title: The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study.
abstract: The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia , Cheras, Kuala Lumpur , Malaysia .
authors.forename: Mohamad Nasir
authors.initials: MN
authors.lastname: Shafiee
authors.forename: Dahlia Abd
authors.initials: DA
authors.lastname: Malik
authors.forename: Ryia Illani Mohd
authors.initials: RI
authors.lastname: Yunos
authors.forename: William
authors.initials: W
authors.lastname: Atiomo
authors.forename: Mohd Hashim
authors.initials: MH
authors.lastname: Omar
authors.forename: Nur Azurah Abdul
authors.initials: NA
authors.lastname: Ghani
authors.forename: Ahmad Zailani
authors.initials: AZ
authors.lastname: Hatta
authors.forename: Claire
authors.initials: C
authors.lastname: Seedhouse
authors.forename: Caroline
authors.initials: C
authors.lastname: Chapman
authors.forename: Norfilza Mohd
authors.initials: NM
authors.lastname: Mokhtar
mesh_terms: D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D015331:Cohort Studies; D056742:Cyclin D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005498:Follicular Phase / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008296:Malaysia / Q000453:epidemiology; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D050177:Overweight / Q000150:complications / Q000517:prevention & control*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: C000595707:BCL2 protein, human; C080336:CCND2 protein, human; D056742:Cyclin D2; D007004:Hypoglycemic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008687:Metformin
keywords: Endometrial cancer; PCOS; genes; metformin