The clinical application of glucagon-like peptide-1 receptor agonists in polycystic ovary syndrome_West China Medical Journal

Authors：

ZHANG Xinxia ¹ ,  TONG Nanwei ²

1. School of Clinical Medicine, Chengdu University of T.C.M, Chengdu, Sichuan 610075, P. R. China;
2. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

TONG Nanwei, Email: tongnw@scu.edu.cn

Keywords：

Polycystic ovary syndrome; Glucagon-like peptide-1 receptor agonists; Clinical trial

DOI：

10.7507/1002-0179.201803194

Video：

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Polycystic ovary syndrome (PCOS) affects many women of reproductive age, including ovarian and metabolic dysfunction. Major therapeutic goals include weight loss and improved insulin resistance. The effects of weight loss and increased insulin sensitivity of glucagon-like peptide-1 (GLP-1) receptor agonists provide another opportunity and pathway for the treatment of PCOS patients, especially those with metabolic abnormalities. This paper reviews the metabolism and reproductive outcomes about GLP-1 receptor agonists for PCOS by searching for literatures of clinical trials from PubMed in the past 10 years, in oder to provide new ideas and clinical evidence for clinical treatment of PCOS.

Citation： ZHANG Xinxia, TONG Nanwei. The clinical application of glucagon-like peptide-1 receptor agonists in polycystic ovary syndrome. West China Medical Journal, 2018, 33(5): 611-615. doi: 10.7507/1002-0179.201803194 Copy

1.	Rocca ML, Venturella R, Mocciaro R, et al. Polycystic ovary syndrome: chemical pharmacotherapy. Expert Opin Pharmacother, 2015, 16(9): 1369-1393.
2.	Stracquadanio M, Ciotta L. Metabolic aspects of PCOS-treatment with insulin sensitizers. Switzerland: Springer International Publishing, 2015: 3-62.
3.	Randeva HS, Tan BK, Weickert MO, et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev, 2012, 33(5): 812-841.
4.	Jarrett BY, Lujan ME. Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS. Reproduction, 2016, 153(1): REP-16-0385.
5.	Hirschberg AL. Polycystic ovary syndrome, obesity and reproductive implications. Womens Health (Lond Engl), 2009, 5(5): 529-540; quiz 541-542.
6.	Moran LJ, Hutchison SK, Norman RJ, et al. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev, 2011 (7): CD007506.
7.	Haqq L, Mcfarlane J, Dieberg G, et al. Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr Connect, 2014, 3(1): 36-46.
8.	Thomson RL, Buckley JD, Noakes M, et al. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab, 2008, 93(9): 3373-3380.
9.	Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril, 2008, 89(3): 505-522.
10.	Ayyad C, Andersen T. Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes Rev, 2000, 1(2): 113-119.
11.	中華醫學會婦產科學分會內分泌學組及指南專家組. 多囊卵巢綜合征中國診療指南. 中華婦產科雜志, 2018, 53(1): 2-6.
12.	中國醫師協會內分泌代謝科醫師分會. 多囊卵巢綜合征診治內分泌專家共識. 中華內分泌代謝雜志, 2018, 34(1): 1-7.
13.	Vrbikova J, Hill M, Bendlova B, et al. Incretin levels in polycystic ovary syndrome. Eur J Endocrinol, 2008, 159(2): 121-127.
14.	Conway G, Dewailly D, Diamanti-Kandarakis E, et al. On behalf of the ESE PCOS special interest group. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol, 2014, 171(4): 1-29.
15.	Elkind-Hirsch K, Marrioneaux O, Bhushan M, et al. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab, 2008, 93(7): 2670-2678.
16.	Craig C, Lerner K, Lamendola C, et al. Effect of exenatide on menstrual cyclicity, weight, and metabolic profile in insulin resistant women with PCOS. Diabetes, 2014, 63: A248.
17.	Liu X, Zhang Y, Zheng SY, et al. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome. Clin Endocrinol (Oxf), 2017, 87(6): 767-774.
18.	Yang Q, Wang F. Successful pregnancy after improving insulin resistance with the glucagon-like peptide-1 analogue in a woman with polycystic ovary syndrome: a case report and review of the literature. Gynecol Obstet Invest, 2016, 81(5): 477-480.
19.	Fr?ssing S, Nylander M, Chabanova E, et al. Effect of liraglutide on ectopic fat in polycystic ovary syndrome: a randomized clinical trial. Diabetes Obes Metab, 2018, 20(1): 215-218.
20.	Fr?ssing S, Nylander M, Kistorp C, et al. Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS. Endocr Connect, 2018, 7(1): 115-123.
21.	Nylander M, Fr?ssing S, Clausen HV, et al. Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. Reprod Biomed Online, 2017, 35(1): 121-127.
22.	Jensterle M, Salamun V, Kocjan T, et al. Short term monotherapy with GLP-1 receptor agonist liraglutide or PDE 4 inhibitor roflumilast is superior to metformin in weight loss in obese PCOS women: a pilot randomized study. J Ovarian Res, 2015, 8: 32.
23.	Jensterle M, Kravos NA, Pfeifer M, et al. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome. Hormones (Athens), 2015, 14(1): 81-90.
24.	Jensterle M, Kocjan T, Kravos NA, et al. Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome. Endocr Res, 2015, 40(3): 133-138.
25.	Jensterle Sever M, Kocjan T, Pfeifer M, et al. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol, 2014, 170(3): 451-459.
26.	Jensterle M, Goricar K, Janez A. Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study. Exp Ther Med, 2016, 11(4): 1194-1200.
27.	Jensterle M, Kravos NA, Gori?ar K, et al. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. BMC Endocr Disord, 2017, 17(1): 5.
28.	Kahal H, Aburima A, Ungvari T, et al. The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls. BMC Endocr Disord, 2015, 15: 14.
29.	Kahal H, Abouda G, Rigby AS, et al. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf), 2014, 81(4): 523-528.
30.	Rasmussen CB, Lindenberg S. The effect of liraglutide on weight loss in women with polycystic ovary syndrome: an observational study. Front Endocrinol (Lausanne), 2014, 5: 140.
31.	Jensterle M, Pir? B, Gori?ar K, et al. Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study. Eur J Clin Pharmacol, 2015, 71(7): 817-824.

