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

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.

Association between Insulin Resistance and Cardiovascular Risk Factors in Polycystic Ovary Syndrome Patients

“…1 In addition to being an ovulatory disorder, PCOS can also be considered a metabolic disorder, since insulin resistance (IR) and consequent compensatory hyperinsulinemia, which are closely related to its pathogenicity and comorbidities, can be exacerbated by the coexistence of obesity, which affects $ 50% of PCOS women. 2 However, IR is not part of the diagnostics criteria, partly and probably because of the absence of an accurate validated method for use in clinical practice, since the hyperinsulinemic-euglycemic clamp, the gold standard for diagnosing IR, is expensive and difficult to perform. 3 It has been observed that, in addition to IR, PCOS patients are at a higher risk of developing glucose intolerance, Type 2…”

“…Diabetes Mellitus, dyslipidemia, and metabolic syndrome (MS), 1,2 all of which are traditional risk factors for the development of cardiovascular diseases (CVDs).…”

Comment on “Inositols: from physiology to rational therapy in gynecological clinical practice”

“…In this view, we take the opportunity to stress several points which would let us further realize the mechanisms behind inositol's pleiotropic actions in PCOS. Although it is widely accepted that insulin resistance and compensatory hyperinsulinemia play an important pathogenic role in the hyperandrogenism and anovulation of women affected by PCOS, accumulating evidence [2] suggests that this syndrome could be considered as the result of concurrent endocrinological alterations: first of all obesity, which often correlates with PCOS, seems to play a key role in increasing circulating androgens; high levels of luteinizing hormone (LH), reactive species of oxygen and proinflammatory cytokines within the ovary, typical of PCOS patients, could inhibit of the physiological process of ovarian follicular maturation; finally, hyperandrogenism acts synergistically with LH to enhance androgen production of theca cells and reduces circulating sex hormone binding globulin, which in turn increases the level of free testosterone. Regarding metabolic profile, we recently suggested [3] that D-Chiro-Inositol (DCI) and MyoInositol (MI) metabolic derivatives work in synergy with each other: MI induces glucose transporter type 4 translocation to the cell membrane, thus enhancing cellular uptake of glucose; DCI stimulates pyruvate dehydrogenase, thus supporting adenosine triphosphate production through the Krebs' cycle; both MI and DCI stimulate glycogen synthase, thus supporting glucose conversion to glycogen stored inside cells; finally, MI derivatives inhibits adenylate cyclase enzyme, which controls free fatty acid release.…”

“…Regarding metabolic profile, we recently suggested [3] that D-Chiro-Inositol (DCI) and MyoInositol (MI) metabolic derivatives work in synergy with each other: MI induces glucose transporter type 4 translocation to the cell membrane, thus enhancing cellular uptake of glucose; DCI stimulates pyruvate dehydrogenase, thus supporting adenosine triphosphate production through the Krebs' cycle; both MI and DCI stimulate glycogen synthase, thus supporting glucose conversion to glycogen stored inside cells; finally, MI derivatives inhibits adenylate cyclase enzyme, which controls free fatty acid release. Reflecting these elements on the clinical management, we recently showed MI beneficial effects on semen parameters before in vitro fertilization [4] and that both the isoforms of inositol and combined therapy were 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 [2]. Although Unfer et al [1] proposed MI:DCI ratio of 40:1 as the most appropriate, we solicit further studies to establish the best therapeutic strategies based on patient's clinical condition, also in combination with other nutraceuticals [5].…”

Insulin Resistance and Its Associated Risk Factors in Nigerian Women with Polycystic Ovary Syndrome

“…However, one condition that correlates closely with the pathogenesis of PCOS is insulin resistance, which is present in 50% -75% of women with PCOS [3]. Insulin resistance and subsequent compensatory hyperinsulinemia which are closely related to the pathogenicity and co-morbidities of PCOS can be exacerbated by the coexistence of obesity which affects approximately 50% of PCOS women [4]. The prevalence rates of IR reported among US women with PCOS range from 44% to 70% [3] which are significantly higher than the rates reported among Iranian, Thai, and Vietnamese PCOS women [5] [6] [7].…”