Adjunctive melatonin and sildenafil, enhances antioxidant defense in metformin-treated polycystic ovary syndrome patients: A randomized study - 23/03/26

Doi : 10.1016/j.jogoh.2026.103165

Mohammad Farajneia Hosseinabad ^a, Elahe Masnavi ^b, Parvin Alsadat Eslamnik ^b, Ali Taheri Mirghaed ^a, Elahe Piraee ^a, Asma Siavashpour ^c, Zahra Asadikalemeh ^b,^⁎ , Amir Hossein Doustimotlagh ^d,^⁎

^a Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran

^b Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran

^c Department of Occupational Health Engineering, School of Health, Yasuj University of Medical Sciences, Yasuj, Iran

^d Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

^⁎ Corresponding author: Zahra Asadikalemeh, Department of Gynecology and Obstetrics, Yasuj University of Medical Sciences, Yasuj, Iran Department of Gynecology and Obstetrics Yasuj University of Medical Sciences Yasuj Iran ^⁎⁎ Co-corresponding author: Amir Hossein Doustimotlagh, Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran, Tel: +989375317741 Department of Clinical Biochemistry Faculty of Medicine, Yasuj University of Medical Sciences Yasuj Iran

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Highlights

•	Polycystic ovary syndrome (PCOS) is a serious clinical complication
•	There is no precise cellular and molecular mechanism for PCOS so far
•	Several studies mentioned the role of oxidative stress in PCOS
•	We found that oxidative stress plays an important role in PCOS pathogenesis
•	Metformin, melatonin and sildenafil attenuated oxidative stress in PCOS patients

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Abstract

Objective

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder, the exact causes of which are still not known. However, studies have emphasized the role of oxidative stress in the pathogenesis of PCOS. The aim of this study is to investigate the effect of sildenafil and melatonin on oxidative stress markers in PCOS patients.

Study design

51 PCOS patients were randomly divided into three groups and received treatment for three months. Group 1, only received metformin; Group 2, received melatonin + metformin, and Group 3 received sildenafil + metformin. Blood samples were collected before and after the treatment started, and serum levels of malondialdehyde (MDA), nitric oxide (NO), ferric-reducing antioxidant power (FRAP), protein carbonyl (PC) and total thiol (T-SH) were measured.

Result

The findings of the study demonstrated a decline in the mean levels of MDA and PC in the metformin-only, sildenafil, and melatonin groups. This decline was statistically significant for MDA in the metformin-only group (P=0.008) and the sildenafil group (P=0.04), and for PC in the metformin-only group (P=0.005) and melatonin group (P=0.04). The antioxidant markers such as T-SH (P=0.009) and FRAP (P=0.03) levels significantly increased in the melatonin group after the intervention.

Conclusion

Overall, biomarkers of oxidative stress improved in the metformin-only, melatonin, and sildenafil groups, suggesting that these drugs may have protective effects in PCOS patients. However, further studies are needed to determine their effectiveness.

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Keywords : polycystic ovary syndrome, metformin, melatonin, sildenafil, oxidative stress