1. Rocca ML, Venturella R, Mocciaro R, et al. Polycystic ovary syndrome: chemical pharmacotherapy. Expert Opin Pharmacother, 2015, 16(9): 1369-1393.
2. Stracquadanio M, Ciotta L. Metabolic aspects of PCOS-treatment with insulin sensitizers. Switzerland: Springer International Publishing, 2015: 3-62.
3. Randeva HS, Tan BK, Weickert MO, et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev, 2012, 33(5): 812-841.
4. Jarrett BY, Lujan ME. Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS. Reproduction, 2016, 153(1): REP-16-0385.
5. Hirschberg AL. Polycystic ovary syndrome, obesity and reproductive implications. Womens Health (Lond Engl), 2009, 5(5): 529-540; quiz 541-542.
6. Moran LJ, Hutchison SK, Norman RJ, et al. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev, 2011 (7): CD007506.
7. Haqq L, Mcfarlane J, Dieberg G, et al. Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr Connect, 2014, 3(1): 36-46.
8. Thomson RL, Buckley JD, Noakes M, et al. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab, 2008, 93(9): 3373-3380.
9. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril, 2008, 89(3): 505-522.
10. Ayyad C, Andersen T. Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes Rev, 2000, 1(2): 113-119.
11. 中華醫學會婦產科學分會內分泌學組及指南專家組. 多囊卵巢綜合征中國診療指南. 中華婦產科雜志, 2018, 53(1): 2-6.
12. 中國醫師協會內分泌代謝科醫師分會. 多囊卵巢綜合征診治內分泌專家共識. 中華內分泌代謝雜志, 2018, 34(1): 1-7.
13. Vrbikova J, Hill M, Bendlova B, et al. Incretin levels in polycystic ovary syndrome. Eur J Endocrinol, 2008, 159(2): 121-127.
14. Conway G, Dewailly D, Diamanti-Kandarakis E, et al. On behalf of the ESE PCOS special interest group. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol, 2014, 171(4): 1-29.
15. Elkind-Hirsch K, Marrioneaux O, Bhushan M, et al. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab, 2008, 93(7): 2670-2678.
16. Craig C, Lerner K, Lamendola C, et al. Effect of exenatide on menstrual cyclicity, weight, and metabolic profile in insulin resistant women with PCOS. Diabetes, 2014, 63: A248.
17. Liu X, Zhang Y, Zheng SY, et al. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome. Clin Endocrinol (Oxf), 2017, 87(6): 767-774.
18. Yang Q, Wang F. Successful pregnancy after improving insulin resistance with the glucagon-like peptide-1 analogue in a woman with polycystic ovary syndrome: a case report and review of the literature. Gynecol Obstet Invest, 2016, 81(5): 477-480.
19. Fr?ssing S, Nylander M, Chabanova E, et al. Effect of liraglutide on ectopic fat in polycystic ovary syndrome: a randomized clinical trial. Diabetes Obes Metab, 2018, 20(1): 215-218.
20. Fr?ssing S, Nylander M, Kistorp C, et al. Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS. Endocr Connect, 2018, 7(1): 115-123.
21. Nylander M, Fr?ssing S, Clausen HV, et al. Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: a randomized clinical trial. Reprod Biomed Online, 2017, 35(1): 121-127.
22. Jensterle M, Salamun V, Kocjan T, et al. Short term monotherapy with GLP-1 receptor agonist liraglutide or PDE 4 inhibitor roflumilast is superior to metformin in weight loss in obese PCOS women: a pilot randomized study. J Ovarian Res, 2015, 8: 32.
23. Jensterle M, Kravos NA, Pfeifer M, et al. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome. Hormones (Athens), 2015, 14(1): 81-90.
24. Jensterle M, Kocjan T, Kravos NA, et al. Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome. Endocr Res, 2015, 40(3): 133-138.
25. Jensterle Sever M, Kocjan T, Pfeifer M, et al. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol, 2014, 170(3): 451-459.
26. Jensterle M, Goricar K, Janez A. Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study. Exp Ther Med, 2016, 11(4): 1194-1200.
27. Jensterle M, Kravos NA, Gori?ar K, et al. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. BMC Endocr Disord, 2017, 17(1): 5.
28. Kahal H, Aburima A, Ungvari T, et al. The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls. BMC Endocr Disord, 2015, 15: 14.
29. Kahal H, Abouda G, Rigby AS, et al. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf), 2014, 81(4): 523-528.
30. Rasmussen CB, Lindenberg S. The effect of liraglutide on weight loss in women with polycystic ovary syndrome: an observational study. Front Endocrinol (Lausanne), 2014, 5: 140.
31. Jensterle M, Pir? B, Gori?ar K, et al. Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study. Eur J Clin Pharmacol, 2015, 71(7): 817-824.

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