Role of Nesfatin-1 and Nicotinamide in Infertile Women With Polycystic Ovary Syndrome

Role of Nesfatin-1 and Nicotinamide in Infertile Women With Polycystic Ovary Syndrome

evaluation of the potential role of circulating Nesfatin-1 and Nicotinamide in patients with polycystic ovary syndrome.

and detection the correlation between Nesfatin-1 and body mass index (BMI), Waist hip ratio (WHR), blood glucose, insulin, insulin resistance, lipid profiles, prolactin, LH, FSH, estrogen, progesterone, testosterone and dopamine.

• Nesfatin-1 is an 82-amino acid polypeptide derived from the nucleobindin 2 (NUCB2) precursor proteins.
• It is a newly identified peptide. It is released from several tissues including forebrain, hindbrain, brainstem, spinal cord and adipose tissues.
• It plays an important role in hypothalamic pathways such as feeding inhibition, locomotion, stress modulation, thermogenesis, and reproduction.
• Several studies had demonstrated that nesfatin-1 associated with body mass index (BMI), insulin resistance and inflammatory response disorders.
• Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. It is characterized by hyperandrogenism, multiple ovarian cysts, oligomenorrhea/amenorrhea. Many mechanisms had been reported to be responsible for the pathophysiology of PCOS. The condition is thought to be interactions between hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal axis and metabolic disorders.
• The circulating level of nesfatin-1 in PCOS patients is controversial. Some studies reveal lower nesfatin-1 serum levels while others reveal higher level.
• Women with PCOS may have reduced dopamine production from the hypothalamus and elevated prolactin concentrations and this mechanism may be responsible for reproductive disorder.
• In PCOS, stimulation of reactive oxygen species (ROS) generation from mononuclear cells (MNCs) by hyperglycemia . The superoxide radical in particular is a ROS that is generated by the activity of membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
• Dopaminergic (DA) neurons are highly susceptible to ROS. DA is relatively unstable molecule and undergoes auto-oxidative metabolism in nigro striatal tract system, leading to ROS production. Nicotinamide can reduce hypothalamic dopamine in postnatal brains results in dopamine-deficient phenotypes. Nicotinamide prevents DA release induced by long-term perinatal asphyxia.

Inclusion Criteria:

• PCOS patients in the age range 18 - 40 years old.

• Diagnosis of PCOS is based on the 2003 ESHRE/ASRM diagnostic criteria, according to which patients who had at least two of the following conditions are accepted as having PCOS:

  1. Oligo or anovulation, defined by the presence of oligomenorrhea or amenorrhea, confirmed by luteal progesterone and normal serum follicle stimulating hormone (FSH) levels (1.0-10.0 IU/L).
  2. Clinical hyperandrogenism signs which was defined as the presence of at least one of the following three features: hirsutism, acne, and androgenic alopecia. Biochemical hyperandrogenism was defined as a serum testosterone (T) level >60 ng/dL (>2.08 nmol/L).
  3. PCOS manifestation was defined as the presence of >12 unilateral follicles 2-9 mm in size on the ovary or having the least unilateral ovary volume of 10 cm3 by ultrasonography (the measurement was performed when there was no follicle >10 mm). Ovarian volume was calculated by the formula [0.5× ovarian length × thickness × width]. In the case of transabdominal ultrasonography, the presence of at least 10 unilateral antral follicles was required.

Exclusion Criteria:

• Patients (age <18 or > 40years),
• Other endocrinology diseases as diabetes mellitus or thyroid disorders, Brain disorders as pituitary adenoma or tumour or brain tumours or masses,
• Chronic diseases such as cardiovascular, hepatic, hematologic, chronic renal failure, hypertension, and cancer,
• Use of oral contraceptives, antiandrogenics, glucocorticoids, antihypertensives, antidiabetics and anti-obesity drugs as well as the cigarettes, alcohol, and patients unwilling to participate in the study.