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

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, as both inositol isoforms are able to counteract downstream consequences of insulin resistance. Yet, whereas DCI contributes in mediating insulin activity mainly on non-ovarian tissues, MI displays specific effects on ovary, chiefly by modulating glucose metabolism and FSH-signaling. Moreover, MI may also improve ovarian functions by modulating steroid metabolism through non-insulin-dependent pathways. As DCI and MI activity likely involves different biological mechanisms, both inositol isoforms can be synergistically integrated according to a multitargeted design, by combining MI and DCI in a ratio corresponding to their physiological plasma relative amount (40:1). New experimental and clinical evidence with MI plus DCI evidenced the suitability of such integrated approach, and provided promising results. Further studies need to investigate thoroughly the molecular mechanism and confirm such preliminary data.

Chinese abstract

多囊卵巢综合征 (PCOS) 是与不孕相关的多因素导致的内分泌紊乱, 在生育年龄女性中达到10-15%。除了雄激素过多症, 胰岛素抵抗发挥了关键作用。胰岛素增敏药物, 例如二甲双胍对治疗高胰岛素血症的PCOS患者是有效的。最近显示肌醇 (inositols – myoinositol, MI) 和D-手性肌醇 (D-chiro-inositol, DCI) 作为PCOS管理的另一种选择是安全有效的。肌醇的两个亚型能够抵消胰岛素抵抗的下游作用。然而, DCI调节胰岛素活性主要不是通过卵巢组织, MI通过调节糖代谢和卵泡刺激素信号途径, 对卵巢产生特殊的效应。此外, MI也可以通过非胰岛素依赖的途径利用调节类固醇代谢改善卵巢功能。DCI和MI活性可能包括不同的生物学机制, 两个肌醇亚型能够按照多靶向设计以协同方式整合, 通过把MI和DCI按照符合它们生理学上血浆相对含量的比例 (40:1) 联合。新的MI加上DCI方案的实验室和临床证据显示:这样的整合方案是合适的, 并提供了有前景的结果。我们更需要深入研究分子机制并确认前期的数据。

• D-chiro-inositol
• hyperandrogenism
• insulin resistance
• metformin
• myo-inositol
• polycystic ovary syndrome
• sialylated FSH

Declaration of interest

Vittorio Unfer is an employee at Lo.Li.Pharma, Rome, Italy. Giovanni Monastra, Abdel Halim Harrath and Mariano Bizzarri declare that there is no conflict of interest regarding the publication of this paper.

Abdel Halim Harrath and Mariano Bizzarri would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this Research group NO.(RG#164).