The Effects of Acetyl-L-Carnitine and Myo/Chiro-Inositol in Patients With PCOS

Summary

The large number of women in their child bearing age is affected by Polycystic ovarian syndrome (PCOS) leading to infertility. However it is considered as a multisystem disorder with comorbidities rather than a gynecological and a dermatological problem. Patient mostly have anovulation presented as oligomennorhea or amenorrhea and hyperandrogenism presented as hirsutism along with hyperinsulinemia and insulin resistance. Many etiological factors are reported but those actually responsible for PCOS in females still need to be explored. However hyperandrogenism and insulin resistance being the key triggering condition apart from cardiovascular disease, type 2 diabetes, hypertension and obesity. World Health Organization (WHO) has considered Infertility's as public health problem. Researchers reported the obesity role in occurrence of PCOS and its Infertility's relation . PCOS is not a simple pathophysiologic process for which one treatment address all manifestation. Treatment should target specific manifestations and individualized patient goals. First-line agents for ovulation induction and treatment of infertility in patients with PCOS include metformin and clomiphene alone or in combination. It has been approved as category "A "to regulate ovulation and improves pregnancy rates in women with PCOS . Mostly it result in complication like multiple follicle recruitment rate, multiple pregnancy and thinning of endometrial wall leading to early abortion and endometrial cancers. The use of naturally occurring compounds like myoinositol, D-chiro- inositol and L- carnitine which are already part of human body are expected to produce significant results without any side effects . The proposed study will provide an alternative to current treatments available for infertility due to PCOS. The expected project execution time is 2 years. Thus, the present project will discover new insights about treatment of infertility and thus generate new knowledge which will help Academia, scientists and health care professionals. Results of the study will be disseminated on different forums including to policy makers , Pharmaceutical, national and international agencies. The result will be published in journal both national and international with good impact factors. The outcome of the project will be used as publication in high impact international journals, filling of patents and will also be presented in national and international forums.

Timeline

Start

2023-07-15

Primary completion

2024-02-25

Completion

2024-03-10

Publications

• Background Rubin KH, Glintborg D, Nybo M, Abrahamsen B, Andersen M. Development and Risk Factors of Type 2 Diabetes in a Nationwide Population of Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3848-3857. doi: 10.1210/jc.2017-01354.
• Background Orio F, Palomba S. Reproductive endocrinology: New guidelines for the diagnosis and treatment of PCOS. Nat Rev Endocrinol. 2014 Mar;10(3):130-2. doi: 10.1038/nrendo.2013.248. Epub 2013 Dec 10.
• Background Akram M, Roohi N. Endocrine correlates of polycystic ovary syndrome in Pakistani women. J Coll Physicians Surg Pak. 2015 Jan;25(1):22-6.
• Background Chauhan B, Kumar G, Kalam N, Ansari SH. Current concepts and prospects of herbal nutraceutical: A review. J Adv Pharm Technol Res. 2013 Jan;4(1):4-8. doi: 10.4103/2231-4040.107494.
• Background An H, He L. Current understanding of metformin effect on the control of hyperglycemia in diabetes. J Endocrinol. 2016 Mar;228(3):R97-106. doi: 10.1530/JOE-15-0447. Epub 2016 Jan 7.
• Background Mansfield R, Galea R, Brincat M, Hole D, Mason H. Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril. 2003 Apr;79(4):956-62. doi: 10.1016/s0015-0282(02)04925-7.
• Background Morley LC, Tang T, Yasmin E, Norman RJ, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2017 Nov 29;11(11):CD003053. doi: 10.1002/14651858.CD003053.pub6.
• Background Tauqir S, Israr M, Rauf B, Malik MO, Habib SH, Shah FA, Usman M, Raza MA, Shah I, Badshah H, Ehtesham E, Shah M. Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial. Adv Ther. 2021 Jul;38(7):3842-3856. doi: 10.1007/s12325-021-01789-5. Epub 2021 May 28.
• Background Salehpour S, Nazari L, Hoseini S, Moghaddam PB, Gachkar L. Effects of L-carnitine on Polycystic Ovary Syndrome. JBRA Assist Reprod. 2019 Oct 14;23(4):392-395. doi: 10.5935/1518-0557.20190033.
• Background 10. Porcaro G, Bizzarri M, Monastra G, et al Strategies for the treatment of polycystic ovary syndrome (PCOS) women: the role of myoinositol (MI) and d-chiro-inositol (DCI) between diet and therapy. Nova science publishers. 2016 1-18
• Background 11. Facchinetti F, Dante G, Neri I. The ratio of MI to DCI and its impact in the treatment of polycystic ovary syndrome: experimental and literature evidences. Front Gynecol Endocrinol 2015;3:103-9.
• Background Heimark D, McAllister J, Larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr J. 2014;61(2):111-7. doi: 10.1507/endocrj.ej13-0423. Epub 2013 Nov 2.
• Background Bevilacqua A, Bizzarri M. Inositols in Insulin Signaling and Glucose Metabolism. Int J Endocrinol. 2018 Nov 25;2018:1968450. doi: 10.1155/2018/1968450. eCollection 2018.
• Gul M, Khan H, Rauf B, Bukhari SMS, Ehtesham E, Malik MO, Shah FA, Alanazi FE, Shah M. Comparative efficacy of combined myo-inositol and D-chiro inositol versus metformin across PCOS Phenotypes: enhancing ovarian function, ovulation, and stress response in a prospective clinical trial. Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul;398(7):8761-8772. doi: 10.1007/s00210-025-03813-9. Epub 2025 Jan 23.

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