Wissenschaftliche Stellungnahme: Norethisteronacetat (NETA) - eine Risikosubstanz?

Zusammenfassung

Das Mammakarzinom ist ein Dauerthema bei den Diskussionen über die Auswirkungen natürlicher und synthetischer Sexualsteroide. Zahlreiche Theorien und Hypothesen über die Ätiologie sind aufgestellt und verworfen worden. In den letzten Jahren hat die Diskussion an Intensität gewonnen. Basierend auf In-vitro-Untersuchungen mit Mammakarzinom-Zelllinien, bei denen ein kontinuierlicher Gestageneinfluss die Proliferation hemmte, wurde die These aufgestellt, dass die kontinuierlich-kombinierte Hormonsubstitution vor Brustkrebs schütze [[1], [2]]. Nachdem sich herausstellte, dass die Epidemiologie diese Hypothese nicht stützen kann, ist davon kaum noch die Rede. Neuerdings wird auf der Grundlage von In-vitro-Ergebnissen gefordert, dass das Gestagen zyklisch gegeben werden solle, da nur ein Gestagenabfall den Apoptosevorgang auslösen könne [[3]]. Dafür gibt es ebenso wenig eine epidemiologische Basis. Inzwischen gibt es gezielte Versuche, Nortestosteronderivate als brustkrebsfördernd oder in dieser Hinsicht als zumindest problematisch darzustellen. Eine Gruppe von Autoren versucht seit längerer Zeit nachzuweisen, dass die Anwendung von NETA und anderen Nortestosteron-Derivaten wie Levonorgestrel (LNG) bei der oralen Kontrazeption und der Hormonsubstitution das Risiko des Mammakarzinoms erhöht. Dazu wurden selektiv in die Argumentation passende In-vitro-Ergebnisse, klinische Beobachtungen und epidemiologische Befunde zusammengestellt, um eine „Indizienkette“ zum Nachweis dieser Hypothese aufzubauen. Abschließend wird die Verwendung bestimmter Progesteronderivate wie Medrogeston oder Dydrogesteron empfohlen [[4], [5]]. Diese seit Monaten in verschiedenen Zeitschriften immer wieder publizierten Darstellungen werden von einem Pharmahersteller unterstützt, dessen Präparate einen anderen Gestagentyp, nämlich die Progesteronderivate Medrogeston oder Dydrogesteron enthält. Für diese Präparate gibt es weder ausreichende Informationen über die pharmakologischen Eigenschaften (beispielsweise fehlen Angaben über die Rezeptorbindungsaffinitäten) noch epidemiologische Ergebnisse, die einen Hinweis auf das Risiko des Mammakarzinoms, der Atherosklerose oder der venösen Thromboembolien geben könnten.

Summary

For many years, breast cancer has been a main issue in the discussions concerning the effects of natural and synthetic steroids. Numerous theories and hypotheses on the etiology of breast cancer have been advanced and rejected. During the last years the discussion has gained intensity. Based on in vitro-investigations with breast cancer cell lines which revealed an inhibitory effect of progestogens on proliferation when continuously present, it was assumed that continuous combined hormone replacement therapy (HRT) protects against breast cancer [[1], [2]]. The available epidemiological data, however, failed to confirm this thesis. Subsequently, cyclic treatment has been claimed to be the optimal regimen, as in vitro-results suggested that apoptosis is included only by a decline of the progestogen [[3]]. There is, however, also no epidemiological basis for this hypothesis. Recently, it was argued that nortestosterone derivatives may promote the development of breast cancer or may at least be a risky compound in this regard. Several publications in German and international scientific and pseudo-scientific journals tried to prove that the use of norethisterone acetate (NETA) and other nortestosterone derivatives like levonorgestrel for oral contraception and HRT is associated with a higher breast cancer risk. This was attempted by means of a selective compilation of suitable in vitro-results, clinical observations and epidemiological data, in order to construct “circumstantial evidence” for this hypothesis. Subsequently, the use of certain progesterone derivatives like medrogestone or dydrogesterone was recommended [[4], [5]]. It is remarkable that information on the pharmacological properties of the latter progestogens, e.g. binding affinities to the various steroid receptors, is scarce, and epidemiological data on the risk of breast cancer, atherosclerosis or venous thromboembolic diseases during the use of preparations containing estrogens and medrogestone or dydrogesterone, are lacking.

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