title: Metformin reduces the expression of corticotropin-releasing hormone and urocortin in the endometrium of healthy women.
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.
  
  
  METHODS
  Experimental study, performed in 2010-2011.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Eight healthy, normally cycling and parous women volunteered for the study.
  
  
  METHODS
  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.
  
  
  METHODS
  The endometrial biopsies were immunohistochemically assessed for CRH and UCN expression. Evaluation of positivity was performed by applying the immunoreactive score.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Thessalia Medical School, Larissa, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dafopoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Vrekoussis
authors.forename: Nektarios
authors.initials: N
authors.lastname: Chalvatzas
authors.forename: Christina I
authors.initials: CI
authors.lastname: Messini
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Kalantaridou
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Georgoulias
authors.forename: Ioannis E
authors.initials: IE
authors.lastname: Messinis
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015536:Down-Regulation; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000494:pharmacology*; D006115:Greece; D064368:Healthy Volunteers; D006785:Hospitals, University; D006801:Humans; D008183:Luteal Phase; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014463:Ultrasonography; D054832:Urocortins / Q000378:metabolism*
chemical_list: D005300:Fertility Agents, Female; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D008687:Metformin
keywords: CRH; Metformin; endometrium; urocortin