New clinical targets of d-chiro-inositol: rationale and potential applications

ABSTRACT

Introduction

Inositols have a key role in ovarian physiology and the literature reports a wealth of studies about the major isomer, myo-inositol (MI). However, information about d-chiro-inositol (DCI) is still scarce, despite the ratio MI:DCI is tissue-specific and actively maintained by an insulin-dependent epimerase enzyme.

Areas covered

This expert opinion provides an overview of the physiological contribution of DCI in regulating steroidogenesis. DCI indeed mediates the intracellular signaling of insulin, which induces the biosynthesis of androgens. Studies on second messengers of insulin also revealed that DCI has a specific role in modulating the activity of aromatase enzyme. Specifically, recent findings demonstrated that DCI influences the enzyme gene expression, thus reducing the conversion of androgens into estrogens.

Expert opinion

Available evidence suggests that the effects of DCI administration may be similar to those of aromatase inhibitors, but without causing hypo-estrogenic states. Therefore, DCI treatments should be evaluated for either estrogen-dependent gynecological conditions or low testosterone states in male subjects.

KEYWORDS:

• D-chiro-inositol
• aromatase
• estrogen
• endometriosis
• controlled ovarian hyperstimulation
• male hypogonadism

Article highlights

• d-chiro-inositol (DCI), besides being a second messenger of insulin, regulates female steroidogenesis by enhancing testosterone biosynthesis and downregulating the expression of aromatase.

• As second messenger of insulin, short-term administration of DCI may reduce androgen levels in insulin-resistant women; extended treatments result in androgen increase due to the activity on aromatase and on testosterone biosynthesis.

• Taking into account the modulatory action on aromatase, DCI may find application for estrogen-dependent gynecological diseases characterized by increased expression of the enzyme.

• Tailoring the dosage and the duration of the intervention, DCI treatment may represent an appealing therapeutic approach for increasing the androgen-to-estrogen ratio in men with late-onset hypogonadism.

This box summarizes key points contained in the article.

Declaration of interest

V. Unfer is an employee at Lo.Li Pharma s.r.l., Rome, Italy. The other authors (A.S. Laganà and S. Garzon) have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded