Authors’ reply to: “Empiric” inositol supplementation in normal-weight non-insulin resistant women with polycystic ovarian disease: from the absence of benefit to the potential adverse effects

Abstract

Ó Springer-Verlag Berlin Heidelberg 2015 Dear Editor, We appreciate Vitagliano and Colleagues' interest in our recent article [1] about ovarian function and metabolic factors in women affected by polycystic ovary syndrome (PCOS) after treatment with D-chiro-inositol. We are grateful for their insightful comments [2] and the opportunity to clarify a number of elements from our work. As evidenced by Vitagliano et al., despite the plethora of published papers about the treatment of PCOS with Inositol isoforms (for systematic reviews, see Unfer et al. [3] and Galazis et al. [4]), very few of them focused on lean patients (BMI \ 25).Accumulating evidence suggests that pre-treatment BMI may play a key role in the effect of inositol treatment of PCOS: Genazzani et al. [5] recently showed D-chiroinositol administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives. In our previous study [1], even if all the recruited patients were lean, we reported 5.38 ± 1.54 as mean glycaemia/IRI ratio and 3.44 ± 1.18 as mean HOMA (Homeostasis Model Assessment) index, so we evidenced insulin resistance/hyperglycaemia (HOMA C 2.5) in the enrolled population. Moreover, none of these patients had diabetic relatives (first or second degree).In this context, it was recently evidenced [6] that even in the absence of insulin resistance, the rate of anovulation in PCOS remains still high. As interestingly suggested by Vitagliano's group, the percentage of poor responder in our study could depend (at least in part) by a subgroup of noninsulin resistant lean PCOS patients.Moreover, some authors [7] found no change in D-chiroinositol-containing inositolphosphoglycan (DCI-IPG) release, suggesting that impaired DCI-IPG release in these women may have represented a functional defect (e.g., intracellular defect in formation or release of the DCI-IPG mediator) rather than a simple nutritional deficiency in the substrate D-chiro-inositol. Nevertheless, also this study is strongly conditioned by very small samples (just 6 patients in the D-chiro-inositol group and 5 in the placebo group) and it is unclear why the authors choose to administrate 1200 mg of the study drug.Vitagliano's hypothesis, even it has to be confirmed by future studies, could explain also why some other authors [8] found that very (unnecessary?) high dosages (1200-2400 mg daily) of D-chiro-inositol may worse oocyte quality and ovarian response in PCOS patients without insulin resistance and/or hyperglycaemia after induction of ovulation.We previously evidenced [9, 10] that both the isoforms of inositol were effective in improving ovarian function and metabolism in patients with PCOS, although myoinositol showed the most marked effect on the metabolic profile, whereas D-chiro-inositol reduced hyperandrogenism better. This conflicting results could depend on the different selection of the patients (Isabella and Raffone [8] selecte...

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