SUMMARY: DOES VIAGRA, CIALIS OR LEVITRA AFFECT SPERM
In this controlled animal study, use of Sildenafil (Viagra), Tadalafil (Cialis) and Vardenafil (Levitra) impaired male fertility with a decrease in testosterone levels and increase in oxidative stress, causing a significant decrease in the number of spermatocytes and sperm after 12 weeks of use.
doi.org/10.1371/journal.pone.0241509
Background
Main article: Increase your Sperm Count
Sildenafil (Viagra), Tadalafil (Cialis) and Vardenafil (Levitra) is commonly prescribed for management of erectile dysfunction in men. Conversely, oxidative stress is believed to the leading cause of infertility among men.
Previous animal studies identified a significant link between reactive oxygen species (ROS) production and erectile dysfunction. Subsequent human studies, have since confirmed oxidative stress plays a vital role in erectile dysfunction which can be reduced by antioxidant enzymes.
Interestingly, Sildenafil and Vardenafil studies have also reported positive effects on markers of oxidative stress. However, the potential secondary benefits of erectile dysfunction medication on male fertility remains to be studied in detail.
Aim
To evaluate changes in testosterone levels and antioxidant activity following treatment of rabbits with Sildenafil, Vardenafil and Tadalafil.
Methodology
Twenty male New Zealand white rabbits (7 months old) housed in a climate and light controlled environment, were randomly allocated into 4 even groups; control, Sildenafil (1.48mg/kg), Tadalafil (0.285 mg/kg) and Vardenafil (0.285 mg/kg).
The erectile dysfunction drug (EDD) groups were administered their respective drug, 3 times a week for a total of 12 weeks. Blood samples were collected from all rabbits at week 1, 6 and 12, with liver and teste samples collected at the end of the experiment for further analysis.
A comprehensive list of hormones and proteins was the analysed to capture and changes following EDD administration.
Results
Initial analysis of hormone levels revealed no significant change in testosterone after 1 week of treatment. However, a significant decrease in testosterone was noted after 6 and 12 weeks with all 3 drugs (P<0.05).
| Week 1 | Week 6 | Week 12 | |
| Control | 9.46 | 9.55 | 9.49 |
| Sildenafil | 9.00 | 8.63 | 8.45 |
| Tadalafil | 9.10 | 8.67 | 8.39 |
| Vardenafil | 8.91 | 8.78 | 8.18 |
At the same time, a moderate (non-significant) decrease in estradiol and progesterone levels was seen in all 3 drugs.
These changes correlated with a significant decrease in steroidogenesis (17β-hydroxysteroid dehydrogenase, 17-ketosteroid reductases) and related protein expression (CYP11A1, CYP 19C).
| 17β-hydroxysteroid dehydrogenase | 17-ketosteroid reductases | |
| Control | 0.15 | 1.67 |
| Sildenafil | 0.10 | 1.38 |
| Tadalafil | 0.07 | 1.30 |
| Vardenafil | 0.05 | 1.18 |
| (unit/min/mg protein) | (unit/min/mg protein) |
Likewise, all levels of antioxidant enzymes were significantly decreased, except for glutathione S-transferase (GSTs) in the Tadalafil group.
| GST | GPX | SOD | CAT | |
| Control | 0.80 | 78.6 | 3.28 | 1.81 |
| Sildenafil | 0.64 | 67.2 | 4.10 | 2.35 |
| Tadalafil | 0.74 | 65.4 | 3.68 | 2.46 |
| Vardenafil | 0.50 | 69.4 | 4.41 | 2.32 |
| (U/mg protein) | (U/mg protein) | (U/mg protein) | (H2O2/mg protein/min) |
Similarly, analysis of free radicals (MDA / TBARS), reduced glutathione (GSH) and glutathione reductase enzyme (GR) in the testes revealed significantly reduced levels with all 3 drugs.
| TBARS | GSH | GR | |
| Control | 2.01 | 1.66 | 82.43 |
| Sildenafil | 1.29 | 0.96 | 59.95 |
| Tadalafil | 1.18 | 1.00 | 57.80 |
| Vardenafil | 1.00 | 1.05 | 41.55 |
| (µmol/g tissue) | (µmol/g tissue) | (µmol/min/mg protein) |
Finally, histopathological examination of testicular tissue revealed that the Sildenafil, Vardenafil and Tadalafil groups confirmed a statistically significant decrease in spermatocytes and number of sperms.
Limitations
- Human and mice spermatogenesis is similar but not identical.
Funding
No external funding was declared for this study.
Glossary
Histopathological
The study of the structure of cells and tissue under a microscope.
Spermatocyte
A male cell which undergoes meiosis forming spermatids.
Steroidogenesis
A biosynthetic process by which cholesterol is converted into steriods.
Oxidative stress
An imbalance between reactive oxygen species (free radicals) and antioxidants in the body.
Similar studies
Pentyala S, et al. (2011). Pharmacokinetic drug interactions of phosphodiesterase-5 inhibitors mediated by cytochrome P450 3A4 isoform. https://doi.org/10.5897/IJMMS.9000173
Jarvi K, et al. (2007). Daily Vardenafil for 6 Months Has No Detrimental Effects on Semen Characteristics or Reproductive Hormones in Men With Normal Baseline Levels. https://doi.org/10.1016/j.juro.2007.10.077
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