Myo-inositol Versus D-chiro-inositol in the Treatment of Polycystic Ovary Syndrome and Insulin Resistance: Evaluation of Clinical, Metabolic, Endocrine and Ultrasound Parameters

Insulin resistance has important implications in the pathogenesis of the polycystic ovary syndrome (PCOS) and insulin-sensitizing drugs are considered a useful therapeutic approach.

Reduction of insulin levels with administration of insulin sensitizing agents has been found to be beneficial in lowering both hyperinsulinemia, hyperandrogenemia, and restoring ovulation. Metformin alone or in combination with oral contraceptives (OCs) has been widely used in the long term treatment of women with PCOS in whom it modifies the ovarian morphology, improves intraovarian androgen levels, and enhances systemic and local insulin resistance. Despite to these beneficial effects, several side effects have been reported due to the long term administration of this drug.

In the recent years, inositol has found more and more space in the reproductive clinical practice. Indeed, inositol have been classified as "insulin sensitizing agent" and it is mainly used as a chronic treatment for PCOS. Inositol exists in 9 different isomers and in particular several studies on Myo-inositol and D-chiro-inositol were reported.

In this study myo-inositol versus D-chiro-inositol treatments were compared to placebo in women with PCOS and with or without insulin resistance.

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Dietary supplement: Myo-inositol + Folic acid; Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; Drug: Folic acid, vit B12

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Catania, Italy
    • Istituto di Patologia Ostetrica e Ginecologica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women fulfilled two out of three diagnostic criteria for PCOS

Exclusion Criteria:

• Women with pre-existing secondary endocrine disorders
• Women with personal history of hypertension, diabetes mellitus or cardiovascular disorders
• Women who received treatment with other drugs for the previous 6 months before entering the study.

Study Plan

How is the study designed?

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Insulin resistant patients	Dietary supplement: Myo-inositol + Folic acid; Myo-inositol (2g) Folic acid (200mcg) (2 per day); Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; D-Chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day); Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; D-chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day); Drug: Folic acid, vit B12; Folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)
Other: Non-insulin resistant patients	Dietary supplement: Myo-inositol + Folic acid; Myo-inositol (2g) Folic acid (200mcg) (2 per day); Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; D-Chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day); Dietary supplement: D-chiro-inositol, manganese, folic acid, vit B12; D-chiro-inositol (500 mg), manganese (1 mg), folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day); Drug: Folic acid, vit B12; Folic acid (200 mcg), vit B12 (1.25 mcg) (2 per day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Body Mass Index (BMI)
Menstrual cycle
Score acne (acne grading system by Cremoncini et al)
Score hirsutism (Ferriman-Gallwey score)
Alopecia
Oral Glucose Tolerance Test (OGTT)
Glucagon levels
C-peptide test
Myo-inositol serum concentration
D-chiro-inositol serum concentration
Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), and Estradiol (E2) levels test
Prolactin (PRL) levels test
Thyroid-stimulating hormone (TSH), free thyroid hormone (fT3 and fT4), and alpha-1 antitrypsin (AAT) test
Total and free testosterone levels
Sex hormone binding globulin (SHBG) test
17-Hydroxyprogesterone (17-OHP) levels
Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) levels
delta 4-androstenedione levels
progesterone levels
Adrenocorticotropic Hormone (ACTH) stimulation test
Ovarian size and morphology	Ovarian ultrasound scan for the assessment of size and morphology
Antral follicle counts
Stromal/Cortical ratio in the ovary
Endometrial thickness	Transvaginal ultrasound measurement of endometrial thickness performed between day 3 and 5 of the menstrual cycle.

Collaborators and Investigators

• Sponsor: AGUNCO Obstetrics and Gynecology Centre

Publications and helpful links

General Publications

• Larner J, Brautigan DL, Thorner MO. D-chiro-inositol glycans in insulin signaling and insulin resistance. Mol Med. 2010 Nov-Dec;16(11-12):543-52. doi: 10.2119/molmed.2010.00107. Epub 2010 Aug 27.
• Costantino D, Minozzi G, 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 Mar-Apr;13(2):105-10.
• 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 Apr;26(4):275-80. doi: 10.3109/09513590903366996.
• Larner J. D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47-60. doi: 10.1080/15604280212528.

Study record dates

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (Estimate): January 23, 2012

Study Record Updates

• Last Update Posted (Estimate): January 23, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Insulin resistance; PCOS; D-chiro-inositol; Myo-inositol
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Physiological Effects of Drugs; Trace Elements; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; Inositol; Manganese
• Other Study ID Numbers: MIvsDCI_PCOS/IR