Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients

  title={Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients},
  author={Giovanni Monastra and Vittorio Unfer and Abdel Halim Harrath and Mariano Bizzarri},
  journal={Gynecological Endocrinology},
  pages={1 - 9}
Abstract Polycystic ovary syndrome (PCOS), a relevant cause of infertility, is a heterogeneous, endocrine disorder affecting up to 10–15% of women in reproductive age. Besides hyperandrogenism, insulin resistance (IR) plays a key role in such syndrome. Insulin-sensitizing drugs, such as Metformin, are effective in treating hyper-insulinemic PCOS patients. Recently, inositols – myo-inositol (MI) and D-chiro-inositol (DCI) – have shown to be an efficient and safe alternative in PCOS management… 

The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios.

The data demonstrated that DCI activity is beneficial mainly at a specific ratio with MI, whereas the increase of DCI causes the loss of the beneficial effects at reproductive level, which validate a previous preclinical study with different MI/DCI ratios carried out in an experimental model of PCOS mice.

Inositols: From Established Knowledge to Novel Approaches

The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis, and proposes two different aims: restoring the inositol physiological ratio and altering the ratio in a controlled way to achieve specific effects.

Inositols in Polycystic Ovary Syndrome: An Overview on the Advances

Altered Ovarian Inositol Ratios May Account for Pathological Steroidogenesis in PCOS

The literature that supports the connection between altered MI/DCI ratios and pathological steroidogenesis observed in PCOS women is reviewed, and the application of inositol-based treatment protocols in managing PCOS symptoms and improving the quality of patients’ life is discussed.

Metabolic Effects of D-Chiro-Inositol and Myo-Inositol in Polycystic Ovary Syndrome

The objective is to evaluate the effect of DCI combined with myo-inositol (MI), and metformin on the metabolic outcomes of PCOS in a Lebanese women cohort.

Inositols in the ovaries: activities and potential therapeutic applications

This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis.

An innovative approach to polycystic ovary syndrome

The main stages of Vittorio Unfer’s scientific career have been closely intertwined with important phases of the recent pharmacological research about the topic and his researches allowed to identify “the D-Chiro-Inositol Paradox in the Ovary” and the best myo- inositol/D-chiro-inositol ratio (40:1) for the treatment of PCOS.

D-Chiro-Inositol Treatment Affects Oocyte and Embryo Quality and Improves Glucose Intolerance in Both Aged Mice and Mouse Models of Polycystic Ovarian Syndrome

The results indicate that D-Chiro-inositol works in preclinical models of PCOS and offer insight into its mechanism of action when used to treat this infertility-associated syndrome.

Inositol Treatment for PCOS Should Be Science-Based and Not Arbitrary

It is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol's efficacy.

The use of inositol(s) isomers in the management of polycystic ovary syndrome: a comprehensive review

  • A. GatevaV. UnferZ. Kamenov
  • Biology
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2018
Myo-inositol monotherapy results more effective in preventing and treating GDM even if a larger cohort of studies is needed to better clarify these results.



The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone.

The combined administration of MI and DCI in physiological plasma ratio (40:1) should be considered as the first line approach in PCOS overweight patients, being able to reduce the metabolic and clinical alteration of PCOS and, therefore, reduce the risk of metabolic syndrome.

Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome.

In obese women with PCOS, metformin may improve the action of insulin in part by improving insulin-mediated release of DCI-IPG mediators, as evidenced by increased bioactive DCI/AUC released per unit of insulin.

Reflections on inositol(s) for PCOS therapy: steps toward success

  • J. NestlerV. Unfer
  • Biology
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2015
The “DCI paradox” hypothesis suggests that in the ovary of PCOS women, an increased epimerase activity leads to a DCI overproduction and MI depletion, which could be the cause of the poor oocyte quality and the impairment in the FSH signaling.

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials

An overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS is provided.

Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome.

D-chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.

d-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review

  • N. GalazisM. GalaziW. Atiomo
  • Medicine
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2011
Heterogeneity observed in the methodologies of each study, the scarcity of relevant studies and the small sample sizes used prohibit reliable conclusions to be drawn, therefore, more studies must be conducted in the future to evaluate accurately the effects of DCI in PCOS.

Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome.

The coupling between insulin action and the release of the DCI-IPG mediator is selectively impaired in obese PCOS women, which may contribute to the insulin resistance in these women.

Does myo-inositol effect on PCOS follicles involve cytoskeleton regulation?

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome

Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion and insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index.

The Ratio of MI to DCI and Its Impact in the Treatment of Polycystic Ovary Syndrome: Experimental and Literature Evidences

Although MI and DCI fulfill different roles, often their biological activities are confused and at ovarian level, MI plays a pivotal role in the FSH signaling while DCI promotes insulin-dependent androgen synthesis.