The Role of CYP450 in Women with Polycystic Ovary Syndrome and Elevated Gonadal Hormone and DHEA Concentrations

Abstract

The polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by polycystic ovarian morphology, hyperandrogenism and ovulatory dysfunctions. One of the key molecular contributors to its pathophysiology is the altered activity of enzymes belonging to the Cytochrome P450 (CYP450) superfamily, which plays a central role in steroid hormone biosynthesis and metabolism. This study was designed to be a case-control study conducted in the Kamal Al Sammarae hospital for fertility and IVF during the period from 1 August 2024 to 1 September 2025. In this study, 100 blood samples were collected from PCOS women aged between  (20-35) years who were enrolled in this study. These women were complaining of polycystic ovary syndrome (PCOS), documented according to the Rotterdam criteria. Also, 100 Non-PCOS women were selected as a control group; the non-PCOS control group matched with the PCOS group by age and BMI. The results of gonadal hormone analysis in PCOS cases revealed that the mean level of TSH was (2.62± 0.12) compared to the control group (1.81±0.08), and the mean level of LH in the patient group was (7.78±1.12) in comparison to the controls (3.72±0.54). On the other hand, FSH levels were (5.94±0.21) in the PCOS women compared to the healthy control (1.97±0.12) and the mean level of Free T3 was (0.61±0.05) compared to the controls (0.01±0.03) with highly significant variations (P≤0.01) respectively. In addition, the mean level of Prolactin in PCOS women was (12.22± 0.71) in comparison to the controls (11.73±0.35) with a non-significant difference (P=0.53). The mean levels of Insulin in POCS women was (12.85±1.10) compared to the controls (13.43±0.36) with a non-significant variation (P=0.61), while the mean level of FBS in the patient group was (7.95±0.37) compared to the healthy group (0.23±0.14), and the mean level of HOMAIR was (5.43± 0.86) in comparison to the controls (1.58±0.22), with highly significant differences (P≤0.01) respectively. Mutations were detected in rs6466, rs6474, rs147821751, and rs6467 genes, and GG was changed to GA of G/A heterozygous allele in samples 1,5,6,7,8,12,15,16,18 and 19. While it was changed to AA of A/C heterozygous allele in samples 3 and 17 of rs6466 in comparison to the controls. However, the CC were the CC nucleotides were changed to CT sequence of C/T heterozygous allele.