An exploration of gut hormone therapy to treat infertility caused by Type 2 Diabetes

Alison  Belle Martin; Eileen Duggan

doi:10.33178/SMJ.2024.1.1

Authors

Alison Belle Martin
Eileen Duggan

DOI:

https://doi.org/10.33178/SMJ.2024.1.1

Keywords:

Fertility, Type II Diabetes, Family Medicine

Abstract

Background

Type II Diabetes Mellitus is a common disease associated with multiple debilitating symptoms, including reduced fertility in women of reproductive age. Gut hormone therapies have shown promise in improving fertility in these patients.

Objectives:

To identify the relationship between the human gut microbiota and the successful functioning of the female reproductive system.
To explore treatments to improve bacteria culture in the gut, and to examine if these improvements affect fertility in female patients with Type II Diabetes.

Method:

A systematic search was undertaken; studies were collected from PubMed and The Diabetology and Metabolic Syndrome Journal. Searches were performed between January, 2023 and March, 2023. Studies focused on female patients suffering simultaneously from Type II Diabetes Mellitus and fertility complications. Ten papers that met criteria were appraised and included.

Results:

There is evidence to suggest a causative relationship between the gut microbiome and reproductive functioning. Infertile patients had increased abundance of the phylum Verrucomicrobia and Phascolarctobacterium in the gastrointestinal tract, and decreased amounts of genera Stenotrophomonas, Streptococcus, and Roseburia. These abnormalities were associated with depleted circulating oestrogen concentrations, irregular menstrual cycling, and hyperandrogenism.

Evidence authenticates the use of probiotics and hormone therapy in treatment of Type II Diabetes and its associated symptoms. Supplements studied included metformin, GIP agonists, and GLP-1 receptors. Across studies, patients showed significant improvements in Type II Diabetes management following treatment.

Conclusion

Alterations to the composition of the gut microbiome are associated with improvements in glycemic control as well as improvements in fertility in female patients with Type II Diabetes Mellitus.

References

Baker, J.M., Al-Nakkash, L. and Herbst-Kralovetz, M.M. (2017). Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas, [online] 103, pp.45–53. doi:https://doi.org/10.1016/j.maturitas.2017.06.025.

Cheah, S., Gao, Y., Mo, S., Rigas, G., Fisher, O., Chan, D.L., Chapman, M.G. and Talbot, M.L. (2022). Fertility, pregnancy and post partum management after bariatric surgery: a narrative review. Medical Journal of Australia, 216(2), pp.96–102. doi:https://doi.org/10.5694/ mja2.51373.

Christ, J.P. and Falcone, T. (2018). Bariatric Surgery Improves Hyperandrogenism, Menstrual Irregularities, and Metabolic Dysfunction Among Women with Polycystic Ovary Syndrome (PCOS). Obesity Surgery, 28(8), pp.2171–2177. doi:https://doi.org/10.1007/s11695- 018-3155-6.

Diabetes Ireland. (n.d.). Diabetes Prevalence in Ireland. [online] Available at: https://www.diabetes.ie/about-us/ diabetes-in-ireland/#:~:text=537%20million%20 adults%20 [Accessed 26 Feb. 2023].

Diabetes.co.uk (2023). Fertility and Diabetes. [online] Diabetes.co.uk. Available at: https://www.diabetes. co.uk/pregnancy-complications/fertility-and-diabetes. html#:~:text=Common%20causes%20of%20 infertility%20in%20women&text=Women%20who%20 have%20diabetes%20are [Accessed 19 Mar. 2023].

Jensterle, M., Janez, A., Fliers, E., DeVries, J.H., Vrtacnik-Bokal, E. and Siegelaar, S.E. (2019). The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective. Human Reproduction Update, [online] 25(4), pp.504–517. doi:https://doi. org/10.1093/humupd/dmz019.

Khalili, L., Alipour, B., Jafar-Abadi, M.A., Faraji, I., Hassanalilou, T., Abbasi, M.M., Vaghef-Mehrabany, E. and Sani, M.A. (2019). The Effects of Lactobacillus casei on Glycemic Response, Serum Sirtuin1 and Fetuin-A Levels in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial. Iranian Biomedical Journal, [online] 23(1), pp.68–77. doi:https://doi.org/10.29252/.23.1.68.

Khan, D., Ojo, O.O., Woodward, O.R., Lewis, J.E., Sridhar, A., Gribble, F.M., Reimann, F., Flatt, P.R. and Moffett, R.C. (2022). Evidence for Involvement of GIP and GLP-1 Receptors and the Gut-Gonadal Axis in Regulating Female Reproductive Function in Mice. Biomolecules, [online] 12(12), p.1736. doi:https://doi.org/10.3390/ biom12121736.

