Table 1.
Intervention studies with myo-inositol (MI), D-chiro-inositol (DCI) and a combination of DCI and MI in women affected by PCOS.
| Outcomes |
||||||||
|---|---|---|---|---|---|---|---|---|
| Reference | Study design | Treatment | N. of subjects | BMI | Hormonal | Insulin Resistance | Reproductive | |
| MI | ||||||||
| Artini et al., 2013 | RCT | MI 2 g/day + FA 200 mg/day No other drug treatment | 50 | 26.5 ± 6.1 | Reduction of plasma LH, PRL, T, insulin, and LH/FSH | Reduction | NA | |
| Ciotta et al., 2011 | RCT | MI 2 g/twice a day + FA 200 mcg/twice a day COH | 34 | NA | Reduction in total rFSH units and in E2 | NA | Increase number of mature oocytes; higher mean number of transferred embryos | |
| Costantino et al., 2009 | RCT | MI 4 g/day + FA 400 mcg/day No other drug treatment | 42 | 22.8 ± 0.3 | Decrease of serum free T | Reduction; improvement of glucose tolerance and reduction of glucose stimulated insulin release | NA | |
| Genazzani et al., 2008 | RCT | MI 2g/day + 2 mcg FA No other drug treatment | 20 | 29 ± 1.6 | Reduction in LH, PRL, T, insulin, and LH/FSH | Reduction | Restoration of menstrual cyclicity | |
| Genazzani et al., 2012 | Observational | MI 2 g/day No other drug treatment | 42 | 31.1 ± 1.4 | Reduction of LH, LH/FSH, and insulin | Reduction | NA | |
| Gerli et al., 2007 | RCT | MI 4 g/day + FA 400 mcg/day No other drug treatment | 92 | 34.0 (CI: 31.5–36.5) | Increase of E2 | No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge | Higher ovulation frequency, shorter time to first ovulation and more rapid follicular maturation | |
| Minozzi et al., 2008 | Open-label | MI 2 g/twice a day No other drug treatment | 46 | 27.5 | Reduction of total androgens, FSH and LH; increase of oestradiol | Reduction | NA | |
| Minozzi et al., 2011 | Prospective open-label | OCP + MI 4 g/day No other drug treatment | 155 | 26.7 ± 2.7 | Reduction of androgens | Reduction | NA | |
| Pacchiarotti et al., 2016 | RCT | Group A: MI 4 g/day + FA 400 mcg/day + melatonin 3 mg/day Group B: MI 4 g/day + FA 400 mcg/day COH | 526 | 22.8 ± 1.3 | Less total gonadotropin dose administered in group A versus B | NA | Increased number of mature oocytes and increased percentage of grade I embryos in group A versus group B | |
| Papaleo et al., 2007 | RCT | MI 2 g/twice a day + FA 400 mcg/day No other drug treatment | 25 | 28.5 ± 2.4 | NA | NA | Restoration of menstrual cyclicity, increase rates of pregnancies | |
| Raffone et al., 2010 | RCT | MI 4 g/day + FA 400 mcg/day or metformin 1500 mg/day | 120 | 25 ± 2.1 | NA | Reduction | Restored spontaneous ovulation activity and menstrual cycle | |
| Rago et al., 2015 | Pilot study | MI + α-LA IVF | 65 | NA | NA | Reduction | Number of transferred embryos Clinical pregnancy | |
| Sacchinelli et al., 2014 | Prospective | MI 4 g/day + NAC + FA 400 mcg/day No other drug treatment | 91 | 29.2 ± 2.21 | NA | Reduction of HOMA | Increase in ovulation | |
| DCI | ||||||||
| Cianci et al., 2015 | Prospective | DCI 1 g/day + LA 600 mg/day No other drug treatment | 46 | 28.7 ± 2 | Reduction of insulin | Reduction | Restoration of menstrual cyclicity | |
| Genazzani et al., 2014 | Observational | DCI 500 mg/day No other drug treatment | 22 | 31.5 ± 0.8 | Improvement in LH, LH/FSH, androstenedione, GnRH | Reduction | NA | |
| Iuorno et al., 2002 | Observational | DCI 600 mg/day No other drug treatment | 20 | 22.4 ± 0.3 | Decrease of serum T | Decrease of the insulin AUC | Restored ovulation activity | |
| La Marca et al., 2015 | Retrospective | DCI 1-1.5 g/day No other drug treatment | 47 | 23 ± 4.1 | Reduction of AMH | Reduction | Increase in regular menstrual cycles | |
| Laganà et al., 2015 | Observational | DCI 1 gr/day + FA 400 mcg/day No other drug treatment | 48 | 24.87 ± 5.21 | Reduction of LH, LH/FSH ratio, total and free T, ?-4-androstenedione and increase of SHBG | Reduction of HOMA and increase of glycemia/IRI ratio | Restoration of menstrual cyclicity | |
| Nestler et al., 1999 | RCT | DCI 1.2 g/day No other drug treatment | 44 | 31.3 ± 2.4 | Decrease of serum free T | Decrease of insulin AUC | Restored ovulation activity | |
| Piomboni et al., 2014 | RCT | Group A: DCI 1g/day + COH Group B: metformin 1.7 g/day + COH | 68 | 25.2 ± 4.1 | NA | NA | Improved oocyte quality | |
| MI+DCI | ||||||||
| Colazingari et al., 2013 | RCT | Group A: MI 550 mg/twice day + DCI 13.8 mg/twice a day Group B: DCI 500 mg/twice a day COH | 100 | <28 | Reduction in total rFSH units and in peak E2 levels | NA | Group B: increase number and quality of oocytes. Group A: higher fertilization rate and embryo quality; greater number of transferred embryos. | |
| Minozzi et al., 2013 | Longitudinal | MI 550 mg + DCI 13.8 mg twice a day No other drug treatment | 20 | 33.71 ± 6.1 | Improvement in LDL, HDL, and triglycerides levels | Reduction | NA | |
| Nordio and Proietti, 2012 | RCT | Group A: MI 2 g/twice a day Group B: MI 550 mg/twice a day + DCI 13,8 mg/twice a day | 50 | 27.5 ± 2.9 | Reduction of total T and increment of SHBG higher in group B compared to A | Reduction in glucose and insulin levels in group B | Restored ovulation activity | |
AMH, anti-müllerian hormone; AUC, area under the curve; BMI, body mass index (in the treated group, before starting the treatment); COH, controlled ovarian hyperstimulation (GnRH agonist, rFSH, hCG); E2, estradiol; FA, folic acid; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; IRI, immune reactive insulin; IVF, in vitro fertilization; HDL, high-density lipoprotein; HOMA, homeostatic model assessment; LA, lipoic acid; LDL, low-density lipoprotein; LH, luteinizing hormone; NA, not available; NAC, N-acetylcysteine; OCP, oral contraceptive pill (estradiol 30 μg/gestodene 75 μg); PRL, prolactin; RCT, randomized control trial; rFSH, recombinant follicle-stimulating hormone; SHBG, sex hormone binding globulin; T, testosterone.