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

Fertil Steril. 2013 Nov;100(5):1405-9. doi: 10.1016/j.fertnstert.2013.07.1983. Epub 2013 Aug 26.

Abstract

Objective: 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.

Design: Experimental study, performed in 2010-2011.

Setting: University hospital.

Patient(s): Eight healthy, normally cycling and parous women volunteered for the study.

Intervention(s): 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.

Result(s): 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.

Conclusion(s): 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.

Keywords: CRH; Metformin; endometrium; urocortin.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Corticotropin-Releasing Hormone / metabolism*
  • Down-Regulation
  • Endometrium / diagnostic imaging
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Female
  • Fertility Agents, Female / administration & dosage
  • Fertility Agents, Female / pharmacology*
  • Greece
  • Healthy Volunteers*
  • Hospitals, University
  • Humans
  • Luteal Phase
  • Metformin / administration & dosage
  • Metformin / pharmacology*
  • Time Factors
  • Ultrasonography
  • Urocortins / metabolism*

Substances

  • Fertility Agents, Female
  • Urocortins
  • Corticotropin-Releasing Hormone
  • Metformin