On the Therapy for Polycystic Ovary Syndrome.

Sir,

We have read with great attention the article titled, “The inositols and polycystic ovary syndrome” by Kalra et al.[1] The authors have correctly outlined the physiological activities of the two most important stereoisomers of inositol, myoinositol (MI), and D-chiro-inositol (DCI). We provide a more accurate analysis of these data, which will help ensure pragmatic prescription of these useful molecules.

Kalra et al. stated, “the correction of systemic insulin resistance by MI will treat the metabolic features of polycystic ovary syndrome (PCOS). Simultaneously, adequate DCI levels will create a healthy intraovarian milieu, which will correct hyperandrogenism, improve menstrual regularity, and promote ovulation and fertility. …While MI is necessary for metabolic management, DCI is equally important for menstrual, ovulatory, and cutaneous hyperandrogenic resolution. …A high concentration of DCI is necessary to circumvent epimerase deficiency and ensure adequate levels in the ovary. Most pharmaceutical preparations provide very low amounts of DCI which are insufficient to achieve adequate levels in the ovary. Hence, formulations with relatively higher levels of DCI are preferred.”

Recent scientific data, however, suggest otherwise.[23] Of the two stereoisomers, MI stands out for its important biological roles as a leading molecule, whereas different integrative functions are carried out by DCI. In particular, whereas the activation of glucose transporters and glucose utilization take place under the regulation of MI, glycogen synthesis is mainly controlled through DCI. On the other hand, in the ovary, MI regulates glucose uptake and follicle-stimulating hormone (FSH) signaling, while DCI modulates insulin-induced androgen synthesis.[23] In physiological conditions, the intracellular pool of inositol in human ovaries contains 99% of MI, whereas the remaining part is DCI.[4] In the ovary of PCOS women, we find an imbalance between MI and DCI concentrations, with a putative MI deficiency, which might impair the FSH signaling.[4] In these conditions, glucose uptake and metabolism of both oocytes and follicular cells are negatively affected compromising oocyte quality that depends on MI levels.[3] The improvement of ovarian function, as well as hormonal and metabolic parameters, was demonstrated after MI treatment in PCOS women.[5] Moreover, comparing the effects of metformin and MI on restored spontaneous ovulation activity in PCOS patients, the treated group showed better results for healed patients' number and recovery time.[3] Finally, high doses of DCI alone, administered to PCOS subjects, were found significantly detrimental for oocytes and therefore for fertility.[3]

Last but not least, MI is a well-established safe molecule,[6] whereas the data are lacking for DCI. In conclusion, therapeutically, DCI plays a relevant function at systemic, and not local, level in the metabolic syndromes, where its administration can improve insulin sensitivity and reduce serum free testosterone levels compared to placebo group. However, at elevated doses, it is harmful in PCOS patients. On the other hand, MI exerts positive effects both at systemic and local (ovary) level.

Financial support and sponsorship

Nil.

Conflicts of interest

Vittorio Unfer is an employee at Lo. Li. Pharma, Rome, Italy.