Article

Überkreuz-Vergleich der Pharmakokinetik von Estradiol unter der Hormonsubstitution mit Estradiolvalerat oder mikronisiertem Estradiol

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  • Kinderwunschpraxis am Goetheplatz, Frankfurt
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Abstract

Fragestellung: Ziel dieser randomisierten Überkreuz-Studie war der Vergleich zwischen einer sequenziellen 28-tägigen Hormonsubstitution mit mikronisiertem Estradiol und einer zyklischen 21-tägigen Hormonsubstitution mit Estradiolvalerat im Hinblick auf die Pharmakokinetik des Estradiols. - Patienten und Methoden: 50 postmenopausale Frauen erhielten randomisiert entweder eine 28-tägige Therapie (Trisequens®) oder eine 21-tägige Therapie (Sisare®). Nach einem Auswaschzyklus wurden die Frauen jeweils mit dem anderen Präparat behandelt. Das pharmakokinetische Profil der Estradiolkonzentrationen im Serum wurde am Tag 1, 21 und 28 jeweils vor der Einnahme sowie 1, 2, 4, 6, 8 und 10 Stunden nach der Einnahme gemessen und die AUC (Fläche unter der Zeit-Konzentrations-Kurve) berechnet. - Ergebnisse: Die Estradiolkonzentrationen stiegen von einem mittleren Ausgangswert von 10 pg/ml auf 40 pg/ml (Trisequens®) und 30 pg/ml (Sisare®) am Tag 1 sowie auf 80 pg/ml (Trisequens®) und 60 pg/ml (Sisare®) an und fielen auf 40 pg/ml (Trisequens®) und 10 pg/ml (Sisare®) am Tag 28 ab. Die AUC (berechnet aus beiden Behandlungszyklen) war am Tag 1, 21 und 28 unter der Therapie mit Trisequens® jeweils signifikant höher als mit Sisare®. Dieser Unterschied war jedoch am Tag 1 und 21 des ersten Einnahmezyklus nicht signifikant. - Schlussfolgerungen: Unter der Behandlung mit 2 mg mikronisiertem Estradiol sind die Serumkonzentrationen des Estradiols höher als mit 2 mg Estradiolvalerat. Am Tag 28 kommt es unter der Behandlung mit Sisare® zu einem Abfall des Estradiols auf den Ausgangswert, während sie mit Trisequens® im Bereich der Werte bleiben, die am ersten Einnahmetag gemessen werden. Cross-over comparison of the pharmacokinetics of estradiol during hormone replacement therapy with estradiol valerate or micronized estradiol Summary Objective: The aim of this randomized cross-over study was the comparison between a sequential 28-day hormone replacement therapy (HRT) using micronized estradiol and a cyclic 21-day HRT using estradiol valerate with regard to the pharmacokinetics of estradiol. - Material and Methods: Fifty postmenopausal women were randomly assigned to be treated either with Trisequens® for 28 days or with Sisare® for 21 days. After a wash-out cycle, the women were treated for one cycle with the other preparation in a cross-over fashion. The pharmacokinetic profile of the serum concentrations of estradiol was measured on day 1, 21 and 28 each immediately before and 1, 2, 4, 6, 8, and 10 hours after intake of a tablet, and the AUC (area under the curve) was calculated. - Results: The serum concentrations of estradiol increased from a mean of 10 pg/ml up to 40 pg/ml (Trisequens®) and 30 pg/ml (Sisare®) on day 1, and to 80 pg/ml (Trisequens®) and 60 pg/ml (Sisare®) on day 21, and declined to 40 pg/ml (Trisequens®) and 10 pg/ml (Sisare®) on day 28. The AUC as calculated from both treatment cycles, was significantly higher on day 1, 21, and 28 during treatment with Trisequens® than with Sisare®. This difference was, however, not signifcant on day 1 and 21 of the first treatment cycle. - Conclusion: During treatment with 2 mg micronized estradiol the serum concentrations are significantly higher than with 2 mg estradiol valerate. On day 28 of treatment with Sisare®, the estradiol levels decline to baseline values, while using Trisequens® they remain in the range of those measured on day 1.

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