Abstract
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-1β (IL-1β) 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. Concentrations of prostaglandin F2α (PGF2α) in culture supernatants were measured by enzyme-linked immunosorbent assay.
Results
CMA exerted after IL-1β stimulation a stronger down-regulation 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=.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<.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<.01) on COX-2 mRNA
after IL-1β stimulation.
Conclusion
Among the tested progestins, CMA displayed the most consistent suppression of prostaglandin
biosynthesis in human endometrial explants.
Implication
Among three tested progestins, chlormadinone acetate had the most consistent suppressive
effect on prostaglandins in endometrial explants. These findings support clinical
observations about the efficacy of chlormadinone acetate in dysmenorrhea treatment.
Abbreviations:
CMA (chlormadinone acetate), COX-2 (cyclooxygenase-2), DEX (dexamethasone), DNG (dienogest), DRSP (drospirenone), IL-1β (interleukin-1β), PGE2 (prostaglandin E2), PGF2α (prostaglandin F2α)Keywords
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Article info
Publication history
Published online: August 13, 2018
Accepted:
August 5,
2018
Received in revised form:
July 30,
2018
Received:
March 11,
2018
Footnotes
☆Clinical trial registration number DRKS00009458, Deutsches Register Klinischer Studien.
☆☆This work was supported by Gedeon Richter Plc. (Budapest, Hungary), who produces and sells contraceptives with all three progestins included in the study. To avoid conflicts of interest, the study was conducted as an investigator-initiated trial (IIT). The authors alone are responsible for the content and writing of the paper.
★Complete financial disclosure information for all of the authors
★Dr. Roth reports a personal fee for lectures within the framework of this project.
★Dr. Schäfer reports a grant from Gedeon Richter Plc. (Budapest, Hungary) to carry out the study as IIT; personal fee for a scientific contribution from another manufacturer of contraceptives outside the submitted work.
★Dr. Zahradnik reports a grant from Gedeon Richter Plc. (Budapest, Hungary) to carry out the study as IIT; and a grant from Gruenenthal International (Aachen, Germany) for a preceding IIT study; personal fees from various manufacturers of contraceptives for board membership, consultancy and scientific contributions, outside the submitted work.
★★Funding sources: This work was supported as an investigator-initiated trial by Gedeon Richter Plc. (Budapest, Hungary).
Identification
Copyright
© 2018 Published by Elsevier Inc.
