Maintaining women’s reproductive health in the context of drug-induced obesity correction (tirzepatide)

Overweight and obesity are diseases of the 21st century, in which quantitative and qualitative changes in adipose tissue contribute to adverse metabolic, somatic, and psychosocial consequences. The impact of obesity on reproductive health is multifaceted and ranges from fertility problems to the development of hyperplastic and neoplastic processes in the reproductive organs. However, with the advent of a new class of pharmacological agents (glucagon-like peptide-1 receptor agonists, GLP-1RAs), significant weight loss can be achieved, optimal reproductive function can be maintained, and associated cancer and cardiometabolic risks can be reduced. Experts believe their use should be considered during preliminary consultation. Currently, tirzepatide, which has competitive advantages over GLP-1RAs, has been developed for effective weight loss. It is a dual agonist of the GLP-1 receptor and a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor. Tirzepatide reduces body weight by increasing insulin secretion and tissue sensitivity, reducing glucagon secretion, delaying gastric emptying, promoting lipogenesis, and influencing eating behavior. Before the advent of GLP-1 agonists and tirzepatide, bariatric surgery was considered the most effective weight loss method, capable of achieving significant weight loss. Given the inherent risks of surgery and the potential for vitamin and mineral deficiencies, bariatric surgery should not be considered a first-line treatment for obesity. This article will present the key benefits of tirzepatide, which can be effectively used to treat obesity in women with various reproductive health conditions.

1. Jaacks LM, Vandevijvere S. The obesity transition: stages of the global epidemic. Lancet Diabetes Endocrinol. 2019;7(3):231–240. https://doi.org/10.1016/s2213-8587(19)30026-9.

2. Iacobini C, Pugliese G, Blasetti Fantauzzi C, Federici M, Menini S. Metabolically healthy versus metabolically unhealthy obesity. Metabolism. 2019;92:51–60. https://doi.org/10.1016/j.metabol.2018.11.009.

3. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403(10431):1027–1050. https://doi.org/10.1016/S0140-6736(23)02750-2.

4. Acosta A, Camilleri M, Abu Dayyeh B, Calderon G, Gonzalez D, McRae A et al. Selection of Antiobesity Medications Based on Phenotypes Enhances Weight Loss: A Pragmatic Trial in an Obesity Clinic. Obesity. 2021;29(4):662–671. https://doi.org/10.1002/oby.23120.

5. Schon SB, Cabre HE, Redman LM. The impact of obesity on reproductive health and metabolism in reproductive-age females. Fertil Steril. 2024;122(2):194–203. https://doi.org/10.1016/j.fertnstert.2024.04.036.

6. Duah J, Seifer DB. Medical therapy to treat obesity and optimize fertility in women of reproductive age: a narrative review. Reprod Biol Endocrinol. 2025;23(1):2. https://doi.org/10.1186/s12958-024-01339-y.

7. Ludwig DS, Apovian CM, Aronne LJ, Astrup A, Cantley LC, Ebbeling CB et al. Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models. Eur J Clin Nutr. 2022;76:1209–1221. https://doi.org/10.1038/s41430-022-01179-2.

8. Garcia-Garcia RM. Integrative control of energy balance and reproduction in females. ISRN Vet Sci. 2012;2012:121389. https://doi.org/10.5402/2012/121389.

9. Pico C, Palou M, Pomar CA, Rodriguez AM, Palou A. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord. 2022;23:13–30. https://doi.org/10.1007/s11154-021-09687-5.

10. Alhabeeb H, AlFaiz A, Kutbi E, AlShahrani D, Alsuhail A, AlRajhi S et al. Gut hormones in health and obesity: the upcoming role of short chain fatty acids. Nutrients. 2021;13:481. https://doi.org/10.3390/nu13020481.

11. Yu X, Chen S, Funcke JB, Straub LG, Pirro V, Emont MP et al. The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice. Cell Metab. 2025;37(1):187–204.e7. https://doi.org/10.1016/j.cmet.2024.11.003.

12. Giviziez CR, Sanchez EG, Approbato MS, Maia MC, Fleury EA, Sasaki RS. Obesity and anovulatory infertility: A review. JBRA Assist Reprod. 2016;20(4):240–245. https://doi.org/10.5935/1518-0557.20160046.

