Effects of different progestins on prostaglandin biosynthesis in human endometrial explants

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 F_2α (PGF_2α) 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, PGF_2α release was determined in supernatants. Again, CMA reduced the PGF_2α 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.