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. 2021 Mar 9;40(1):11–29. doi: 10.5534/wjmh.210001

Table 3. Summary of metformin's effects on men's reproductive health: spermatogenesis.

Studies/comments Main findings
Cellular studies 1. Metformin is neither genotoxic nor cytotoxic and may potentially protect hyperglycemia-induced genomic instability in diabetic and non-diabetic adult male Wistar albino rats [54].
2. Metformin is not cytotoxic to Wistar rat Sertoli cells and can possibly be used safely in male diabetes patients of reproductive age [55].
Animal studies 1. Metformin increases the viability of pig sperms after 24 hours storage [56].
2. Metformin improves the quality of frozen-thawed dog semen during cryopreservation [57].
3. Metformin improves abnormalities in spermatogenesis and sperm motility in diabetic and non-diabetic male Wistar albino rats [54] and in diabetic male Sprague-Dawley rats [47].
4. Metformin limits testicular ischemia/reperfusion injury in male Wistar rats [58] and injury on sperm production in male Wistar albino rats [59].
5. Metformin reduces injury to the reproductive system induced by diabetes or obesity in rats [50,54,60].
6. Metformin improves fertility in obese male C57BL/6 mice [61,62].
7. Metformin has negative effects on sperm concentration, mobility and morphology in rabbits [46].
8. Metformin has a neutral effect on sperm viability and mobility in horses [63].
Human studies 1. An intervention trial conducted in Iraq: Metformin (850 mg bid for 12 weeks) may have a potentially harmful effect with regards to sperm count and activity [64].
Author’s comments 1. Metformin may protect against testicular injury and improve sperm quantity and quality in in rats or mice. However, this can not be proven in a human clinical trial.
2. Metformin may theoretically exert beneficial effects on spermatogenesis through its improvement of inuslin resistance, weight reduction and metaboic control. However, more human research is needed.
3. Interested readers may refer to review articles by Bertoldo et al [17], Ferreira et al [24], Faure et al [22], and Alzain et al [23].