Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols.

Antonio Simone Laganà,Onofrio Triolo,Rosita Angela Condorelli,Sandro La Vignera,Paola Rossetti,Giuseppe Gullo,Roberta Granese,Massimo Buscema

doi:10.1155/2016/6306410

Abstract

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are 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. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

Highlights

Antonio Simone Laganà,1 Paola Rossetti,2 Massimo Buscema,2 Sandro La Vignera,3 Rosita Angela Condorelli,3 Giuseppe Gullo,1 Roberta Granese,1 and Onofrio Triolo1
The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with Polycystic ovary syndrome (PCOS)
PCOS often develops during puberty inducing dermatological signs, irregular menses, and biochemical alterations associated with high levels of testosterone, DHEA, androstenedione, and luteinizing hormone (LH) and increased LH/follicle-stimulating hormone (FSH) ratio, together with a concurrent reduction of sex hormone binding globulin (SHBG) and insulin-like growth factor (IGF) binding protein [32]

Summary

PCOS and Metabolic Aspects

Insulin-resistance and hyperinsulinemia are tightly related to pathogenesis of PCOS [12, 13] which may be exacerbated by coexistence of obesity, affecting about 50% of women with PCOS [14]. The prevalence of MS in patients with PCOS seems to be 2-fold higher than reported for agematched general population even when stratified by both age and Body Mass Index (BMI). Other authors [21] found a higher risk of MS in young patients with PCOS compared with general age-matched population such as 37% versus 5% and 47 versus 13%, according to two different criteria proposed for diagnosis of MS [22, 23]; among obese young patients the prevalence increased to 63%. A pioneering study by Burghen et al [12] identified a relationship between hyperandrogenism and hyperinsulinemia in polycystic ovary disease Since those first studies it became evident that insulin-mediated glucose disposal, calculated with euglycemic glucose clamp, was decreased in PCOS as a result of insulin-resistance in skeletal muscle and fat tissue. Other studies confirmed a decrease in both first and second phases of insulin response to glucose, suggesting abnormal β-cell function, in women with PCOS and abnormal glucose tolerance [17]

PCOS and Impaired Follicular Maturation

Rationale of Inositol-Based Therapeutic

Clinical Data

Findings

Conclusion