The use of inositol(s) isomers in the management of polycystic ovary syndrome: a comprehensive review

References

• Asuncion M , Calvo RM , San Millan JL , et al . A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000; 85:2434–8.
   PubMed Web of Science ®Google Scholar
• Knochenhauer ES , Key TJ , Kahsar-Miller M , et al . Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 1998;83:3078–82.
   PubMed Web of Science ®Google Scholar
• Group REA-SPCW . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19–25.
   Web of Science ®Google Scholar
• Monastra G , Unfer V , Harrath AH , et al . Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecol Endocrinol 2017;33:1–9.
   PubMed Web of Science ®Google Scholar
• Sun TH , Heimark DB , Nguygen T , et al . Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. Biochem Biophys Res Commun 2002;293:1092–8.
   PubMed Web of Science ®Google Scholar
• Nestler JE , Jakubowicz DJ , de Vargas AF , et al . Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998;83:2001–5.
   PubMed Web of Science ®Google Scholar
• Nestler JE , Unfer V. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol 2015;31:501–5.
   PubMed Web of Science ®Google Scholar
• Baillargeon JP , Diamanti-Kandarakis E , Ostlund RE Jr , et al . Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 2006;29:300–5.
   PubMed Web of Science ®Google Scholar
• Iuorno MJ , Jakubowicz DJ , Baillargeon JP , et al . Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 2002;8:417–23.
   PubMedGoogle Scholar
• Nestler JE , Jakubowicz DJ , Iuorno MJ. Role of inositolphosphoglycan mediators of insulin action in the polycystic ovary syndrome. J Pediatr Endocrinol Metab 2000;13(Suppl 5):1295–8.
   PubMed Web of Science ®Google Scholar
• Iuorno MJ , Nestler JE. Insulin-lowering drugs in polycystic ovary syndrome. Obstet Gynecol Clin North Am 2001;28:153–64.
   PubMed Web of Science ®Google Scholar
• Unfer V , Carlomagno G , Dante G , et al . Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. Gynecol Endocrinol 2012;28:509–15.
   PubMed Web of Science ®Google Scholar
• Galazis N , Galazi M , Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol 2011;27:256–62.
   PubMed Web of Science ®Google Scholar
• Baillargeon JP , Nestler JE , Ostlund RE , et al . Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum Reprod 2008;23:1439–46.
   PubMed Web of Science ®Google Scholar
• Cheang KI , Baillargeon JP , Essah PA , et al . Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metab Clin Exp 2008;57:1390–7.
   PubMed Web of Science ®Google Scholar
• Carlomagno G , Unfer V , Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril 2011;3095:2515–16.
   PubMed Web of Science ®Google Scholar
• Unfer V , Carlomagno G , Rizzo P , et al . Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Eur Rev Med Pharmacol Sci 2011;15:452–7.
   PubMed Web of Science ®Google Scholar
• Unfer V , Orrù B , Monastra G. Inositols: from physiology to rational therapy in gynecological clinical practice. Expert Opin Drug Metab Toxicol 2016;12:1129–31.
   PubMed Web of Science ®Google Scholar
• Facchinetti F , Bizzarri M , Benvenga S , et al . Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol 2015;195:72–6.
   PubMed Web of Science ®Google Scholar
• Unfer V , Carlomagno G , Papaleo E , et al . Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci 2014;21:854–8.
   PubMed Web of Science ®Google Scholar
• Harwood K , Vuguin P , DiMartino-Nardi J. Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Horm Res 2007;68:209–17.
   PubMed Web of Science ®Google Scholar
• Matalliotakis I , Kourtis A , Koukoura O , et al . Polycystic ovary syndrome: etiology and pathogenesis. Arch Gynecol Obstet 2006;274:187–97.
   PubMedGoogle Scholar
• Chattopadhayay R , Ganesh A , Samanta J , et al . Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecol Obstet Invest 2010;69:197–202.
   PubMed Web of Science ®Google Scholar
• Raffone E , Rizzo P , Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 2010;26:275–80.
   PubMed Web of Science ®Google Scholar
• Isabella R , Raffone E. Does ovary need D-chiro-inositol?. J Ovarian Res 2012;5:14.
   PubMed Web of Science ®Google Scholar
• Carlomagno G , Unfer V. Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci 2011;15:931–6.
