l-Carnitine plus metformin in clomiphene-resistant obese PCOS women, reproductive and metabolic effects: a randomized clinical trial

Gynecological Endocrinology

Volumn 35, Issue 8, 2019, Pages 701-705

  El Sharkwy, Ibrahim ^a   Sharaf El Din, Mostafa ^b  

^a ZAGAZIG UNIVERSITY   (Egypt)

^b ZAGAZIG UNIVERSITY   (Egypt)

Author keywords

l Carnitine; metabolic effect; metformin; obese; polycystic ovary syndrome; reproductive effect

Indexed keywords

CARNITINE; CLOMIFENE CITRATE; FOLLITROPIN; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LUTEINIZING HORMONE; METFORMIN; TESTOSTERONE; TRIACYLGLYCEROL; CLOMIFENE; FERTILITY PROMOTING AGENT; HORMONE;

ADULT; ARTICLE; BODY MASS; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; FEMALE; FIRST TRIMESTER PREGNANCY; FOLLOW UP; HUMAN; INSULIN RESISTANCE; LIPID FINGERPRINTING; MAJOR CLINICAL STUDY; MENSTRUAL CYCLE; METABOLIC REGULATION; OBESITY; OVARY POLYCYSTIC DISEASE; OVULATION; PREGNANCY RATE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REPRODUCTIVE SUCCESS; SPONTANEOUS ABORTION; TRANSVAGINAL ECHOGRAPHY; COMPLICATION; DRUG EFFECT; DRUG RESISTANCE; FEMALE INFERTILITY; GLUCOSE BLOOD LEVEL; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; REPRODUCTION; TREATMENT OUTCOME; YOUNG ADULT;

ADULT; BLOOD GLUCOSE; CARNITINE; CLOMIPHENE; DRUG RESISTANCE; FEMALE; FERTILITY AGENTS, FEMALE; HORMONES; HUMANS; INFERTILITY, FEMALE; INSULIN RESISTANCE; METFORMIN; OBESITY; POLYCYSTIC OVARY SYNDROME; PREGNANCY; PREGNANCY RATE; REPRODUCTION; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85062342157     PISSN: 09513590     EISSN: 14730766     Source Type: Journal    
DOI: 10.1080/09513590.2019.1576622     Document Type: Article

References (42)

