A PCOS Paradox: Does Inositol Therapy Find a Rationale in All the Different Phenotypes?

Abstract

A recent evaluation of the published data regarding the PCOS topic has highlighted a paradox in the definition of this condition. Even though the name of the syndrome refers to ovarian dysfunction, it seems that patients diagnosed with PCOS are more likely affected by an endocrine and metabolic issue. The term PCOS might not be appropriate to indicate the phenotypes described by the Rotterdam criteria, since the only phenotype with a gynecological issue alone is PCOS phenotype D. This novel perspective regarding how PCOS is currently defined leads the way to a reinterpretation of the entire pathological context and the treatment prescribed, such as inositols. A new point of view on the etiopathogenesis of the disease completely changes the current meaning of PCOS and consequently the therapeutic rationale evaluated to date.

Androgen excess: a hallmark of polycystic ovary syndrome

“…Decreased endometrial Glut4 gene expression is also regulated by ARs through binding to the GLUT promoter in rat models ( 15 ). Interestingly, one three-dimensional culture of mouse follicles in vitro demonstrated that high concentrations of insulin-like growth factor-1 (IGF-1) could inhibit mouse follicular development and maturation, which provides a possible explanation for the involvement of IGF-1 in the pathogenesis of ovulatory disorders in phenotype D in the absence of HA ( 2 , 16 ). Moreover, enhanced CYP17 activity in TCs is regulated by the PI3K/AKT pathway ( 17 ).…”

“…Patients should be thoroughly assessed to exclude other conditions that cause symptoms similar to PCOS. Although approximately 75% of patients with PCOS exhibit insulin resistance (IR), IR is not recognized as a diagnostic criterion ( 2 ).…”

The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria

“…This is mirrored in patient populations, as 50-80% of women with PCOS are affected by IR [2,3], 61% are overweight/obese [4], and >50% suffer from type 2 diabetes mellitus and metabolic syndrome before the age of 40 [5]. Moreover, it has been widely discussed that PCOS-associated hyperandrogenism and reproductive problems, may be a consequence of metabolic disorders, and thus have been defined as "metabolic hyperandrogenism" by some members of the field [6]; therefore, PCOS may be more accurately described as "metabolic reproductive syndrome," as defined previously by the National Institutes of Health (NIH) evidence-based methodology workshop of PCOS 2012 [7]. At the same time, elevated androgen levels intern promotes the accumulation and redistribution of adipose tissue in women, causing damage to insulin signaling pathways, creating a vicious cycle leading to further impaired glucose metabolism and IR [8].…”

“…Insulin may further indirectly affect steroidogenesis by altering the ovarian homeostasis between stereoisomers of inositol in ovarian tissuemyo-inositol (MI) and D-chiro-inositol (DCI) [6]. MI and DCI are secondary messengers of insulin, where MI is responsible for the intracellular glucose transport and is simultaneously converted to DCI, which facilitates glycogen storage.…”

“…The Rotterdam criteria describe someone as having PCOS if they have 2 of the 3 following clinical features: clinical and/or biochemical hyperandrogenism, ovulatory dysfunction, and polycystic ovaries according as measured by ultrasound analysis. Phenotype A (termed Endocrine-metabolic syndrome (EMS) type I by Unfer V. et al [6]) is the only phenotype which has all the above criteria and as such is sometimes termed "classic PCOS." In contrast, phenotypes B, C, and D have only 2 of these criteria and are often under or incorrectly diagnosed.…”