Comment on “Inositols: from physiology to rational therapy in gynecological clinical practice”

Dear Editor,

We read with great interest the article by Unfer et al. [1], which focused on the inositol isoforms’ physiological role in glycemic and hormonal homeostasis and their possible rationale in gynecological practice, with particular attention on the polycystic ovary syndrome (PCOS) therapy. Indeed, we appreciated the clarity of the reported information, which leads the readers to have a complete overview of the topic and guide them to an evidence-based use of both inositol isoforms. In this view, we take the opportunity to stress several points which would let us further realize the mechanisms behind inositol’s pleiotropic actions in PCOS. Although it is widely accepted that insulin resistance and compensatory hyperinsulinemia play an important pathogenic role in the hyperandrogenism and anovulation of women affected by PCOS, accumulating evidence [2] suggests that this syndrome could be considered as the result of concurrent endocrinological alterations: first of all obesity, which often correlates with PCOS, seems to play a key role in increasing circulating androgens; high levels of luteinizing hormone (LH), reactive species of oxygen and pro-inflammatory cytokines within the ovary, typical of PCOS patients, could inhibit of the physiological process of ovarian follicular maturation; finally, hyperandrogenism acts synergistically with LH to enhance androgen production of theca cells and reduces circulating sex hormone binding globulin, which in turn increases the level of free testosterone. Regarding metabolic profile, we recently suggested [3] that D-Chiro-Inositol (DCI) and Myo-Inositol (MI) metabolic derivatives work in synergy with each other: MI induces glucose transporter type 4 translocation to the cell membrane, thus enhancing cellular uptake of glucose; DCI stimulates pyruvate dehydrogenase, thus supporting adenosine triphosphate production through the Krebs’ cycle; both MI and DCI stimulate glycogen synthase, thus supporting glucose conversion to glycogen stored inside cells; finally, MI derivatives inhibits adenylate cyclase enzyme, which controls free fatty acid release. Reflecting these elements on the clinical management, we recently showed MI beneficial effects on semen parameters before in vitro fertilization [4] and that both the isoforms of inositol and combined therapy were effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better [2]. Although Unfer et al. [1] proposed MI:DCI ratio of 40:1 as the most appropriate, we solicit further studies to establish the best therapeutic strategies based on patient’s clinical condition, also in combination with other nutraceuticals [5].

Declaration of interest

The authors 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.

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Funding

This paper was not funded.