Table 1.
Summary of studies that evaluated the effect of statins on male reproductive parameters.
| Ref/Author | Country | Year | Study Population | Type of Statin | Statin Dose | Effect of Statin on Fertility |
|---|---|---|---|---|---|---|
| Animal findings | ||||||
| [36] Akdeniz et al. | Turkey | 2020 | Animal | Atorvastatin | 20 mg | (−) Decrease in the number of Sertoli cells, Spermatogonia, Spermatocytes. (−) Decrease in seminiferous tubule diameter. (−) Loss of cellular boundaries in the testes. Overall effected spermatogenesis |
| [37] Zangoie et al. | Iran | 2019 | Animal | Atorvastatin | 100 mg/kg | (+) Increased the amount of viable sperm. (+) Prevented testicular injury against busulfan. |
| [38] Naeimi et al. | Iran | 2017 | Animal | Atorvastatin | 10/20/50 mg/kg | (−) Decreased radiation induced oxidative stress. (−) Decreased level of testosterone. (+) Increased testicular tubal diameter and epithelial thickness |
| [39] Shalaby et al. | Egypt | 2003 | Animal | Simvastatin | 40 mg daily | (+) Increased the weight of the testes. (+) Increased sperm count. (+) Increased sperm motility. (−) Decreased sperm abnormalities. (+) Maintained the structure of the seminiferous tubules. |
| [40] Cui et al. | China | 2017 | Animal | Fluvastatin | 6 mg/kg | (+) Reversed spermatogenic damage. (+) Protective effect on the seminiferous tubules. (+) Protective against testicular atrophy. (+) Protective effect on spermatogonia, Sertoli cells, and Leydig cells. (+) Increases the expression of mTOR. |
| [41] Gurel et al. | Turkey | 2019 | Animal | Fluvastatin | 6 mg/kg | (−) Reduced oxidative stress. (+) Increased testosterone levels. (+) Protective effect on seminiferous tubules and spermatogenic cells. (+) Protective effect on sperm count. |
| [13] Leite et al. | Brazil | 2014 | Animal | Rosuvastatin | 3 or 10 mg/kg | (−) Decrease testosterone concentration. (−) Delayed epididymal development. (+) Promoted the development of abnormal seminiferous tubules. |
| [14] Leite et al. | Brazil | 2017 | Animal | Rosuvastatin | 5 and 40 mg daily | (−) Testosterone was decreased. (−) Decreased fertility, based on post-implantation loss. (−) Decreased production of sperm and mature spermatids. (−) Reduction in the rate of progressive sperm. (+) Increased sperm head abnormalities. (−) Loss of structure of the seminiferous tubules. |
| [42] Silva et al. | Brazil | 2020 | Animal | Rosuvastatin | 5 mg/kg | (−) Reduced ejaculation frequency. (−) Hyperplasia of clear cells in the proximal region of the cauda epididymis. |
| [43] Heeba et al. | Egypt | 2015 | Animal | Rosuvastatin | 10 mg/kg | (+) Improved sperm count and motility. (−) Decreased testicular nitric oxide. (+) Maintained the weight of the testes and structure of the epididymis. (−) Showed less degeneration of seminiferous tubules with shedding of germ cells. |
| [44] Farsani et al. | Iran | 2018 | Animal | Pravastatin | 20 mg/kg | (+) Maintained testicular volume, seminiferous tubule diameter, and germinal epithelium. (+) Maintained epididymal sperm count. (+) Maintained the number of spermatogonia, spermatocytes, and Sertoli cells. (+) Showed radical scavenging properties. |
| [45] Dursun et al. | Turkey | 2014 | Animal | Pravastatin | 30 mg/kg | (+) Showed antioxidant properties. |
| [44] Esrafil et al. | Iran | 2017 | Animal | Pravastatin | 20 mg/kg | (−) Reduced doxorubicin induced oxidative damage. (+) Showed antioxidative effects. |
| [46] Kassan et al. | Spain | 2010 | Animal | Pravastatin | (+) Showed antioxidant properties. (−) Reduced lucigenin induced O2 levels. |
|
| Human findings | ||||||
| [47] Pons-Rejraji et al. | France | 2014 | Human | Atorvastatin | 10 mg | (−) Decreased the number of spermatozoa. (−) Decreased vitality, motility, and morphology of sperm. (−) Alterations in prostatic and epididymal function. (−) Decreased spontaneous acrosome reacted spermatozoa. |
| [19] Bernini et al. | Italy | 1998 | Human | Pravastatin | 20 mg/day | (+/−) No change in testosterone. (+/−) No change in motility, morphology, and sperm count. |
| [48] Travia et al. | Italy | 1995 | Human | Pravastatin | 40 mg/day | (+/−) No change in testicular steroidogenesis. (+/−) No change adrenocortical function. |
| [9] Dobs et al. | U.S.A | 1993 | Human | Pravastatin | 20 to 80 mg daily | (+/−) No change in testosterone levels. (−) Decreased sperm motility. |
| [11] Tada et al. | Japan | 2015 | Human | Rosuvastatin | 2.5 mg daily | (−) Decreased spermatozoa. (−) Decreased sperm count. (−) Decreased sperm motility. |
| [49] Purvis et al. | Norway | 1992 | Human | Simvastatin | 40 mg daily | (+/−) No effect on the quality of sperm. (+/−) No effect on testosterone. |
| [50] Azzarito et al. | Italy | 1992 | Human | Simvastatin | 20–40 mg daily | (+/-) No change in testosterone. |
| [51] Rossato et al. | Italy | 1993 | Human | Simvastatin | 10 mg daily | (+) Increased levels of androstenedione. (−) Thought to have an inhibitory effect on 17-hydroxysteroid-de-hydrogenase. |
| [52] Al-Hilli et al. | Iraq | 2017 | Humans | Simvastatin | 20 mg daily | (+) Improved sperm motility. (−) Reduced the degree of lipid peroxidation. (+) Improved sperm morphology and viability. (+) Improved sperm formation and maturation. |
| Mammalian tissue/cells | ||||||
| [53] Smals et al. | The Netherlands | 1991 | Human Testicular Tissue | Simvastatin | 0.01 and 0.1 μM | (+) A dose of more than 0.1 μM Effects 17-hydroxysteroid-de-hydrogenase. |
| [54] Imaeda et al. | Japan | 2001 | Mammalian cells | Fluvastatin | 1–10 mM | (−) Decreased DNA tail movement. (−) Reduced DNA damage. (+) Presented radical scavenging properties |
| [55] Okubo et al. | Japan | 2019 | Renal Cancer Cells | Fluvastatin | (+) Shows increased mTOR expression. | |
| [56] Wang et al. | China | 2021 | Neuronal Cells | Fluvastatin | (+) Fluvastatin reduced O2 induced damage of neuronal cells in a dose dependent manner. | |
(−) = negative or adverse effect; (+) = Positive effect.