**2. Etiology**

5 to 10% according to the NIH 1990 criteria, from 10 to 15% according to the AE-PCOS 2006 criteria, and from 6 to 21% when the Rotterdam criteria are applied [7]. East Asian subjects (Korean, Chinese, and Thai) appear to have a lower prevalence of PCOS (about 5%) compared

**Title NIH 1992 Rotterdam 2003 AE-PCOS 2006 NIH 2012 extension of Rotterdam** 

• Clinical or biochemical androgen excess • Ovarian dysfunction and/ or polycystic ovaries

• Clinical or biochemical androgen excess • Oligo- or anovulation • Polycystic ovaries

criteria

Exclusion Exclusion of other androgen excess and other similar etiology

**2003**

Need both criteria • Need two of three criteria

gen excess • Oligo- or anovulation • Polycystic ovaries

• Clinical or biochemical andro-

• Specifically identifying the four

**A.** Androgen Excess + Ovulatory Dyfunction + Polycystic

**B.** Androgen Excess + Ovulatory

**C.** Androgen Excess + Polycystic

**D.** Ovulatory Dysfunction + Polycystic Ovarian Morphology

sub-phenotype:

Ovaries

Ovaries

Dysfunction

One systematic review and meta-analysis showed the incidence of PCOS phenotypes using the 2012 NIH criteria was 50% for phenotype A, 13% for phenotype B, 14% for phenotype C,

Patients with PCOS often have comorbidities such as obesity, insulin resistance/type II diabetes mellitus (Type II DM), dyslipidemia, hypertension/cardiovascular disease, infertility/subfertility, or cancer. One systematic review and meta-analysis demonstrated that women with PCOS had a pooled prevalence of 61% for overweight [body mass index (BMI) > 25], 49% for obesity (BMI > 30), and 54% for central obesity [13]. Insulin resistance (IR) is present in 50–80% of these women, which is associated with obesity [14, 15]. Both lean (30%) and obese women

to Caucasian women (11–20%) [11].

(70%) with PCOS show decreased insulin sensitivity [16].

and 17% for phenotype D [12].

**Table 1.** Diagnostic criteria for PCOS.

**1.3. Comorbidities**

Criteria • Clinical or

92 Debatable Topics in PCOS Patients

biochemical androgen excess • Rare ovulations

Restriction Need both criteria Need two of three

The etiology of PCOS is still not clear. A systematic review suggested that post-natal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis [27]. Recently, some clinical studies have confirmed that human fetal androgen excess promotes PCOS development after birth by checking infant blood levels at term [28]. The circulating androgen levels of the human female fetus in the second trimester can increase into the male range and mid-gestational amniotic testosterone levels in female fetuses of PCOS mothers may be higher than those in normal mothers, which might influence fetal development [28]. Another review article mentioned that the fetal ovary is more likely to produce an excess of androgens in response to maternal human chorionic gonadotropin (hCG) in subjects genetically predisposed to PCOS [29]. Furthermore, some genetic variations are associated with PCOS. For example, DENND1A is found in the cytoplasm and nuclei of ovarian theca cells. Over expression of DENND1A variant 2 results in a PCOS-like phenotype, and knock-down of DENND1A variant 2 in PCOS theca cells reversed this phenotype [30]. In addition, a recent review showed that genome-wide association studies (GWAS) have identified some loci containing genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in PCOS [31].
