Introduction

Several studies have focused on the diagnostic criteria for polycystic ovary syndrome (PCOS), which have been the subject of debate for many years. As the name suggests, PCOS is a syndrome, not a disease, which means a more or less complete set of phenotypic characteristics, variously associated, with the lack of a constant element on which the diagnosis could be based (“gold standard”). According to the predominance of a particular symptom, patients with PCOS are directed to various specialists who, therefore, have a partial and oriented view of the syndrome. Because of its prevalence, PCOS is often associated with other conditions with symptoms that are sometimes mistakenly viewed as being directly linked to PCOS. A significant example here is obesity followed by metabolic abnormalities. The clinical signs and biological disorders related to obesity often “pollute” the presentation of PCOS phenotype, thereby creating discrepancies in the literature. Other conditions, less frequent than obesity, may be associated with PCOS and may be unrecognized if their symptoms overlap with those of PCOS. Finally, with the advent of new diagnostic markers, we recognize several moderate or latent forms of PCOS. This makes it especially difficult to set diagnostic thresholds for different markers allowing separation, with good sensitivity and good specificity, of “normal” women from patients with PCOS. Thus, as posed in the title, the diagnostic criteria must be reassessed.

Historical background

In 1935, Stein and Leventhal designated PCOS as a syndrome due to its association with varying degrees of hirsutism, chronic anovulation, bilateral ovarian enlargement, and obesity. With the advent of hormonal assays, the diagnostic criteria have been for some time based on the increase in serum androgen and luteinizing hormone (LH) levels, with an increased LH/follicle-stimulating hormone (FSH) ratio. In 1990, during an expert conference sponsored in part by the National Institute of Child Health and Human Disease (NICHD) of the NIH , the participants agreed that the major diagnostic criteria for PCOS should include (in the order of importance) i) hyperandrogenism (HA) and/or hyperandrogenemia, ii) menstrual dysfunction, and iii) exclusion of other known disorders.

This definition has prevailed for many years, ignoring the advent of ultrasound (U/S) and the possibility of reverting to a morphological description of polycystic ovaries (PCOM; polycystic ovarian morphology). It must be recognized that in the 1980–1990s, the U/S criteria had long been uncertain and variable. Based on a rigorous evaluation of these criteria, the Rotterdam consensus conference held in 2003 decided to retain the following sonographic description of PCOM: either 12 or more follicles per whole ovary measuring 2–9 mm in diameter, or increased ovarian volume (>10 cm ³ ). This definition was then added to the NIH criteria, thus introducing a classification based on three items ( Table 1 ). The most significant advance in this consensus conference was the requirement of at least two items. This flexible association generates the possibility of four phenotypes ( Table 2 ) with various concerns, which are not accepted universally. Certainly, the phenotype without overt HA (phenotype D) is the most controversial .

Indeed, concerned with the “laxity” of this definition, some have later proposed to adjust it by making the criterion “HA” a mandatory prerequisite (AES classification) . At present, the classification of Rotterdam is the most used, but with varying frequency depending on the country and medical specialties. Whether this classification has been well understood remains unclear. For example, during a large survey of IVF centers in the world , >80% of the physicians reported using this classification; however, almost 40% also considered HA as a mandatory criterion. In addition, this classification is >10 years old and has not been updated, leading to inconsistencies in the literature.

Historical background

In 1935, Stein and Leventhal designated PCOS as a syndrome due to its association with varying degrees of hirsutism, chronic anovulation, bilateral ovarian enlargement, and obesity. With the advent of hormonal assays, the diagnostic criteria have been for some time based on the increase in serum androgen and luteinizing hormone (LH) levels, with an increased LH/follicle-stimulating hormone (FSH) ratio. In 1990, during an expert conference sponsored in part by the National Institute of Child Health and Human Disease (NICHD) of the NIH , the participants agreed that the major diagnostic criteria for PCOS should include (in the order of importance) i) hyperandrogenism (HA) and/or hyperandrogenemia, ii) menstrual dysfunction, and iii) exclusion of other known disorders.

This definition has prevailed for many years, ignoring the advent of ultrasound (U/S) and the possibility of reverting to a morphological description of polycystic ovaries (PCOM; polycystic ovarian morphology). It must be recognized that in the 1980–1990s, the U/S criteria had long been uncertain and variable. Based on a rigorous evaluation of these criteria, the Rotterdam consensus conference held in 2003 decided to retain the following sonographic description of PCOM: either 12 or more follicles per whole ovary measuring 2–9 mm in diameter, or increased ovarian volume (>10 cm ³ ). This definition was then added to the NIH criteria, thus introducing a classification based on three items ( Table 1 ). The most significant advance in this consensus conference was the requirement of at least two items. This flexible association generates the possibility of four phenotypes ( Table 2 ) with various concerns, which are not accepted universally. Certainly, the phenotype without overt HA (phenotype D) is the most controversial .

Indeed, concerned with the “laxity” of this definition, some have later proposed to adjust it by making the criterion “HA” a mandatory prerequisite (AES classification) . At present, the classification of Rotterdam is the most used, but with varying frequency depending on the country and medical specialties. Whether this classification has been well understood remains unclear. For example, during a large survey of IVF centers in the world , >80% of the physicians reported using this classification; however, almost 40% also considered HA as a mandatory criterion. In addition, this classification is >10 years old and has not been updated, leading to inconsistencies in the literature.

What were the benefits of applying the Rotterdam criteria?

First, this classification now allows recognizing moderate phenotypes lacking either HA or oligo-anovulation (OA). As these phenotypes are not recognized by the NIH classification, the first consequence has been the increase in the prevalence of PCOS by about 50% in different populations . This increase in prevalence appears to be divided equally between the C and D phenotypes (isolated HA or OA, respectively). In addition, the Rotterdam classification considers the ethnic variations in the phenotypic expression of PCOS, which explains why the prevalence of PCOS as defined by the Rotterdam criteria was higher in some populations than in others .

Conversely, the Rotterdam consensus conference has specified that the isolated presence of PCOM on U/S was not sufficient to make the diagnosis of PCOS. This is extremely important because, although using different criteria, a large number of studies from different countries reported a prevalence of 20–30% of PCOM in the general population of women exhibiting neither HA or OA (reviewed in Ref. ). Furthermore, using the strict U/S criteria retained in 2003, the prevalence of asymptomatic PCOM in the general population has increased markedly in recent years, reaching 80% in some series. This is clearly an artificial deviation and the reasons are outlined later.