Analysis of insulin like peptide-5 (İNSL5) levels and their association between hormonal and metabolic parameters in polycystic ovary syndrome patients

Objectives Polycystic ovary syndrome (PCOS) is the most common reproductive disorder that onsets peripubertally and increases morbidity by affecting quality of life. PCOS is characterized by menstruel cycle problems such as oligo-amenorrhoea and anovulation with hyperandrogenemia signs such as hirsutism and acne. Insulin like peptide 5 (INSL5) is a relaxine/insulin family member gut-peptide hormone that is expressed by various tissues including the hypothalamus, pituitary and ovary. INSL5 knockout mice showed infertility in both sex due to notable decrease in sperm motility and irregular menstruel cycle during animal genetic researches. It is suggested in limited number of human studies that INSL5 levels are elevated in serum and in close correlation with diagnostic parameters of PCOS. Pathophysiologic role of INSL5 remains to be elucidated in humans and further researches are needed. Anti Mullerien hormone (AMH) is a member of the transforming growth factor-beta (TGF-β) family that is produced from ovarian granulose and teka cells. It induces follicular atresia by decreasing FSH sensitivity of the follicule and inhibiting follicular development in the ovarien tissue. It has been suggested that AMH levels are increased two to three fold in PCOS patients according to the studies that incvestigates AMH role and serum values on PCOS pathogenesis. PCOS is a very common disorder that might lead to metabolic and cardiovascular complications on the long term. The search of a novel biomarker with high specifity and sensitivity in the need of PCOS diagnosis is one of the trending research topics. In this study, it was aimed to investigate serum insulin like peptide 5 (INSL5) levels in patients diagnosed with PCOS and to evaluate the relationship of INSL5 between AMH, hormonal and metabolic parameters. Materials and Methods This study was conducted with 45 polycystic ovarian syndrome patients between the ages of 18-35, who had not received medical treatment in the last six months, and 35 healthy women at the same age range as control group in Bolu Abant Izzet Baysal University School of Medicine, Department of Endocrinology and Metabolism. Demographic information, waist and hip circumference measurements, height and weight measurements were performed. Hyperandrogenemia symptoms including hirsutism, alopecia, acneiform lesions were evaluated by physical examination. Venose blood samples were measured on the 2-5th days (follicular phase) of menstruel cycle. AMH and INSL5 were measured from same serum samples. Pelvic ultrasonography was performed on the same day to examine ovarian size and follicle numbers. Results In the present study, INSL5 was 12.5 (3.8- 59.5) ng/ml in the PCOS group and 15.5 (5.3-37.4) ng/ml in the control group. There was no statistically significant difference in INSL5 level between the groups (p=0.103). AMH level was statistically significantly higher in PCOS group compared to the control group (p <0.001). As a result of multivariate logistic regression analysis, AMH was found to be a determinant factor for PCOS. AMH cut-off value for PCOS diagnosis was 5.04 ng/ml (% 75.6 sensitivity, % 74.3 specificity). INSL5 was negatively correlated with body mass index (BMI), free androgen index (FAI), insulin, HOMA-IR, triglyceride, total cholesterol, LDL, fat mass, fat percentage and positively correlated with sex hormone binding globulin (SHBG) in PCOS group. FAI was found to be an independent factor for PCOS in multivariate linear regression analysis (p=0.024). Conclusion There was not any difference in INSL5 levels between PCOS patients and healthy subjects, suggesting that the peptide does not have a diagnostic value in PCOS. Negative correlation between INSL5 and the parameters that affects PCOS diagnosis and pathogenesis such as FAI, insulin, HOMA-IR and atherogenic lipid profile supports the studies suggesting that this peptide might be related to glucose and lipid metabolism. INSL5 level also showed negative correlation with fat percentage and fat mass. The results suggest that there might be a relationship between INSL5 level and adipose tissue. In our study, the determination of SAI that represents hyperandrogenemia which is an important clinical feature of PCOS, as an independent parameter determining INSL5 levels, indicates that further studies are required to evaluate the relationship between INSL5 and PCOS.