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.

Keywords: PCOS; dysmetabolism; endocrine syndrome; myo-inositol; phenotype D.

Figure 1

PCOS phenotypes. PCOS (polycystic ovary syndrome) and PCOM (polycystic ovarian morphology). Schematic illustration of the onset of the PCOS condition in the different phenotypes. Phenotypes A, B, and C share the hyperandrogenism condition and a metabolic onset of the syndrome, which leads to the occurrence of the esthetic manifestations of hyperandrogenism (acne, alopecia, hirsutism, and seborrhea), oligo-amenorrhea, and ovarian cysts. Phenotype D exhibits an ovarian onset of the condition, which directly causes an alteration in the menstrual cycle and the formation of ovarian cysts.

Figure 2

New classification for PCOS. PCOS (polycystic ovary syndrome), EMS (endocrine–metabolic syndrome), PCOM (polycystic ovarian morphology), and PCO (polycystic ovary). New combinations of different parameters indicate the phenotypes of an innovative PCOS classification. PCOS phenotype A is updated as “PCO-EMS type 1” with the presence of both hyperandrogenism and insulin resistance, the presence of PCOM and an endometrial thickness < 5 mm, and the presence of menstrual cycle alterations; PCOS phenotype C is updated as “PCO-EMS type 2” with the presence of both hyperandrogenism and insulin resistance, the presence of an endometrial thickness < 5 mm and PCOM, and the absence of menstrual cycle alterations; PCOS phenotype B is updated as “EMS” with the presence of both hyperandrogenism and insulin resistance, the presence of an endometrial thickness < 5 mm and the absence of PCOM, and the presence of menstrual cycle alterations. Subjects presenting PCO-EMS type 1, PCO-EMS type 2, and EMS share the same dermatological symptoms (acne, alopecia, and hypertrichosis) and the same related risk (diabetes, hypertension, and infertility). PCOS phenotype D is updated as “PCOS” with the absence of both hyperandrogenism and insulin resistance, the presence of PCOM and an endometrial thickness > 5 mm, and the presence of menstrual cycle alterations. Subjects with PCOS do not exhibit dermatological symptoms and share related risks (infertility, endometrial hyperplasia, and endometrial carcinoma) differing from those in subjects with EMS. ✓: feature present; X: feature absent.