Role of Myo-inositol and D-chiro Inositol on the Ovaric and Metabolic Functions

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age and is characterized by menstrual abnormalities, clinical or biochemical hyperandrogenism, multiple abnormal cysts and enlarge ovaries. Women affected by PCOS often suffer of insulin resistance and of a compensatory hyperinsulinemia which put them at risk of developing several metabolic disorders. Inositol is a six-carbon polyol which has been characterized as an insulin sensitizer: it exists as nine different isomers and among them myo-inositol and D-chiroinositol are the most represented and studied in physiology and physiopathology. In particular, myo-inositol (MI) and D-chiro inositol (DCI) glycans administration has been reported to exert beneficial effects at metabolic, hormonal and ovarian levels.

The aim of this randomized study is to evaluate the metabolic and ovaric effects of a six-month supplementation of myo-inositol and D-chiro-inositol on young women with PCOS and hyperinsulemia.

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Dietary supplement: Folic acid; Dietary supplement: Myo-inositol + D-chiro-inositol + Folic acid

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy
    • University of Pisa - Department of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• PCOS
• Women aged between 14-40 years
• BMI > 28
• Hyperinsulinemia

Exclusion Criteria:

• Pre-existing secondary endocrine and metabolic disorders
• Pre-existing secondary adrenal disorders
• Pharmacologic treatment in the last 3 months before entering the study
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Folic acid	Dietary supplement: Folic acid; Folic acid (200 mcg); 2 x die
Experimental: Inofolic Combi	Dietary supplement: Myo-inositol + D-chiro-inositol + Folic acid; Myo-inositol (550 mg) + D-chiro-inositol (13.8 mg) + Folic acid (200 mcg); 2 x die

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual cycle restoration		At 6 months
Score hirsutism (Ferriman-Gallwey classification)		At 6 months
Serum progesterone		At 6 months
Testosterone level test		At 6 months
Oral glucose tolerance test (OGTT)	Evaluation of glycemia and insulinemia levels	At 6 months
Homeostasis Model Assessment (HOMA-index)		At 6 months
Sex hormone binding globulin (SHBG) test		At 6 months
Androstenediol level test		At 6 months
Androstenedione level test		At 6 months
Free Androgen Index (FAI) level test		At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)		At 6 months
Change from baseline in diastolic blood pressure levels		At 6 months
Change from baseline in systolic blood pressure levels		At 6 months
Number of patients with abnormal ovarian size and morphology	Ovarian ultrasound scan for the assessment of size and morphology	At 6 months
Luteinizing Hormone (LH) level test	Analysis of LH levels should be performed between the 7th and the 10th day of the cycle	At 6 months
Follicle Stimulating Hormone (FSH) level test	Analysis of FSH levels should be performed between the 7th and the 10th day of the cycle	At 6 months
Estradiol (E2) level test	Analysis of E2 levels should be performed between the 7th and the 10th day of the cycle	At 6 months

Collaborators and Investigators

• Sponsor: Lo.Li.Pharma s.r.l

Publications and helpful links

General Publications

• Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006-11. doi: 10.1210/jcem.84.11.6148.
• Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72. doi: 10.1210/jcem.84.10.6079.
• Legro RS, Castracane VD, Kauffman RP. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv. 2004 Feb;59(2):141-54. doi: 10.1097/01.OGX.0000109523.25076.E2.
• Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol. 1997 May;15(2):111-22. doi: 10.1055/s-2007-1016294.
• 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 Jun;23(6):1439-46. doi: 10.1093/humrep/den097. Epub 2008 Mar 29.
• 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 Apr 29;340(17):1314-20. doi: 10.1056/NEJM199904293401703.
• 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 Jun;17(6):1591-6. doi: 10.1093/humrep/17.6.1591.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 15, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (Estimate): June 22, 2012

Study Record Updates

• Last Update Posted (Actual): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: PCOS; Metabolic disorders; D-chiro-inositol; Ovarian functionality; Myo-inositol
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex; Inositol
• Other Study ID Numbers: MI-DCI