Zusammenfassung
In der abgebrochenen Womens' Health Initiative waren 50 % der 8500 Frauen unter HRT vor oder während der Studie Raucherinnen - demnach ist die Frage äußerst relevant, inwieweit Rauchen den Estradiolstoffwechsel verändern kann. Durch Rauchen kann die Wirksamkeit von oral verabreichten Estrogenen reduziert bis völlig aufgehoben werden, abhängig von Art, Dauer und Intensität des Nikotinkonsums. Dies betrifft die positiven Estrogenwirkungen auf Hitzewallungen, urogenitale Beschwerden sowie den Lipidstoffwechsel, Osteoporoseprävention und möglicherweise auch günstige vaskuläre Effekte. Wichtigste Ursache ist eine dosisabhängige Erhöhung der hepatischen Clearance, häufig in Verbindung mit erniedrigten Estrogenspiegeln. Eine kompensatorische Erhöhung der Dosen für Raucherinnen sollte aber nicht in Betracht gezogen werden, da dies zu der Bildung von toxischen, sogar potenziell mutagenen Estrogenmetaboliten führen könnte - Substanzen, die kürzlich auch mit einem erhöhten Brustkrebsrisiko in Verbindung gebracht wurden. Bei einer transdermalen Applikation bleiben die günstigen Estrogenwirkungen auch bei Raucherinnen erhalten. Dieser Applikationsweg ermöglicht niedrige Dosierungen und vermeidet gleichzeitig die Bildung unphysiologischer Metaboliten, da die Leber primär umgangen wird. Wenn demnach Frauen trotz aller Warnungen weiter rauchen und eine HRT benötigen, wird die transdermale Applikation empfohlen.
Abstract
In the recent discontinued Women's Health Initiative (WHI) 50 % of the 8500 women on HRT had smoked before or continued to smoke during the study - thus the question as to whether smoking may influence estradiol metabolism is of special relevance. Smoking can reduce or completely cancel the efficacy of orally administered estrogens depending on the type, duration and intensity of nicotine consumption. Not only does smoking diminish the beneficial effects of estrogen on hot flashes, urogenital symptoms, lipid metabolism and osteoporosis prevention, but smoking also may influence positive estrogenic effects on the vasculature. Main cause seems to be a dose-dependent elevated hepatic clearance, partially in conjunction with lower estrogen levels. Compensation by increasing the estrogen dose in smokers should be avoided as this might result in the production of toxic, even potentially mutagenic estrogen metabolites - compounds recently associated with a higher risk of breast cancer. The favorable effects of estrogens are not lost in smokers when they are treated transdermally. This route enables low dosage and also avoids the formation of unphysiological metabolites by bypassing the liver. Women who continue to smoke despite all warnings should therefore be treated via the transdermal route.
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PD Dr. med. Dipl.-Chem. Dr. rer. nat. Alfred O. Mueck
Schwerpunkt für Endokrinologie und Menopause · Universitäts-Frauenklinik
Calwerstraße 7
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Email: Endo.Meno@med.uni-tuebingen.de
