Sind Estrogene Karzinogene?

Zusammenfassung

Es ist allgemein akzeptiert, dass eine reine Estrogensubstitution oder sonstige hyperestrogene Zustände die Entstehung von Endometriumkarzinomen begünstigen. Ein Zusammenhang zwischen Estrogenexposition und dem Auftreten von Mammakarzinomen ist nicht mehr von der Hand zu weisen. Auch eine Assoziation zwischen langjähriger Estrogensubstitution und dem Risiko, an einem Ovarialkarzinom zu erkranken, wird postuliert. Bisher wurden Estrogene als typische Tumorpromotoren angesehen, die durch ihre rezeptorvermittelte mitogene Wirkung die statistische Wahrscheinlichkeit für das Auftreten von spontanen Mutationen erhöhen. Neuere experimentelle Befunde zeigen, dass Metabolite der Estrogene, insbesondere die 4-Hydroxyestrogene über weitere Stoffwechselprodukte direkt die DNA schädigen und transformierende Mutationen induzieren können. Die klinische Relevanz dieser mutagenen Eigenschaften der Estrogene ist noch nicht belegt, könnte aber große Bedeutung gewinnen. Erste molekular-epidemiologische Studien lassen vermuten, dass es Frauen geben könnte, deren Estrogenmetabolismus vermehrt mutagene Metaboliten erzeugt und die durch exogene, eventuell sogar durch endogene Estrogene einem höheren Mamma-, Endometrium- oder Ovarialkarzinomrisiko unterliegen. Hieraus lassen sich möglicherweise neue präventive Strategien entwickeln. Zur Zeit rechtfertigt die Datenlage nicht einen Verzicht auf eine indizierte Hormontherapie mit Estrogenen bzw. Estrogenen und Gestagenen (bei Frauen mit Uterus). Es ist jedoch ratsam, eine solche Hormontherapie nur bei klarer Indikation einzusetzen und diese, dem aktuellen Trend folgend, zeitlich zu begrenzen.

Abstract

It is well accepted that unopposed estrogens increase the risk of developing endometrial cancer. A relationship between estrogen exposure and the risk for breast cancer is very probable. In addition, an association of long-term estrogen substitution and ovarian cancer risk has been postulated recently. Estrogens have been considered as typical tumor promotors. Due to their estrogen-receptor-mediated mitogenic activity, these steroids were supposed to increase the statistical probability of spontaneous mutations. Recent experimental findings, however, suggest that estrogen metabolites, in particular 4-hydroxyestrogens are capable of inducing DNA-damage and transforming mutations. The clinical relevance of these genotoxic properties of estrogens remains to be established, but could obtain great importance. First molecular-epidemiologic studies suggest that due to the specific activity of their estrogen metabolizing enzymes some women might produce relevant amounts of mutagenic estrogen metabolites, increasing their risk for breast-, endometrial- or ovarian cancer respectively. These findings might result in novel preventive strategies. The present data do not justify to abandon the practice of hormone replacement therapy with estrogens or estrogens plus progestins in non hysterectomised women. It seems to be wise, however, to restrict hormone replacement therapy to symptomatic women with a clear indication and, according to the actual trend, limit it temporarily.

Schlüsselwörter

Estrogene - Catecholestrogene - 4-Hydroxyestrogene - Karzinogenese

Key words

Estrogens - catecholestrogens - 4-Hydroxyestrogens - carcinogenesis

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