Endocrine Abstracts

Dysregulation of the neuroendocrine system is a key element in the pathogenesis of polycystic ovary syndrome (PCOS). Orexins (hypocretins) are a new class of hypothalamic neuropeptides that influence sleep-wake rhythms and the state of energy metabolism. In addition, their receptors expresses in peripheral tissues, including the endocrine system. Data have emerged on the role of orexins in the regulation of the reproductive system and, in particular, ovulation, through a direct effect on the hypothalamic-pituitary-ovarian axis, and their stimulating effect on GnRH neurons has been described.

Objective: To study orexin status in women with PCOS and its role in the pathogenesis of the disease.

Methods: The study involved women 18-39 years old: 20 patients with PCOS with a body mass index (BMI) ≥25 kg/m² (group 1), and 20 women with PCOS and BMI<25 kg/m² (group 2). The diagnosis of PCOS based on the Rotterdam criteria (2003). The control group consisted of 20 healthy women with a regular menstrual cycle and BMI <25 kg/m². We determined the levels of orexin A, LH, FSH, testosterone, insulin in the blood serum in all three groups in the 1st phase of the menstrual cycle (3-7 days of cycle) or against the background of a menstruation delay for more than 2 months (in patients with PCOS).

Results: All three groups were age-matched. In group 1, the median BMI was 30.8 kg/m² [26.6; 34.6], in group 2 - 21.4 kg/m² [19.2; 22.4], in the control group - 20.9 kg/m² [20.0; 22.8]. The median level of orexin A was significantly lower in the group of patients with PCOS and BMI ≥25 kg/m², compared with the group of PCOS with normal BMI and healthy women: 1.32 ng/ml [0.29;3.56], 5.77 ng/ml [3.34;9.87] and 11.06 ng/ml [8.41;17.49], respectively (P<0.05). In the overweight PCOS group, insulin level was significantly higher compared to patients with normal weight and healthy participants: 13.7 [8.3; 23.7] mIU/l; 7.2 [5.2; 9.1] mIU/l and 6.2 [5.0; 8.6] mIU/l, respectively (P<0.05). We found a negative correlation between the level of orexin A and BMI, orexin A and insulin: the higher was the BMI and the insulin level; the lower was the level of the neuropeptide orexin, respectively.

Conclusion: Orexin A is a potential marker of ovarian hyperandrogenism. It also reflects the severity of insulin resistance, which is one of the main triggers in pathogenesis of PCOS.