Combination therapy of hypogonadism: the outcomes of Inokirol® administration in its composition

Introduction. Androgen deficiency in men is associated with multiple adverse effects on reproductive function and psychoemotional well‑being. Aromatase, the enzyme that catalyzes the conversion of androgens to estrogens and thereby maintains an appropriate sex‑steroid balance, represents a potential therapeutic target; the use of biologically active molecules with aromatase‑modulating properties may help restore the estradiol/testosterone (E2/T) ratio in men with functional hypogonadism. D‑chiro‑inositol is one such naturally occurring molecule that can modulate aromatase expression in a dose‑dependent manner and exerts insulin‑mimetic effects, reducing insulin resistance in adipose tissue. Importantly, modulation of aromatase expression by D‑chiro‑inositol does not result in complete enzyme blockade, thus avoiding adverse effects typically associated with aromatase inhibitors.

Objective. To evaluate the efficacy of D‑chiro‑inositol in the management of functional hypogonadism in men.

Materials and methods. A 90‑day, controlled study was conducted to assess the effect of the dietary supplement Inokirol®, containing D‑chiro‑inositol at aromatase‑modulating and insulin‑mimetic doses, on serum sex hormones and gonadotropins, biochemical parameters, and semen characteristics in 60 adult men with functional hypogonadism. Patients were randomized into two groups. Group 1 received 2,000 IU of vitamin D and 450 mg of omega‑3 polyunsaturated fatty acids (Detrimarin, 1 capsule daily) in combination with 1,200 mg of D‑chiro‑inositol (Inokirol®, 2 tablets daily). Group 2 received 2,000 IU of vitamin D and 450 mg of omega‑3 polyunsaturated fatty acids (Detrimarin, 1 capsule daily) plus a placebo visually indistinguishable from Inokirol®.

Results. In Group 1, supplementation with D‑chiro‑inositol (Inokirol®) led to a statistically significant increase in total testosterone by 33% (p < 0.00001) and an increase in the T/E2 ratio by 41% (p < 0.00001), accompanied by a marked improvement in sexual satisfaction. Estradiol concentrations remained stable, while the T/E2 ratio normalized. No statistically significant changes in these parameters were observed in Group 2. In Group 1, metabolic and lipid profile indices improved significantly, consistent with the insulin‑sensitizing action of D‑chiro‑inositol. Semen parameters improved in both groups; however, only in Group 1 was there an improvement in sperm motility and in the sperm DNA fragmentation index, suggesting the involvement of deeper mechanisms of spermatogenic regulation driven by changes in the intratesticular testosterone–estradiol balance.

Conclusion. Inokirol® use in men with functional hypogonadism resulted in a significant improvement in the T/E2 ratio at stable estradiol concentrations, indicating optimization of hormonal homeostasis through modulation of aromatase activity without suppression of pituitary regulation. In addition, D‑chiro‑inositol supplementation was associated with reduced insulin resistance and low‑density lipoprotein levels, as well as improved spermatogenesis, including a favorable effect on the sperm DNA fragmentation index.

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