Abstract

Metformin (MF), a first-line drug to treat type 2 diabetes mellitus (T2DM), alone and in combination with other drugs, restores the ovarian function in women with polycystic ovary syndrome (PCOS) and improves fetal development, pregnancy outcomes and offspring health in gestational diabetes mellitus (GDM) and T2DM. MF treatment is demonstrated to improve the efficiency of in vitro fertilization and is considered a supplementary drug in assisted reproductive technologies. MF administration shows positive effect on steroidogenesis and spermatogenesis in men with metabolic disorders, thus MF treatment indicates prospective use for improvement of male reproductive functions and fertility. MF lacks teratogenic effects and has positive health effect in newborns. The review is focused on use of MF therapy for restoration of female and male reproductive functions and improvement of pregnancy outcomes in metabolic and endocrine disorders. The mechanisms of MF action are discussed, including normalization of metabolic and hormonal status in PCOS, GDM, T2DM and metabolic syndrome and restoration of functional activity and hormonal regulation of the gonadal axis.

Highlights

  • Metformin (1,1-dimethyl biguanide hydrochloride) (MF), an orally administered biguanide, is a first-line drug for the treatment of type 2 diabetes mellitus (T2DM)

  • The data presented in the review convincingly prove that MF has an improving effect on reproductive functions both in women with polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM) and T2DM, and in men with

  • The effectiveness of MF therapy is due to a large number of different factors that must be taken into account when choosing this therapy and when developing a strategy for using MF

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Summary

Introduction

Metformin (1,1-dimethyl biguanide hydrochloride) (MF), an orally administered biguanide, is a first-line drug for the treatment of type 2 diabetes mellitus (T2DM). It reduces the adipose tissue mass and increases the tissue sensitivity to insulin, thereby reducing hyperglycemia, normalizing carbohydrate and lipid metabolism and preventing inflammation and oxidative stress in the tissues [1,2]. There is a large body of evidence for the effectiveness of MF therapy in restoration of reproductive functions and fertility in women with polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM) and T2DM, as well as to improve the effectiveness of the assisted reproductive technologies (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Pharmaceuticals 2021, 14, 42 only a brief description of the molecular mechanisms of MF action in target cells; these mechanisms are the focus of other review articles [17,18,19,20,21,22,23,24]

Summary of Cell Targets and Molecular Mechanisms of Action of Metformin
Pathophysiology of Polycystic Ovary Syndrome
The Use of Metformin in PCOS Women
The Mechanisms of Metformin Effects on Reproductive Functions in PCOS
Abbreviations
Protective efFect of Metformin against Excess Androgens in PCOS
Effects of Metformin on FSH-Activated Signaling in the PCOS Ovaries
The Effect of Metformin on the Production of Anti-Müllerian Hormone in PCOS
Effect of Metformin on Metalloproteinases in PCOS
Influence of Metformin on Inflammation and Lipid Status in PCOS
The Sensitivity of PCOS Women to Metformin Therapy
Metformin and Gestational Diabetes Mellitus
Metformin Treatment of Women with Diabetes Mellitus and Obesity
Effects Metformin on the Male Reproduction in Metabolic Disorders
Findings
Conclusions
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