1. Hu L, Shen H, Wu QF, et al. Treatment of polycystic ovarian syndrome with insulin resistance by insulin-sensitizer. Clin Exp Obstet Gynecol. 2014;41:288–292.
2. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2014;6:1–13.
3. Valsamakis G, Lois K, Kumar S, et al. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS). Hormones (Athens). 2013;12:363–378.
4. Cho LW, Kilpatrick ES, Keevil BG, et al. Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome. Clin Endocrinol (Oxf). 2009;70:233–237.
5. Behboudi-Gandevani S, Ramezani Tehrani F, Rostami Dovom M, et al. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies. Gynecol Endocrinol. 2016;32:343–353.
6. Barber TM, Dimitriadis GK, Andreou A, et al. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance. Clin Med (Lond). 2016;16:262–266.
7. Roe A, Hillman J, Butts S, et al. Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS. J Clin Endocrinol Metab. 2014;99:E841–E847.
8. Katsiki N, Hatzitolios AI. Insulin-sensitizing agents in the treatment of polycystic ovary syndrome: an update. Curr Opin Obstet Gynecol. 2010;22:466–476.
9. Johnson N. Metformin is a reasonable first-line treatment option for non-obese women with infertility related to anovulatory polycystic ovary syndrome–a met analysis of randomized trials. Aust N Z J Obstet Gynecol. 2011;51:125–129.
10. El-Hattab AW, Scaglia F. Disorders of carnitine biosynthesis and transport. Mol Genet Metab. 2015;116:107–112.
11. Ringseis R, Eder K, Keller J. Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. Eur J Nutr. 2012;51:1–18.
12. Fenkci SM, Fenkci V, Oztekin O, et al. Serum total l-carnitine levels in non-obese women with polycystic ovary syndrome. Hum Reprod. 2008;23:1602–1606.
13. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19:41–47.
14. Brown J, Farquhar C, Beck J, et al. Clomiphene and antiestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009;4:CD002249.
15. Ismail AM, Hamed AH, Saso S, et al. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2014;180:148–152.
16. Tang T, Glanville J, Hayden CJ, et al. Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome: a randomized, placebo controlled, double-blind multicenter study. Hum Reprod. 2006;21:80–89.
17. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Res. 2012;33:981–1030.
18. Bjelica A, Bjelanović J, Milić N, et al. Algorithm of ovulation induction in patients with polycistic ovary syndrome. Med Pregl. 2016;69:25–30.
19. Balen AH, Morley LC, Misso M, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22:687–708.
20. Legro RS. Ovulation induction in polycystic ovary syndrome: current options. Best Pract Res Clin Obstet Gynecol. 2016;37:152–159.
21. Costello MF, Misso ML, Wong J, et al. The treatment of infertility in polycystic ovary syndrome: a brief update. Aust N Z J Obstet Gynaecol. 2012;52:400–403.
22. Tagliaferri V, Romualdi D, Immediata V, et al. Metformin vs. myoinositol: which is better in obese polycystic ovary syndrome patients? A randomized controlled crossover study. Clin Endocrinol (Oxf). 2017;86:725–730.
23. Yang PK, Hsu CY, Chen MJ, et al. The efficacy of 24-month metformin for improving menses, hormones, and metabolic profiles in polycystic ovary syndrome. J Clin Endocrinol Metab. 2018;103:890–899.
24. Lord JM, Flight IH, Norman RJ. Insulin sensitizing drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev. 2003;3:CD003053.
25. Tan S, Hahn S, Benson S, et al. Metformin improves polycystic ovary syndrome symptoms irrespective of pre-treatment insulin resistance. Eur J Endocrinol. 2007;157:669–676.
26. Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A, et al. Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum Reprod Update. 2009;15:57–68.
27. Tang T, Lord JM, Norman RJ, et al. Insulin-sensitizing drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhea and subfertility. Cochrane Database Syst Rev. 2012;5:CD003053.
28. Shahebrahimi K, Jalilian N, Bazgir N, et al. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome. Indian J Endocr Metab. 2016;20:805–809.
29. Naderpoor N, Shorakae S, de Courten B, et al. Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis. Hum Reprod Update. 2015;2:560–574.
30. Patel R, Shah G. Effect of metformin on clinical, metabolic and endocrine outcomes in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2017;33:1545–1557.
31. Bredella MA, McManus S, Misra M. Impact of metformin monotherapy versus metformin with oestrogen-progesterone on lipids in adolescent girls with polycystic ovarian syndrome. Clin Endocrinol (Oxf). 2013;79:199–203.
32. Emami Naini A, Moradi M, Mortazavi M, et al. Effects of oral L-carnitine supplementation on lipid profile, anemia, and quality of life in chronic renal disease patients under hemodialysis: a randomized, double-blinded, placebo-controlled trial. J Nutr Metab. 2012;2012:510483.
33. Samimi M, Jamilian M, Ebrahimi FA, et al. Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf). 2016; 84:851–857.
34. Gao J, Zhou L, Hong J, et al. Assessment of insulin resistance in Chinese PCOS patients with normal glucose tolerance. Gynecol Endocrinol. 2017;4:1–4.
35. Zahra M, Shah M, Ali A, et al. Effects of metformin on endocrine and metabolic parameters in patients with polycystic ovary syndrome. Horm Metab Res. 2017;49:103–108.
36. Wall BT, Stephens FB, Constantin-Teodosiu D, et al. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol. 2011;589:963–973.
37. Ruggenenti P, van der Meer IM, Remuzzi G. Oral acetyl-L-carnitine therapy and insulin resistance. Hypertension. 2010;55:e26.
38. Ribas GS, Vargas CR, Wajner M. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene. 2014;533:469–476.
39. Kuşçu NK, Var A. Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome. Acta Obstet Gynecol Scand. 2009;88:612–617.
40. Jamilian H, Jamilian M, Samimi M, et al. Oral carnitine supplementation influences mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol. 2017;33:442–447.
41. Özer A, Bakacak M, Kıran H, et al. Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome. Ginekol Pol. 2016;87:733–738.
42. Celik F, Kose M, Yilmazer M, et al. Plasma L-carnitine levels of obese and non-obese polycystic ovary syndrome patients. J Obstet Gynaecol. 2017;37:476–479.