Impact of Viagra, Cialis and Vardenafil on Male Fertility

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Impact of Viagra, Cialis and Vardenafil on Male Fertility

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

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 1Week 6Week 12
Control9.469.559.49
Sildenafil9.008.638.45
Tadalafil9.108.678.39
Vardenafil8.918.788.18
Change in the plasma levels of testosterone of male rabbits following 12 weeks of EDD treatment.

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
Control0.151.67
Sildenafil0.101.38
Tadalafil0.071.30
Vardenafil0.051.18
(unit/min/mg protein)(unit/min/mg protein)
Change in the activity of 17β-hydroxysteroid dehydrogenase and 17-ketosteroid reductases of male rabbits after 12 weeks of EDD treatment.

Likewise, all levels of antioxidant enzymes were significantly decreased, except for glutathione S-transferase (GSTs) in the Tadalafil group.

GSTGPXSODCAT
Control0.8078.63.281.81
Sildenafil0.6467.24.102.35
Tadalafil0.7465.43.682.46
Vardenafil0.5069.44.412.32
(U/mg protein)(U/mg protein)(U/mg protein)(H2O2/mg protein/min)
Change in the activity of glutathione S-transferase (GST), glutathione peroxidase enzyme (GPX), superoxide dismutase enzyme (SOD) and catalase (CAT) of male rabbits after 12 weeks of EDD treatment.

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.

TBARSGSHGR
Control2.011.6682.43
Sildenafil1.290.9659.95
Tadalafil1.181.0057.80
Vardenafil1.001.0541.55
(µmol/g tissue)(µmol/g tissue)(µmol/min/mg protein)
Change in thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and glutathione reductase enzyme (GR) of male rabbits after 12 weeks of EDD treatment.

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

  1. 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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