Metformin in gynecological disorders: pathogenic insights and therapeutic implications

Ping Nie ¹ Minghua Wang ² Yan Mo ¹ Hong Zhou ¹ Qingbing Zha ¹ Gendie E Lash ³ Ping Li ^1*

• ¹ Jinan University, Guangzhou, China
• ² Longgang District People's Hospital of Shenzhen, Shenzhen, China
• ³ Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China

Metformin, the most widely used anti-diabetic drug, has been demonstrated to have various effects, including antioxidant, anti-inflammatory, anti-tumor and cardioprotective effects. Metformin is increasingly utilized to prevent or treat a wide range of gynecological disorders, as can be seen in epidemiological, clinical trials, animal and in vitro studies, due to its affordability and low toxicity profile. Trial findings for non-cancer conditions, such as endometriosis, premature ovarian failure (POF), and uterine fibroids, remain controversial and insufficient. However, most current clinical trials for polycystic ovarian syndrome and gynecological malignancies are ongoing phase II-III clinical trials. It has been demonstrated that the pharmacological effects of metformin target the IGF, AMPK, PI3K/AKT, MAPK and NF-κB and other signal transduction pathways, and has emerged as having potential in treatment of gynecological disorders. In this review, we discuss the biological impacts of metformin and mechanisms of action pertinent to the treatment in different gynecological disorders.