Metformin reduces the expression of corticotrophin releasing hormone and urocortin in the endometrium of healthy women

Metformin administration in normally cycling women may decrease the production of CRH and UCN in endometrium during the midluteal phase of the menstrual cycle.


Konstantinos Dafopoulos, M.D., Thomas Vrekoussis, M.D., Nektarios Chalvatzas, M.D., Christina I. Messini, M.D., Sophia N. Kalantaridou, M.D., Panagiotis Georgoulias, M.D., Ioannis E. Messinis, M.D., Ph.D., Antonis Makrigiannakis, M.D.

Volume 100, Issue 5, Pages 1405-1409, November 2013



To investigate the effect of metformin administration on the expression of endometrial corticotrophin-releasing hormone (CRH) and urocortin (UCN) in the midluteal phase of the cycle.


Experimental study, performed in 2010–2011.


University hospital.


Eight healthy, normally cycling and parous women volunteered for the study.


All women were investigated in two nonconsecutive cycles (control cycle, untreated and after one cycle break; trial cycle, oral administration of metformin [850 mg × 2]). Endometrial pipelle biopsies were obtained on day LH+7.

Main Outcome Measure(s):

The endometrial biopsies were immunohistochemically assessed for CRH and UCN expression. Evaluation of positivity was performed by applying the immunoreactive score.


Compared with samples from control cycles, CRH and UCN were significantly reduced in endometrial samples obtained during metformin treatment. This down-regulation was significant both in the endometrial cells and in the endometrial stroma.


This is the first study showing that during the midluteal phase of the cycle, metformin may decrease the production of CRH and UCN in the endometrium. Metformin interference to decidualization could happen by CRH/UCN modification.

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