Inositols in the ovaries: activities and potential therapeutic applications

ABSTRACT

Introduction

Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones.

Areas covered

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. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility.

Expert opinion

Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients’ specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.

KEYWORDS:

• Myo-inositol
• d-chiro-inositol
• Polycystic Ovary Syndrome
• Ovarian Steroidogenesis
• Epimerase
• Insulin Resistance

Article highlights

• Physiological content of myo-inositol (MI) and d-chiro-inositol (DCI) is specific of each tissue or organ, with the individual insulin response that regulates the local MI-to-DCI ratio. In case of hyperinsulinemia, tissues that do not develop insulin resistance, like the ovaries, become enriched in DCI.

• Inositols participate in the steroidogenesis, as they are second messengers of insulin and gonadotropins. Moreover, recent evidence suggested that DCI downregulates the expression of aromatase, reducing the conversion of androgens into estrogens.

• MI is currently used to treat infertility and menstrual irregularities in polycystic ovary syndrome (PCOS). Combination of MI and DCI in the 40:1 ratio appears to be the best option to improve the metabolic profile in overweight PCOS subjects. Treatment with DCI should be carefully evaluated in order to avoid the onset of unwanted side effects that may worsen PCOS symptoms.

• Elevated MI-to-DCI ratios in the follicular fluid are associated with good-quality blastocysts, supporting MI supplementation before assisted reproduction technology. Moreover, MI treatment during ovarian stimulation increases FSH sensitivity, reducing the total amount of gonadotropins required in the stimulation protocols.

• Reduced absorption of inositols may reduce the efficacy of the treatment. Alpha-lactalbumin modulates the opening of intestinal tight junctions, enhancing the absorption of MI and DCI even in ‘inositol-resistant’ subjects.

Declaration of interest

G Forte and V Unfer are employees at Lo.Li. Pharma s.r.l. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.