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Disturbed serum adipokines levels in normal-weight, normoinsulinemic four phenotypes of polycystic ovary syndrome

Study question: Altered adipose tissue secretion plays a central role in the meta- bolic abnormalities observed in PCOS. This study was conducted to determine the concentrations of adipokines in different phenotypes of PCOS women, hy- pothesizing that normal-weight, normoinsulinemic PCOS women, with mildest phenotype also present with changes in adipokine secretion compared to controls. Summary answer: There was no difference in adipokines serum levels be- tween different PCOS phenotypes. Lower levels of adiponectin and ghrelin, and higher levels of leptin and resistin were observed in all lean PCOS phenotypes without hyperinsulinemia compared to controls suggesting that other intrinsic PCOS factor is in the culprit of these abnormalities. What is known already: Women with PCOS have significantly elevated leptin and resistin, and lower adiponectin and ghrelin serum levels compared to healthy women. Whether these abnormalities are secondary to obesity/ab- dominal fat distribution/hyperandrogenism/hyperinsulinemia or represents the intrinsic PCOS abnormality is yet to be determined. There is a limited data on the adipokine serum levels in four main PCOS phe- notypes defined by the Rotterdam Criteria. The majority of them observed posi- tive association of serum adipokine concentrations and PCOS phenotype severity. Study design, size, duration: Observational, prospective study of 186 women with PCOS fulfilling Rotterdam criteria and 162 weight and age-matched women was conducted from 2009 to 2013. Five groups were created: A) O (Oligoovulation) + H (Hyperandrogenism) + P (Polycystic ovaries) (n = 102) ; B) O + H (n = 15), C) H + P (n = 27) ; D) O + P (n = 42) and E) (control group). Participants/materials, setting, methods: Body mass index (BMI), waist/ hip ratio (WHR) and hirsutism were evaluated. Serum concentrations of a leptin, adiponectin, resistin, ghrelin, androgens, sex hormone binding globulin (SHBG), glucose and insulin were measured. Free testosterone and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Results were analyzed using SPSS 17 for Windows. Main results and the role of chance: No association was found between the leptin, resistin, adiponectin and ghrelin serum levels with severity of PCOS pheno- type (all p > 0.05). We observed higher levels of leptin and resistin and lower levels of adiponectin and ghrelin in all PCOS phenotypes compared to control group (all p < 0.001). The most prominent finding was the lower adiponectin (p < 0.001) and ghrelin (p < 0.001) serum levels and higher levels of leptin (p < 0.001) and resistin (p < 0.001) in lean PCOS patients without hyperandrogenemia and insulin resis- tency (phenotype D) compared to healthy controls (group E).Limitations, reason for caution: Small sample size in group B. HOMA-IR was used instead of more reliable but technically difficult hyperinsulinemic- euglycemic clamp technique. With significant variations in PCOS presentation seen in different ethnic populations, generalizing data obtained from any single ethnic group to other population groups should be approached with caution. Wider implications of the findings: Although the O + P phenotype itself is under dispute, our data show that the normal-weight, normoinsulinemic PCOS women, who share this phenotype present with alterations in adipokines metabolism, the finding that was previously observed in PCOS women in general. This may suggest that some other intrinsic PCOS factor other than obesity, hyperandrogenism or hyperinsulinemia modulates the adipose tissue dysfunction which merit further research.

PCOS phenotypes; leptin; adiponectin; ghrelin; resistin

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