M. Nordio, M. Espinola, G. Bilotta, E. Capoccia, M. Oliva

Recent studies reported possible concerns following long-lasting treatments
with high doses of D-chiro-inositol in women. However, to date, no clinical trial has investigated or
validated these concerns. We addressed this issue both retrospectively and with a prospective pilot
study. Methods: For the retrospective analysis, we searched our databases for insulin-resistant
women who took 1200 mg/day D-chiro-inositol for 6 months. In our prospective study, we enrolled
10 healthy women to supplement with the same therapeutic scheme. We performed statistical analyses
through the Wilcoxon Signed-Rank Test. A p-value < 0.05 was considered significant. Results:
Twenty women underwent 6 months of 1200 mg/day D-chiro-inositol. The treatment significantly
decreased BMI, glycemia, insulinemia, HOMA-IR, serum levels of LH, total testosterone, and
DHEAS. Serum estradiol rose and menstrual abnormalities occurred following the treatment. In our
prospective study, we observed increases in serum levels of total testosterone and asprosin in
healthy women. Conclusions: This is the first clinical evidence demonstrating that long-term treatments
with high dosages of D-chiro-inositol can predispose women to hormonal and menstrual
abnormalities. Moreover, the accumulation of D-chiro-inositol following such treatment regimen
may lead to detrimental effects in non-reproductive tissues, as demonstrated by the increase in
asprosin levels.