Metformin vs Myoinositol: Which Is Better in Obese Polycystic Ovary Syndrome Patients?

A Randomized Controlled Crossover Study

Valeria Tagliaferri; Daniela Romualdi; Valentina Immediata; Simona De Cicco; Christian Di Florio; Antonio Lanzone; Maurizio Guido


Clin Endocrinol. 2017;86(5):725-730. 

In This Article

Abstract and Introduction


Context Due to the central role of metabolic abnormalities in the pathophysiology of polycystic ovary syndrome (PCOS), insulin sensitizing agents have been proposed as a feasible treatment option.

Objective To investigate which is the more effective between metformin and myoinositol (MYO) on hormonal, clinical and metabolic parameters in obese patients with PCOS.

Study design Crossover randomized controlled study.

Patients Thirty-four PCOS obese women (age: 25·62 ± 4·7 years; BMI: 32·55 ± 5·67 kg/m2) were randomized to receive metformin (850 mg twice a day) or MYO (1000 mg twice a day) for 6 months. After a 3 month washout, the same subjects received the other compound for the following 6 months.

Measurements Ultrasonographic pelvic examinations, hirsutism score, anthropometric and menstrual pattern evaluation, hormonal profile assays, oral glucose tolerance test (OGTT) and lipid profile at baseline and after 6 months of treatment were performed.

Results Both metformin and MYO significantly reduced the insulin response to OGTT and improved insulin sensitivity. Metformin significantly decreased body weight and improved menstrual pattern and Ferriman–Gallwey score. Metformin treatment was also associated with a significant decrease in LH and oestradiol levels, androgens and anti-müllerian hormone levels. None of these clinical and hormonal changes were observed during MYO administration.

Conclusions Both treatments improved the glyco-insulinaemic features of obese PCOS patients, but only metformin seems to exert a beneficial effect on the endocrine and clinical features of the syndrome.


During the past decades, increasing evidence has supported the central role of metabolic disturbances such as insulin resistance and/or compensatory hyperinsulinaemia in the pathogenesis of polycystic ovary syndrome (PCOS).[1] This endocrine disorder affects approximately 5–10% of women of reproductive age and is characterized by the heterogeneous combination of menstrual irregularities, chronic anovulation, hyperandrogenism and metabolic abnormalities.[2]

Hyperinsulinaemia seems to directly stimulate both ovarian and adrenal androgen secretion and to suppress liver sex hormone-binding globulin (SHBG) synthesis causing an increase in free, biologically active androgens. The excess in androgen production, worsened by hyperinsulinaemia, causes premature follicular atresia and anovulation. Moreover, at the central level, insulin seems to be involved in the dysregulation of LH secretion.[3]

Based on this rationale, insulin-sensitizing agents have been proposed as a useful primary or adjunctive treatment to improve clinical and biochemical parameters in patients with PCOS by lowering insulin secretion. In this group of compounds, the biguanide metformin has been the most extensively investigated: in randomized trials, it was reported to improve insulin sensitivity, body mass index (BMI), menstrual irregularities and hyperandrogenism in most PCOS women.[4]

Despite the clinical efficacy, the metformin administration is burdened by several side effects, such as nausea, vomiting and gastrointestinal discomfort[5,6] in about 30% of users, accounting for the poor compliance associated with this treatment.

Several reports in literature have also analyzed the role of thiazolidinediones in PCOS treatment.[7,8] These drugs are able to restore normal menstrual cyclicity and improve clinical signs of hyperandrogenism: nonetheless, the widespread use of these substances is restricted by their documented hepatotoxicity.[4]

Recently, attention has been given to the role of inositol–phosphoglycan (IPG) mediators in insulin action. Molecular and animal studies showed that D-chiro-inositol deficiency and an imbalance with its precursor myoinositol (MYO) are directly related to the insulin resistance.[9] In particular, the stereoisomer MYO is an important constituent of the follicular microenvironment, where it seems to play an important role in both nuclear and cytoplasmic oocyte development. It was demonstrated that in human follicular fluids, higher concentrations of MYO are related to a better quality of oocytes.[10]

Some authors have experimented with MYO supplementation in both obese and lean PCOS patients, reporting varying degrees of improvement in clinical, hormonal and metabolic features of the syndrome. However, previous reports in PCOS subjects exclusively evaluated the clinical effects of formulations containing MYO plus folic acid.[11] In addition, no direct comparisons with other insulin sensitizing compounds, regarding the effects on clinical and biochemical characteristics of the syndrome, are available in literature. The only published study comparing MYO and metformin focused on the ovulation and pregnancy rates in a population of infertile PCOS women.[12]

Based on these evidences, in the present crossover study, we aimed at comparing for the first time the two insulin sensitizing agents metformin and MYO in terms of efficacy in the treatment of overweight, obese PCOS patients.