   PubMed Web of Science ®Google Scholar
• Nestler JE , Jakubowicz DJ , Reamer P , et al . Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999;340:1314–20.
   PubMed Web of Science ®Google Scholar
• Dona G , Sabbadin C , Fiore C , et al . Inositol administration reduces oxidative stress in erythrocytes of patients with polycystic ovary syndrome. Eur J Endocrinol 2012;166:703–10.
   PubMed Web of Science ®Google Scholar
• Zacche MM , Caputo L , Filippis S , et al . Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol 2009;25:50813.
   PubMed Web of Science ®Google Scholar
• Genazzani AD , Lanzoni C , Ricchieri F , et al . Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 2008;24:139–44.
   PubMed Web of Science ®Google Scholar
• Minozzi M , Costantino D , Guaraldi C , et al . The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol 2011;27:920–4.
   PubMed Web of Science ®Google Scholar
• Minozzi M , D’Andrea G , Unfer V. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reprod Biomed Online 2008;17:579–82.
   PubMed Web of Science ®Google Scholar
• Artini PG , Di Berardino OM , Papini F , et al . Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol 2013;29:375–9.
   PubMed Web of Science ®Google Scholar
• Jamilian M , Farhat P , Foroozanfard F , et al . Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial. Clin Endocrinol 2017;87:194–200.
   PubMed Web of Science ®Google Scholar
• Venturella O , Mocciaro R , De Trana E , et al . Assesment of the modification of the clinical, endocrinal and metabolical profile of patients with PCOS syndrome treated with Myo-inositol. MinervaGinecol 2010;64:239–43.
   Google Scholar
• Kamenov Z , Kolarov G , Gateva A , et al . Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol 2015;31:131–5.
   PubMed Web of Science ®Google Scholar
• Gerli S , Mignosa M , Di Renzo GC. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2003;7:151–9.
   PubMedGoogle Scholar
• Ozay AC , Emekci Ozay O , Okyay RE , et al . Different effects of myoinositol plus folic acid versus combined oral treatment on androgen levels in PCOS women. Int J Endocrinol 2016;2016:3206872.
   PubMed Web of Science ®Google Scholar
• Benelli E , Del Ghianda S , Di Cosmo C , et al . A combined therapy with myo-inositol and D-chiro-inositol improves endocrine parameters and insulin resistance in PCOS young overweight women. Int J Endocrinol 2016;2016:3204083.
   PubMed Web of Science ®Google Scholar
• Costantino DMG , Minozzi E , Guaraldi C . Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci 2009;13:105–10.
   PubMed Web of Science ®Google Scholar
• Gerli S , Papaleo E , Ferrari A , et al . Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci 2007;11:347–54.
   PubMed Web of Science ®Google Scholar
• Genazzani AD , Prati A , Santagni S , et al . Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol 2012;28:969–73.
   PubMed Web of Science ®Google Scholar
• Pkhaladze L , Barbakadze L , Kvashilava N. Myo-inositol in the treatment of teenagers affected by PCOS. Int J Endocrinol 2016;2016:1473612.
   PubMed Web of Science ®Google Scholar
• D'Anna R , Di Benedetto V , Rizzo P , et al . Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol 2012;28:440–2.
   PubMed Web of Science ®Google Scholar
• Corrado F , D’Anna R , Di Vieste G , et al . The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med 2011;28:972–5.
   PubMed Web of Science ®Google Scholar
• Santamaria A , Di Benedetto A , Petrella E , et al . Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med 2016;29:3234–7.
   PubMed Web of Science ®Google Scholar
• D'Anna R , Di Benedetto A , Scilipoti A , et al . Myo-inositol supplementation for prevention of gestational diabetes in obese pregnant women: a randomized controlled trial. Obstet Gynecol 2015;126:310–15.
   PubMed Web of Science ®Google Scholar
• Lubin V , Shojai R , Darmon P , et al . A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin. Diabetes Metab 2016;42:192–5.
   PubMed Web of Science ®Google Scholar
• Zheng X , Liu Z , Zhang Y , et al . Relationship between myo-inositol supplementary and gestational diabetes mellitus: a meta-analysis. Medicine (Baltimore) 2015;94:e1604.
