Effect of metformin on semen quality

Abstract

Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.Uniterms: Metformin/effects. Metformin/review. Metformin/semen quality. Sperm/study. Testosterone. Oxidative stress. 5'-AMP activated protein kinase. INTRODUCTIONMetformin, a biguanide-derivative antidiabetic drug, is the most widely used oral agent in humans (Brinkmann, Brixius, 2015;Chhetri, Thapa, Van Schepdael, 2014). It is the first-line drug for the treatment of type 2 diabetes, particularly, in overweight and obese patients with normal kidney function (American Diabetes, 2009;George, Joseph, 2014;Hung et al., 2015). In addition, recent research has proposed that metformin alone or in combination with insulin may be safe to treat gestational diabetes and does not increase the risk of metabolic acidosis (Huang, Castelino, Peterson, 2015; Kitwitee et al., 2015). Metformin's mechanism of action involves suppression of hepatic gluconeogenesis (Ferrannini, 2014; Foretz et al., 2010;Todd, Florez, 2014). One concern that has been raised relevant to metformin usage is that the consensus panel of diabetes felt that metformin should be considered for diabetes prevention even in non-diabetic individuals (i.e., pre-diabetic or obese individuals). This concern increases the use of this drug by these groups (American Diabetes, 2009;Hostalek, Gwilt, Hildemann, 2015;Manu et al., 2015;McGavock, Dart, Wicklow, 2015).Over the last decade, various experimental and clinical studies have linked metformin with sperm function, and thus with male factor infertility Ferreira et al., 2015); however, such direct link has not been established. In this review, we provide fresh and comprehensive understanding of the effect of metformin, as a universally used oral agent, on semen quality (i.e., sperm quantity and quality). To do this, we searched the MEDLINE electronic database for English-language articles and abstracts reported using the key words 'metformin' and 'sperm'. The references from selected articles were reviewed and used if relevant. Effect of metformin on sperm parameters Positive effectsTo date, the majority of studies linking metformin to sperm parameters are nonclinical. In his study on streptozotocin-induced diabetic rats, Attia, Helal, Alhaider (2009) made the seminal observation that metformin decreases the diabe...

Understanding and treating ejaculatory dysfunction in men with diabetes mellitus

“…157,158 A systematic review of all the different pharmacotherapies employed to treat RE has found sympathomimetics achieved an antegrade ejaculate in 28%, whereas for anticholinergics such as imipramine and brompheniramine this was 22%. 7 It is important to note that although insulin can directly improve male reproductive hormone levels in animal models [160][161][162] and sperm parameters in men, 163,164 and there is some evidence for such direct effects of oral anti-hyperglycaemic agents, [165][166][167] evidence for such direct positive effects on EjD attributable to DM, such as RE, is yet to be established.…”

“…It is important to note that although insulin can directly improve male reproductive hormone levels in animal models 160–162 and sperm parameters in men, 163,164 and there is some evidence for such direct effects of oral anti‐hyperglycaemic agents, 165–167 evidence for such direct positive effects on EjD attributable to DM, such as RE, is yet to be established.…”