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.
