Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.23.10067

Antiproliferative Effect of Metformin on the Endometrium - a Clinical Trial  

Tabrizi, Ali Dastranj (Women's Reproductive Health Research Center, Medicine, Tabriz University of Medical Sciences)
Melli, Manijeh Sayyah (Women's Reproductive Health Research Center, Medicine, Tabriz University of Medical Sciences)
Foroughi, Meraj (Women's Reproductive Health Research Center, Medicine, Tabriz University of Medical Sciences)
Ghojazadeh, Morteza (Women's Reproductive Health Research Center, Medicine, Tabriz University of Medical Sciences)
Bidadi, Sanam (Women's Reproductive Health Research Center, Medicine, Tabriz University of Medical Sciences)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.23, 2015 , pp. 10067-10070 More about this Journal
Abstract
Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.
Keywords
Endometrial hyperplasia; metformin; mestrol; anti-estrogenic influence; endometrial atrophy;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Acmaz G, Aksoy H, Albayrak E, et al (2014). Evaluation of endometrial precancerous lesions in postmenopausal obese women-a high risk group? Asian Pac J Cancer Prev, 15, 195-8.   과학기술학회마을   DOI   ScienceOn
2 Avci CB, Harman E, Dodurga Y, Susluer SY, Gunduz C (2013). Therapeutic potential of an anti-diabetic drug, metformin: alteration of miRNA expression in prostate cancer cells. Asian Pac J Cancer Prev, 14, 765-8.   과학기술학회마을   DOI   ScienceOn
3 Chao A, Lin CY, Tsai CL, et al (2013). Estrogen stimulates the proliferation of human endometrial cancer cells by stabilizing nucleophosmin/B23 (NPM/B23). J Mol Med (Berl), 91, 249-59.   DOI
4 Campagnoli C, Abba C, Ambroggio Set al (2013). Life-style and metformin for the prevention of endometrial pathology in postmenopausal women. Gynecol Endocrinol, 29, 119-24.   DOI   ScienceOn
5 Eftekhar Z, Izadi-Mood N, Yarandi F, et al (2009). Efficacy of megestrol acetate (Megace) in the treatment of patients with early endometrial adenocarcinoma: our experiences with 21 patients. Int J Gynecol Cancer, 19, 249-52.   DOI
6 Fryer LG, Parbu-Patel A, Carling D (2002). The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem, 277, 25226-32.   DOI
7 Huang X, Wellschleger S, Shapiro N, et al (2008). Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J, 412, 211-21.   DOI
8 Hardie DG (2003). The AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology, 144, 5179-83.   DOI
9 Jarboe EA, Mutter GL (2010). Endometrial intraepithelial neoplasia. Semin Diagn Pathol, 27, 215-25.   DOI
10 Ko EM, Walter P, Jackson A, et al (2014). Metformin is associated with improved survival in endometrial cancer. Gynecol Oncol, 132, 438-42   DOI
11 Libby G, Donnelly LA, Donnan PT, et al (2009). New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care, 32, 1620-5   DOI
12 Nevadunsky NS, Van Arsdale A, Strickler HD, et al (2013). Metformin use and endometrial non endometriod cancer survival. Gynecol Oncol, 132, 236-40
13 Mutter GL, Zaino RJ, Baak JP, et al (2007). Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia. Int J Gynecol Pathol, 26, 103-14.   DOI   ScienceOn
14 Mutter GL (2000). Endometrial intraepithelial neoplasia (EIN): Will it bring order to chaos? Gynecol Oncol,76, 287-290.   DOI
15 Mutter GL, Baak JPA, Crum CP, et al (2002). Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol, 190, 462-9.
16 Navaratnarajah R, Pillay OC, Hardiman P (2008). Polycystic ovary syndrome and endometrial cancer. Semin Reprod Med, 26, 62-71.   DOI
17 Prat J, Bentley RC, Russel P, Anderson MC (2009). Endometrial intraepithelial neoplasia. In 'Robboy's Pathology of Female Reproductive Tract', Eds. Elsevier, China, pp 367-397.
18 Perino A, Quartararo P, Catinella E, et al (1987). Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices. Acta Eur Fertil, 18, 137-40.
19 Randall TC, Kurman RJ (1997). Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol, 90, 434-40   DOI
20 Sarfstein R, Friedman Y, Attias-Geva Z, et al (2013). Metformin down regulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. PLoS One, 19, 61537.
21 Tas M, Kutuk MS, Serin IS, et al (2013). Comparison of antiproliferative effects of metformine and progesterone on estrogen-induced endometrial hyperplasia in rats. Gynecol Endocrinol, 29, 311-4.   DOI
22 Shen ZQ, Zhu HT, Lin JF. (2008). Reverse of progestin-resistant atypical endometrial hyperplasia by metformin and oral contraceptives. Obstet Gynecol, 112, 465-7.   DOI
23 Shafiee MN, Khan G, Ariffin R, et al (2013). Preventing endometrial cancer risk in polycystic ovarian syndrome (PCOS) women: Could metformin help? Gynecol Oncol, 13, 1277-8
24 Thigpen JT, Brady MF, Alvarez RD, et al (1999). Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol, 17, 1736-44.
25 van Meurs HS, Bleeker MC, van der Velden J, et al (2013). The incidence of endometrial hyperplasia and cancer in 1031 patients with a granulosa cell tumor of the ovary: long-term follow-up in a population-based cohort study. Int J Gynecol Cancer, 23, 1417-22.   DOI
26 Wheeler DT, Bristow RE, Kurman RJ (2007). Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol, 31, 988-98.   DOI
27 Zhou G, Myers R, Li Y, et al (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest, 108, 1167-74   DOI
28 Zakikhani M, Dowling R, Fantus IG, et al (2006). Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res, 66, 10267-73.