Komiya, S., Naito, Y., Okada, H., Matsuo, Y., Hirota, K., Takagi, T., Mizushima, K., Inoue, R., Abe, A. and Morimoto, Y. (2020). Characterizing the gut microbiota in females with infertility and preliminary results of a watersoluble dietary fiber intervention study. Journal of Clinical Biochemistry and Nutrition, [online] 67(1), pp.105–111. doi:https://doi.org/10.3164/jcbn.20-53.

Lee, R., Mathew, C.J., Jose, M.T., Elshaikh, A.O., Shah, L. and Cancarevic, I. (2020). A Review of the Impact of Bariatric Surgery in Women With Polycystic Ovary Syndrome. Cureus, [online] 12(10). doi:https://doi. org/10.7759/cureus.10811.

Livshits, A. and Seidman, D.S. (2009). Fertility Issues in Women with Diabetes. Women’s Health, 5(6), pp.701– 707. doi:https://doi.org/10.2217/whe.09.47.

Mattsson, K., Nilsson-Condori, E., Elmerstig, E., Vassard, D., Schmidt, L., Ziebe, S. and Jöud, A. (2021). Fertility outcomes in women with pre-existing type 2 diabetes—a prospective cohort study. Fertility and Sterility, 116(2), pp.505–513. doi:https://doi.org/10.1016/j. fertnstert.2021.02.009.

Mayo Clinic (2023). Bariatric surgery. [online] www. mayoclinic.org. Available at: https://www.mayoclinic. org/tests-procedures/bariatric-surgery/about/ pac-20394258#:~:text=Gastric%20bypass%20and%20 other%20weight.

Moxthe, L.C., Sauls, R., Ruiz, M., Stern, M., Gonzalvo, J. and Gray, H.L. (2020). Effects of Bariatric Surgeries on Male and Female Fertility: A Systematic Review. Journal of Reproduction & Infertility, [online] 21(2), pp.71– 86. Available at: https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC7253939/.

NHS (2024). Why weight loss surgery is done. [online] nhs.uk. Available at: https://www.nhs.uk/conditions/ weight-loss-surgery/why-its-done/.

Public Health England (2014). Obesity and Type 2 Diabetes. Practical Diabetes International, [online] 18(8), pp.263–264. doi:https://doi.org/10.1002/pdi.261.

Qi, X., Yun, C., Pang, Y. and Qiao, J. (2021). The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes, [online] 13(1), p.1894070. doi:https://doi.org/10.1080/19490976.202 1.1894070.

Rittiphairoj, T., Pongpirul, K., Janchot, K., Mueller, N.T. and Li, T. (2020). Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Advances in Nutrition, 12(3). doi:https://doi.org/10.1093/advances/nmaa133.

Rosenstock, J., Wysham, C., Frías, J.P., Kaneko, S., Lee, 23 C.J., Fernández Landó, L., Mao, H., Cui, X., Karanikas, C.A. and Thieu, V.T. (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a doubleblind, randomised, phase 3 trial. The Lancet, 398(10295), pp.143–155. doi:https://doi.org/10.1016/s0140- 6736(21)01324-6.

Salles, B.I.M., Cioffi, D. and Ferreira, S.R.G. (2020). Probiotics supplementation and insulin resistance: a systematic review. Diabetology & Metabolic Syndrome, [online] 12(1), p.98. doi:https://doi.org/10.1186/ s13098-020-00603-6.

Shyangdan, D.S., Royle, P.L., Clar, C., Sharma, P. and Waugh, N.R. (2010). Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and metaanalysis. BMC Endocrine Disorders, 10(1). doi:https:// doi.org/10.1186/1472-6823-10-20.

Ulker, I. and Yildiran, H. (2019). The effects of bariatric surgery on gut microbiota in patients with obesity: a review of the literature. Bioscience of Microbiota, Food and Health, 38(1), pp.3–9. doi:https://doi.org/10.12938/ bmfh.18-018.

Williams, D. and Kreider, K.E. (2021). Type 2 diabetes in women of reproductive age. [online] Women’s Healthcare. Available at: https://www. npwomenshealthcare.com/type-2-diabetes-in-womenof-reproductive-age/#:~:text=The%20prevalence%20 of%20diabetes%20mellitus.

World Health Organization (n.d.). Indicator Metadata Registry Details. [online] www.who.int. Available at: https://www.who.int/data/gho/indicator-metadataregistry/imr-details/women-of-reproductive-age-(15-49- years)-population-(thousands)#:~:text=Definition%3A [Accessed 26 Feb. 2023].