Indian Journal of Urology
UROSCAN
Year
: 2011  |  Volume : 27  |  Issue : 4  |  Page : 567--568

Phosphodiesterase-5 inhibitors: Is it the answer to all male sexual and urinary problems?


Neeraj Kumar Goyal 
 ,

Correspondence Address:
Neeraj Kumar Goyal
,




How to cite this article:
Goyal NK. Phosphodiesterase-5 inhibitors: Is it the answer to all male sexual and urinary problems?.Indian J Urol 2011;27:567-568


How to cite this URL:
Goyal NK. Phosphodiesterase-5 inhibitors: Is it the answer to all male sexual and urinary problems?. Indian J Urol [serial online] 2011 [cited 2022 Jan 25 ];27:567-568
Available from: https://www.indianjurol.com/text.asp?2011/27/4/567/91462


Full Text

 Summary



This study was a prospective randomized controlled study to determine the effects of phosphodiesterase-5 inhibitors (PDE5-I) on Leydig cell secretory function (LCSF) and various seminal parameters in infertile men. [1] Seventy-five men with oligoasthenospermia were included in the study and divided into four groups. Before starting the treatment, two consecutive semen analyses were performed at a gap of 3 days. The mean value for each semen parameter was then calculated from these two samples. Peripheral serum levels of follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and insulin-like-3-peptide (INSL3) were evaluated similarly in all the patients before starting the treatment. Participants were divided into four groups. Vardenafil (10 mg/day), sildenafil (50 mg/day) or L-carnitine (1000 mg/day, i.e. positive controls) was administered, respectively, to 23 (group A), 25 (group B) and 26 (group C) infertile patients for 12 weeks. Group D patients (n=22) received no treatment and served as a negative control to evaluate the influence of time on various serum and semen parameters. Two semen analyses were repeated after 12 weeks of study period and the mean value of each semen parameter was calculated again. Similarly, peripheral serum levels of FSH, LH, testosterone and INSL3 were evaluated after the treatment. At the beginning of the study, there was no significant difference in the four groups regarding any of the semen or serum parameters under study.

After the treatment period, the mean values of sperm count (SC) (million/mL), %motile spermatozoa (%MS) and percentage morphologically normal spermatozoa (%MNS) were significantly greater in groups A and B than before. In contrast, the improvement in these seminal parameters was not significant in groups C and D. Similarly, in groups A and B, the peripheral serum mean INSL3 concentration was significantly greater after treatment than that before, in contrast to groups C and D. The proportion of men with a positive effect on SC, i.e. an increase of ≥50% of the baseline value, was significantly greater in groups A and B than in groups C and D.

 Comments



Etiological treatment of male infertility is not possible in many patients as the cause of various seminal abnormalities often goes undiscovered. Therefore, there is a need to discover safe and effective pharmaceutical agents for treating idiopathic male infertility. Current evidence-based medicine does not support any specific agent for managing idiopathic male infertility. Pharmaceutical agents that stimulate LCSF might be anticipated to enhance spermatogenesis in subpopulations of infertile men.

In experimental studies, PDE5 has been shown to be expressed in Leydig and peritubular cells in adult rat testis. This observation supports the idea that cGMP might influence these two cells, i.e. the testosterone synthesis by Leydig cells and the transfer of spermatozoa by the relaxation of peritubular lamina propria cells. [2]

PDE5 inhibitors are the first-line treatment for the management of erectile dysfunction, and are effective for both organic and psychogenic impotence. The present study is the first to show that vardenafil and sildenafil enhance LCSF in oligoasthenospermic infertile men, evident by the significantly larger serum INSL3 profiles after administration of these agents. INSL3 is a peptide with a role in the first phase of testicular descent, and is a marker of LCSF. [3] An increase in LCSF probably explains the significantly higher mean SC and %MS after PDE5-I treatment, as optimal LCSF is of paramount importance for maintaining normal spermatogenesis. Apart from this, intraepididymal testosterone profiles that are important for the epididymal sperm maturation and development depend on the LCSF.

The increase in LCSF after treatment might stimulate Sertoli cell secretory function also as Sertoli cell secretory function is androgen-dependent. This in turn would provide a more optimal biochemical environment within the seminiferous tubules, stimulating spermatogenesis in oligoasthenospermic men. PDE5-I has been suggested to enhance prostatic secretory function and improve sperm motility. Apart from this, sildenafil treatment reduces the overall stress levels thus inducing a more complete ejaculation and, subsequently, more good-quality spermatozoa in the semen. [4]

Various PDE isoenzymes have been localized in different zones of the human prostate. This finding has lead to widespread research on the use of these agents for alleviating lower urinary tract syndromes (LUTS) in men. Long-term efficacy and safety of tadalafil has been proven for its use in LUTS secondary to benign prostatic hypertrophy (BPH). [5] Considering all these facts, and its effectiveness in different conditions, one may not be wrong in saying that this single pill is the answer to all male sexual and urinary problems.

References

1Dimitriadis F, Tsambalas S, Tsounapi P, Kawamura H, Vlachopoulou E, Haliasos N, et al. Effects of phosphodiesterase-5 inhibitors on Leydig cell secretory function in oligoasthenospermic infertile men: A randomized trial. BJU Int 2010;106:1181-5.
2Scipioni A, Stefanini S, Santone R, Giorgi M. Immunohistochemical localisation of PDE5 in Leydig and myoid cells of prepubertal and adult rat testis. Histochem Cell Biol 2005;124:401-7.
3Bay K, Hartung S, Ivell R, Schumacher M, Jürgensen D, Jorgensen N, et al. Insulin like factor 3 serum levels in 135 normal men and 85 men with testicular disorders: Relationship to the luteinizing hormone-testosterone axis. J Clin Endocrinol Metab 2005;90:3410-8.
4Jannini EA, Lombardo F, Salacone P, Gandini L, Lenzi A. Treatment of sexual dysfunctions secondary to male infertility with sildenafil citrate. Fertil Steril 2004;81:705-7.
5Donatucci CF, Brock GB, Goldfischer ER, Pommerville PJ, Elion-Mboussa A, Kissel JD, et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A 1-year, open-label extension study. BJU Int 2011;107:1110-6.