13. Kuchenbecker WK, Groen H, Zijlstra TM, Bolster JH, Slart RH, van der Jagt EJ et al. The subcutaneous abdominal fat and not the intraabdominal fat compartment is associated with anovulation in women with obesity and infertility. J Clin Endocrinol Metab. 2010;95(5):2107–2112. https://doi.org/10.1210/jc.2009-1915.

14. Joham A, Norman R, Stener-Victorin E, Legro R, Franks S, Moran L et al. Polycystic ovary syndrome. Lancet Diabetes Endocrinol. 2022;10:668–680. https://doi.org/10.1016/S2213-8587(22)00163-2.

15. Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, Casson P et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119–129. https://doi.org/10.1056/NEJMoa1313517.

16. Reynolds KA, Boudoures AL, Chi MM, Wang Q, Moley KH. Adverse effects of obesity and/or high-fat diet on oocyte quality and metabolism are not reversible with resumption of regular diet in mice. Reprod Fertil Dev. 2015;27(4):716–724. https://doi.org/10.1071/RD14251.

17. Leary C, Leese HJ, Sturmey RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum Reprod. 2015;30(1):122–132. https://doi.org/10.1093/humrep/deu276.

18. Merhi Z, Buyuk E, Berger D, Zapantis A, Israel D, Chua S Jr et al. Leptin suppresses anti-mullerian hormone gene expression through the JAK2/STAT3 pathway in luteinized granulosa cells of women undergoing IVF. Hum Reprod. 2013;28(6):1661–1669. https://doi.org/10.1093/humrep/det072.

19. Bernardi LA, Carnethon MR, de Chavez PJ, Ikhena DE, Neff LM, Baird DD et al. Relationship between obesity and anti-mullerian hormone in reproductive-aged African American women. Obesity. 2017;25(1):229–235. https://doi.org/10.1002/oby.21681.

20. Jaswa EG, Rios JS, Cedars MI, Santoro NF, Pavone MEG, Legro RS et al. Increased body mass index is associated with a nondilutional reduction in antimullerian hormone. J Clin Endocrinol Metab. 2020;105:3234–242. https://doi.org/10.1210/clinem/dgaa436.

21. Fabozzi G, Cimadomo D, Maggiulli R, Vaiarelli A, Badajoz V, Aura M et al. Association between oocyte donors’ or recipients’ body mass index and clinical outcomes after first single blastocyst transfers – the uterus is the most affected. Fertil Steril. 2024;121(2):281–290. https://doi.org/10.1016/j.fertnstert.2023.07.029.

22. Peterson A, Wu H, Kappy M, Kucherov A, Singh M, Lieman H et al. Higher live birth rates are associated with a normal body mass index in preimplantation genetic testing for aneuploidy frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study. Fertil Steril. 2024;121(2):291–298. https://doi.org/10.1016/j.fertnstert.2023.11.005.

23. Rhee JS, Saben JL, Mayer AL, Schulte MB, Asghar Z, Stephens C et al. Dietinduced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy. Hum Reprod. 2016;31(6):1315–1326. https://doi.org/10.1093/humrep/dew048.

24. Bellver J, Marin C, Lathi RB, Murugappan G, Labarta E, Vidal C et al. Obesity affects endometrial receptivity by displacing the window of implantation. Reprod Sci. 2021;28(11):3171–3180. https://doi.org/10.1007/s43032-021-00631-1.

25. Giuliani E, Schon S, Yang K, Burns G, Neff L, Remmer H et al. Obesityinduced follicular phase endometrial proteome dysregulation in a wellphenotyped population. F S Sci. 2022;3(4):367–375. https://doi.org/10.1016/j.xfss.2022.06.002.

26. Dos Santos E, Serazin V, Morvan C, Torre A, Wainer R, de Mazancourt P, Dieudonné MN. Adiponectin and leptin systems in human endometrium during window of implantation. Fertil Steril. 2012;97(3):771–778.E1. https://doi.org/10.1016/j.fertnstert.2011.12.042.