   PubMed Web of Science ®Google Scholar
• Brown J , Crawford TJ , Alsweiler J , et al . Dietary supplementation with myo-inositol in women during pregnancy for treating gestational diabetes. Cochrane Database Syst Rev 2016;9:CD012048.
   Web of Science ®Google Scholar
• Minozzi M , Nordio M , Pajalich R. The combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci 2013;17:537–40.
   PubMed Web of Science ®Google Scholar
• Nordio M , Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci 2012;16:575–81.
   PubMed Web of Science ®Google Scholar
• Pintaudi B , Di Vieste G , Bonomo M. The effectiveness of myo-inositol and D-chiro inositol treatment in type 2 diabetes. Int J Endocrinol 2016;2016:9132052.
   PubMed Web of Science ®Google Scholar
• Farren M , Daly N , McKeating A , et al . The prevention of gestational diabetes mellitus with antenatal oral inositol supplementation: a randomized controlled trial. Diabetes Care 2017;40:759–63.
   PubMed Web of Science ®Google Scholar
• Papaleo E , Unfer V , Baillargeon JP , et al . Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol 2007;23:700–3.
   PubMed Web of Science ®Google Scholar
• Papaleo E , Unfer V , Baillargeon JP , et al . Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 2009;91:1750–4.
   PubMed Web of Science ®Google Scholar
• Ciotta LII , Rubbino G , Iemmola A , et al . Treatment of hyperandrogenism by Myo-inositol. 14th World Congress of Gynecological Endocrinology. 2010.
   Google Scholar
• Papaleo EDSL , Baillargeon J , Zacche M , et al . Comparison of Myo-inositol plus folic acid vs clomiphene citrate for first line treatment in women with polycystic ovary syndrome., Barcelona. O-251 [24th Annual meeting of ESHRE]. 2008 6–9 July.
   Google Scholar
• Morgante G , Orvieto R , Di Sabatino A , et al . The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen. Fertil Steril 2011;3095:2642–4.
   PubMed Web of Science ®Google Scholar
• Regidor PA , Schindler AE. Myoinositol as a safe and alternative approach in the treatment of infertile PCOS women: a German observational study. Int J Endocrinol 2016;2016:9537632.
   PubMed Web of Science ®Google Scholar
• Le Donne M , Alibrandi A , Giarrusso R , et al . [Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition]. Minerva Ginecol 2012;64:23–9.
   PubMedGoogle Scholar
• Chiu TT , Rogers MS , Briton-Jones C , et al . Effects of myo-inositol on the in-vitro maturation and subsequent development of mouse oocytes. Hum Reprod 2003;18:408–16.
   PubMed Web of Science ®Google Scholar
• Chiu TT , Rogers MS , Law EL , et al . Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 2002;17:1591–6.
   PubMed Web of Science ®Google Scholar
• Bevilacqua A , Carlomagno G , Gerli S , et al . Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology–assisted reproduction technology. Gynecol Endocrinol 2015;31:441–6.
   PubMed Web of Science ®Google Scholar
• Ciotta L , Stracquadanio M , Pagano I , et al . Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 2011;15:509–14.
   PubMed Web of Science ®Google Scholar
• Wdowiak A. Myoinositol improves embryo development in PCOS patients undergoing ICSI. Int J Endocrinol 2016;2016:6273298.
   PubMed Web of Science ®Google Scholar
• Lisi F , Carfagna P , Oliva MM , et al . Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reprod Biol Endocrinol 2012;2310:52.
   PubMed Web of Science ®Google Scholar
• Rizzo P , Raffone E , Benedetto V. Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci 2010;14:555–61.
   PubMed Web of Science ®Google Scholar
• Unfer V , Raffone E , Rizzo P , et al . Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol 2011;27:857–61.
   PubMed Web of Science ®Google Scholar
• Colazingari STM , Najjar R , Bevilacqua A. Treatment of hyperandrogenism by Myo-inositol: results from a randomized controlled trial. Arch Gynecol Obstet 2013;11:1405.
   Web of Science ®Google Scholar
• Montanino Oliva M , Poverini R , Lisi R , et al . Treating woman with myo-inositol vaginal suppositories improves partner’s sperm motility and fertility. Int J Endocrinol 2016;2016:7621942.
   PubMed Web of Science ®Google Scholar