Nurses Health Study). A risk decrease has been found for early and also late treatment onset with estrogens and with equine estrogens as well as estradiol. The clinical data are also biologically plausible. Estrogens can be protective by e.g. by increasing apoptosis but also proliferative and in rare cases via genotoxic metabolites as in the case of genetic polymorphisms of normally protective key enzymes and uncontrolled oxidative cell stress. According to own research certain cell membrane structures can be found in cancerous tissue but not in benign tissue of women with breast cancer, which in combination with stromal effects can trigger strong proliferative effects in the presence of synthetic progestins but not by progesterone. These results correlate with clinical observational studies demonstrating no increased breast cancer risk with progesterone or its retroisomer dydrogesterone in combination with estradiol in contrast to the most synthetic progestins. However, long-term proliferative effects cannot be excluded at least for certain metabolites of progesterone and dydrogesterone and are the subject of current research to identify women with increased risk.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. A.O. Mueck und H. Seeger geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren im Sinne einer Originalpublikation.

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Mueck, A., Seeger, H. Risiko von Brustkrebs unter „hormone replacement therapy“. Gynäkologische Endokrinologie 12, 149–155 (2014). https://doi.org/10.1007/s10304-013-0627-6

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