27. Arnold M, Leitzmann M, Freisling H, Bray F, Romieu I, Renehan A, Soerjomataram I. Obesity and cancer: An update of the global impact. Cancer Epidemiol. 2016;41:8–15. https://doi.org/10.1016/j.canep.2016.01.003.

28. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K. Body Fatness and Cancer – Viewpoint of the IARC Working Group. N Engl J Med. 2016;375(8):794–798. https://doi.org/10.1056/NEJMsr1606602.

29. Osadchuk MA, Vasilieva IN, Kozlov VV, Mitrokhina OI. Metabolic syndrome as a risk factor for oncogenesis. Profilakticheskaya Meditsina. 2023;26(1):70–79. (In Russ.) https://doi.org/10.17116/profmed20232601170.

30. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–578. https://doi.org/10.1016/S0140-6736(08)60269-X.

31. Kokts-Porietis RL, Elmrayed S, Brenner DR, Friedenreich CM. Obesity and mortality among endometrial cancer survivors: A systematic review and metaanalysis. Obes Rev. 2021;22(12):e13337. https://doi.org/10.1111/obr.13337.

32. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013;31(20):2607–2618. https://doi.org/10.1200/JCO.2012.48.2596.

33. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and body size: individual participant meta-analysis including 25,157 women with ovarian cancer from 47 epidemiological studies. PLoS Med. 2012;9:e1001200–e1001200. https://doi.org/10.1371/journal.pmed.1001200.

34. Pérez-Martín AR, Castro-Eguiluz D, Cetina-Pérez L, Velasco-Torres Y, Bahena-González A, Montes-Servín E et al. Impact of metabolic syndrome on the risk of endometrial cancer and the role of lifestyle in prevention. Bosn J Basic Med Sci. 2022;22(4):499–510. https://doi.org/10.17305/bjbms.2021.6963.

35. Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists. J Clin Endocrinol Metab. 2020;105(8):e2695–709. https://doi.org/10.1210/clinem/dgaa285.

36. Kalra S, Bhattacharya S, Kapoor N. Contemporary Classification of Glucagon-Like Peptide 1 Receptor Agonists (GLP1RAs). Diabetes Ther. 2021;12(8):2133–2147. https://doi.org/10.1007/s13300-021-01113-y.

37. Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE. The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Hum Reprod Update. 2019;25(4):504–517. https://doi.org/10.1093/humupd/dmz019.

38. Vergès B. Do antiobesity medical treatments have a direct effect on adipose tissue? Ann Endocrinol. 2024;85(3):179–183. https://doi.org/10.1016/j.ando.2024.05.021.

39. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131–2157. https://doi.org/10.1053/j.gastro.2007.03.054.

40. Cherkashin DV, Salukhov VV, Khalimov YS. Cardiovascular effects of semaglutide and tirzepatide and their potential for cardioprevention. Meditsinskiy Sovet. 2025;19(13):157–172. (In Russ.) https://doi.org/10.21518/ms2025-323.

41. Yakushevskaya OV. The effects of hormone replacement therapy: а window of opportunity for the cardiovascular system. Meditsinskiy Sovet. 2023;(5):148–154. (In Russ.) https://doi.org/10.21518/ms2023-072.

42. Sattar N, McGuire DK, Pavo I, Weerakkody GJ. Tirzepatide cardiovascular event risk assessment: A pre-specified meta-analysis. Nat Med. 2022;28(3):591–598. https://doi.org/10.1038/s41591-022-01707-4.

43. Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26–36. https://doi.org/10.1056/NEJMoa2416394.

44. Melson E, Miras AD, Papamargaritis D. Future therapies for obesity. Clin Med. 2023;23(4):337–346. https://doi.org/10.7861/clinmed.2023-0144.

45. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–2786. https://doi.org/10.2337/dci22-0034.

46. Lugovik IA, Babina AV, Arutyunyan SS, Ermolaeva DО, Saparova VB, Kobeleva TN et al. The first generic tirzepatide GP30931: physicochemical and biological similarity to the reference drug. Drug Development and Registration. 2025;14(2):54–74. (In Russ.) https://doi.org/10.33380/2305-2066-2025-14-2-2084.