Effects of different progestins on prostaglandin biosynthesis in human endometrial explants

In: Geburtshilfe und Frauenheilkunde · 2018 · doi:10.1055/s-0038-1671290 · W2898817848
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This study compared the effects of chlormadinone acetate, dienogest, and drospirenone on prostaglandin biosynthesis within a human endometrial explants model.

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This study compared the effects of chlormadinone acetate, dienogest, and drospirenone on prostaglandin biosynthesis using human endometrial explants and YHES cells stimulated with interleukin-1ß. The researchers measured cyclooxygenase-2 mRNA levels and prostaglandin F2α concentrations to assess the inhibitory potential of each progestin. Results indicated that chlormadinone acetate significantly downregulated COX-2 expression and reduced PGF2α release more effectively than the other tested agents, an effect independent of the menstrual cycle phase or the presence of endometriosis. This paper is centrally about endometriosis — specifically evaluating how different progestins affect inflammatory markers in endometrial tissue from patients with and without the condition.

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Abstract

To compare the effects of chlormadinone acetate (CMA), dienogest (DNG) and drospirenone (DRSP) on prostaglandin biosynthesis in a human endometrial explants model.
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Objective

To compare the effects of chlormadinone acetate (CMA), dienogest (DNG) and drospirenone (DRSP) on prostaglandin biosynthesis in a human endometrial explants model. Study Design: Human endometrial explants obtained by aspiration curettage and human endometrial YHES cells were stimulated with interleukin-1ß (IL-1ß) and exposed to CMA, DNG, DRSP or dexamethasone (DEX; YHES cells). Cellular messenger RNA (mRNA) levels of cyclooxygenase-2 (COX-2) were analyzed by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Concentrations of prostaglandin F2α (PGF2α) in culture supernatants were measured by ELISA.

Results

CMA exerted after IL-1ß-stimulation a stronger downregulation of COX-2 mRNA compared to DNG and DRSP in human explants (-55% vs. -40% and 46%, respectively). The effect of CMA on COX-2 mRNA was significantly stronger (p = 0.025) than that of DNG. Moreover, the effect of CMA was independent from cycle phase or presence of endometriosis. In order to evaluate the impact of the investigated progestins on effector molecules, PGF2α release was determined in supernatants. Again, CMA reduced the PGF2α release significantly by an average of -60% (p < 0.01). In contrast, no significant reduction was found for DNG and DRSP. In YHES cells, only DEX but not the progestins under study exerted a significant down-regulating effect (-79%, p < 0.01) on COX-2 mRNA after IL-1ßstimulation.

Conclusion

Among the tested progestins CMA displayed the most consistent suppression of prostaglandin biosynthesis in human endometrial explants.

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