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(12):969-973.
An uncontrolled prospective study. All participants received the same treatment.
Forty-two overweight women with polycystic ovarian syndrome (PCOS) were selected from the University of Modena’s Gynecological Endocrinology Center in Italy. Participants were included if they had polycystic ovarian morphology on ultrasonography, mild to severe hirsutism and/or acne, oligomenorrhea or amenorrhea, a body mass index (BMI) greater than 25.5 m/kg, and normal prolactin levels. Participants were excluded if they had any other endocrine disorder or if they were on any hormonal treatment in the last 6 months.
Study Medication and Treatment Protocol
Study participants were divided into 2 groups based on their baseline fasting insulin levels. Participants in group A (n=15) had insulin below 12 µU/mL; participants in group B (n=27) had insulin above 12 µU/mL. All participants took myo-inositol (2 grams) and folic acid (200 mcg) dissolved in water between 9 am and 11 am daily for 8 weeks. No dietary or lifestyle modifications to improve insulin sensitivity were recommended during the study.
Primary Outcome Measures
BMI, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol, progesterone, androstenedione, testosterone, dehydroepiandrosterone sulfate (DHEA-S), glucose, C-peptide, oral glucose tolerance, and insulin levels were measured at baseline and at 8 weeks. Insulin sensitivity was calculated as a glucose-to-insulin ratio since this has been shown to be a valid marker of insulin sensitivity in women with PCOS.1
After the 8-week myo-inositol treatment, there was a significant reduction in LH/FSH ratio, FSH, prolactin, androstenedione, testosterone, insulin, and BMI compared to baseline; there was also a significant increase in the glucose/insulin ratio (8.4±0.9 to 12.1±0.2, P<0.01). In consideration of baseline fasting insulin levels, myo-inositol treatment induced similar changes in both groups but only patients in group B demonstrated significant reduction in fasting insulin levels (20.3±1.8 to 12.9±1.8 µU/mL, P<0.00001). No side effects or adverse events were observed in any of the study participants; however, a prior study demonstrated that when myo-inositol was dosed at 12 grams per day, patients experienced gastrointestinal distress like nausea, diarrhea, and flatulence.2
Over the last decade, myo-inositol has been used more and more as a natural insulin sensitizer.
PCOS is one of the most common endocrine disorders, affecting up to 20% of women of reproductive age.3 The diagnostic criteria for PCOS include chronic oligomenorrhea or anovulation, hyperandrogenism, and polycystic ovarian morphology.4 PCOS is associated with an increased risk of developing hypertension, dyslipidemia, type 2 diabetes, and heart disease.5–7 Insulin resistance is another common feature of PCOS in both overweight and lean women,8 and it is often treated with insulin sensitizers like metformin.9,10 Over the last decade, myo-inositol, an isomerized and dephosphorylated precursor of glucose-6-phosphate, has been used more and more as a natural insulin sensitizer. The role of myo-inositol in the pathophysiology of PCOS has been the focus of recent studies. It has been suggested that insulin resistance in PCOS women can be attributed to a deficiency of myo-inositol’s intracellular metabolites, D-chiro-inositol (DCI) and inositol-phosphoglycan (IPG), mediators of insulin action.11–14 It has also been postulated that patients with PCOS have a higher urinary clearance of DCI.15 In addition to its role in insulin sensitivity, DCI functions as an intracellular messenger in mammalian oocytes, playing a role in the follicular milieu, meiotic resumption, and oocyte maturation.16,17
Treating women with myo-inositol or DCI has been shown to reduce androgen levels, help restore ovulatory function, lower blood pressure, and decrease triglyceride levels.18,19 This study confirms prior studies that have shown that myo-inositol or DCI administration improves endocrine parameters and insulin sensitivity, more so in women with higher fasting insulin levels, defined by a fasting insulin level greater than 12 µU/mL.20 Although weight loss and dietary interventions are also known to improve insulin sensitivity and hyperandrogenism and restore ovation in women with PCOS, 21– 23 studies investigating the potentially additive benefit of combining lifestyle interventions with myo-inositol would be beneficial. Myo-inositol is a safe and effective natural medicine for improving insulin resistance and it should be recommended in conjunction with other positive lifestyle modifications for the management of PCOS and insulin resistance.
- Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1998;83(8):2694–2698.
- Carlomagno G, Unfer V: Inositol safety: clinical evidences. Eur Rev Med Pharmacol Sci. 2011;15(8):931–936.
- Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. 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(9): 3078–3082.
- Rotterdam ESHRE/ASRM-Sponsored PCOS wonsensus workshop group, Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004; 19(1): 41–47.
- Vrbikova J, Hainer V. Obesity and polycystic ovary syndrome. Obes Facts. 2009; 2(1): 26–35.
- Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999;84(1):165–169.
- Cattrall FR, Healy DL. Long-term metabolic, cardiovascular and neoplastic risks with polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):803–812.
- Zawadsky JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, editors. Current Issues in Endocrinology and Metabolism: Polycystic Ovary Syndrome. Cambridge, UK: Blackwell Scientific Publications; 1992: 377–384.
- De Leo V, la Marca A, Petraglia F. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev. 2003;24(5):633–667.
- Genazzani AD, Ricchieri F, Lanzoni C. Use of metformin in the treatment of polycystic ovary syndrome. Womens Health (Lond Engl). 2010;6:577–593.
- Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM. Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol. 2008;24:139–144.
- Baillargeon JP, Nestler JE, Ostlund RE, Apridonidze T, Diamanti-Kandarakis E. Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum Reprod. 2008;23(6):1439–1446.
- Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999;340(17):1314–1320.
- Romero G, Larner J. Insulin mediators and the mechanism of insulin action. Adv Pharmacol. 1993;24:21–50.
- Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE Jr, Apridonidze T, Iuorno MJ, Nestler JE. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care. 2006;29(2):300-305.
- Aouameur R, Da Cal S, Bissonnette P, Coady MJ, Lapointe JY: SMIT2 mediates all myo-inositol uptake in apical membranes of rat small intestine. Am J Physiol Gastrointest Liver Physiol. 2007;293(6):G1300–1307.
- Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ: Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod. 2002;17(6):1591–1596.
- 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(6):151–159.
- Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F. Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci. 2011;15(5):509-514.
- 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(12):969-973.
- Thomson RL, Buckley JD, Brinkworth GD. Exercise for the treatment and management of overweight women with polycystic ovary syndrome: a review of the literature. Obes Rev. 2011; 12: e202–e210.
- Marsh KA, Steinbeck KS, Atkinson FS, et al. Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr. 2010;92(1): 83–92.
- Moran LJ, Noakes M, Clifton PM, Wittert GA, Williams G, Norman RJ. Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome. Am J Clin Nutr. 2006;84(1):77–87.