Despite nerve sparing surgery Erectile Dysfunction, ED, constitutes a major problem after radical prostatectomy, RP, (Total Removal of Prostate)
Getting back erection for such a patient is called Penile Rehabilitation Therapy, PRT.
TREATMENT OPTIONS ARE
I
Giving daily medicines is one method of treatment hoping to bring recovery in the damaged smooth muscle tissue.
II
Giving medicine as required before sexual intercourse is another treatment option. Though both these methods, (1) giving medicines daily and (2) giving medicines only before sexual intercourse, not daily have been studied scientifically and debated hugely for the last 10 years, no definite conclusion is arrived about which is the better or correct method to lessen or reverse the damage caused by radical prostatectomy.
What medicines have been used to treat Erectile Dysfunctions following radical prostatectomy?
[1] Oral PDE – 5 inhibitors medicines such as Sildenafil, Vardenafil, Tadalafil
[2] Intracavernous injection of Vaso Active Drugs (drugs like papaverine), ICIVAD.
[3] Intraurethral alprostadil administration MUSE
How was the treatment efficacy measured?
- IIEF-5 validated Questionnaire
- Rigiscan testing
- Nocturnal Penile Tumescence and Rigidity (NPTR) testing
- Percutaneous penile biopsies
-
rat model to test
- penile shaft collagen content
- functional and histologic changes in the penis
Note
While there have been many studies in the rat model showing the benefits of local vasoactive therapies, the crossover to clinical significance in the human has been more difficult to prove.
Ideally the tests should be carried out before and after the surgical procedure.
What is the mechanism of ED that follows RP?
- Primary Neurogenic Damage (Nerve Damage) (despite meticulous nerve sparing surgery)
[3] Klien et al were the first to show (in rat model) nerve damage causes penile apoptosis (atrophy and fibrosis)
[4] In 2003, User and McVary etal demonstrated this. -
Secondary Smooth muscle atrophy is the underlying cause of
- penile atrophy,
- veno-occlusive dysfunction, and
- fibrosis.
First study showing benefit with ICIVAD came in 1997 from F. Montorsi, G. G. Luigi, L. F. Strambi, et al., [1]
By performing percutaneous penile biopsies at the time of RP and 6 months later, Schwartz et al. were the first to demonstrate that early use of 100 mg of sildenafil after RP may preserve intracorporeal smooth muscle content
Mechanism: How PDE – 5 benefit in recovering penile tissue damage?
PDE-5 inhibitors promote penile rehabilitation by stimulating smooth muscle cell replacement via a cGMP mechanism and reducing collagen synthesis via phosphokinase G activation
Which is better regular daily vasoactive medicine or medicine on demand before sexual intercourse?
The benefits of regular daily PDE 5 over before Sexual Intercourse is not confirmed according to abstract presented at 2006 annual meeting [5] of the American Urological Association by the same Dr. Montorsi who in 1997 published first study on benefit of Intracorporal alprostadil Injection.
No significant difference was found in the mean IIEF score between patients treated with daily therapy versus on demand therapy.
[6] A. Bannowsky et al from Germany concluded in 2008 that in cases of early penile erection, daily low-dose sildenafil leads to a significant improvement in the recovery of erectile function.
[7] Montorsi et al recently did the largest randomized, double-blind, double-dummy, multicenter, parallel study done to date. Montorsi et al. recently reported on a vardenafil trial after bilateral nerve-sparing RP that on demand dosing is more effective in improving both erectile function and sexual intercourse completion rates within this patient population prompts reconsideration of the current practice of prescribing nightly PDE 5 inhibitor therapy, as on demand use of vardenafil if equally effective in men with ED following NSRP.
Interesting story
HOW MEDICAL RESEARCH IS DONE?
Medical Research is not a sacrosanct declaration by a God man to be followed without questioning for centuries.
Interestingly powerful arguments have been put forth concluding that damaged penis (chronic hypoxia = continued lack of oxygen and ischemia lack of blood supply) cannot be reversed. Abraham Morgentaler from Harvard University listed several intriguing arguments [8].
WHY CLAIMS OF RESTORING TISSUE DAMAGE BY VASOACTIVE MEDICINES ARE INCORRECT
First, he questioned the theory that penile rehabilitation helps to reverse the chronic hypoxia and ischemia of the flaccid penis following RP.
“But why is there reason to suspect that the flaccid penis is hypoxic, despite having venous oxygen tension? After all, the endothelium of all venous structures suffers no ill effects despite a lifetime of exposure to oxygen levels that are well below those seen in arterial blood.
Second, there is no reason to believe that the penis is ischemic following RP. If it were ischemic, would it not eventually become necrotic?
Furthermore, PDE-5 inhibitors do not increase blood flow to the flaccid penis, so how can benefit occur?”
[9] In a more recent point-counterpoint debate at the 2008 AUA Annual Meeting in Orlando, Fla, Craig Donatucci from Duke University was charged with providing the contrary argument as whether penile rehabilitation was effective after RP.
Craig described the pitfalls of the clinical trials that have been presented thus far.
WE CONCLUDE
with what CRAIG DONATUCCI from Duke University stated in 2008:
“There is not yet enough evidence to declare penile rehabilitation effective; but I am not sufficiently convinced of the ineffectiveness of penile rehabilitation to recommend against it. My opinion is that the benefits of penile rehabilitation are “not proven”; yet it is currently the standard of care”.
[10] This is a review of
Penile Rehabilitation Therapy with PDE-V Inhibitors Following Radical Prostatectomy: Proceed with Caution by
M. Eric Brewer Jr. and Edward D. Kim
REFERENCES
[1]
F. Montorsi, G. G. Luigi, L. F. Strambi, et al., “Recovery of spontaneous erectile function after nervesparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial,”
The Journal of Urology, vol. 158, no. 4, pp. 1408–1410, 1997.
[2]
E. J. Schwartz, P. Wong, and R. J. Graydon, “Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy,”
The Journal of Urology, vol. 171, no. 2, part 1, pp. 771–774, 2004.
[3]
L. T. Klein, M. I. Miller, R. Buttyan, et al., “Apoptosis in the rat penis after penile denervation,” The Journal of Urology, vol. 158, no. 2, pp. 626–630, 1997.
[4]
H. M. User, J. H. Hairston, D. J. Zelner, K. E. McKenna, and K. T. McVary, “Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction,” The Journal of Urology, vol. 169, no. 3, pp. 1175–1179, 2003.
[5]
F. Montorsi, A. Salonia, A. Gallina, et al., “There is no significant difference between on-demand PDE5-I vs PDE5-I as rehabilitative treatment in patients treated by bilateral nerve-sparing radical prostatectomy,” The Journal of Urology, vol. 175, p. S225, 2006.
[6]
A. Bannowsky, H. Schulze, C. van der Horst, S. Hautmann, and K.-P. Jünemann, “Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil,” BJU International, vol. 101, no. 10, pp. 1279–1283, 2008.
[7]
F. Montorsi, G. Brock, J. Lee, et al., “Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy,” European Urology, vol. 54, no. 4, pp. 924–931, 2008.
[8]
J. P. Mulhall and A. Morgentaler, “Penile rehabilitation should become the norm for radical prostatectomy patients,” The Journal of Sexual Medicine, vol. 4, no. 3, pp. 538–543, 2007.
J. P. Mulhall and C. Donatucci, “Is penile rehabilitation effective in improving erectile function after radical prostatectomy? Point-counterpoint debate,” in Proceedings of the American Urological Association Annual Meeting, Orlando, Fla, USA, May 2008.
[10]
Advances in Urology
Volume 2009 (2009), Article ID 852437, 4 pages
doi:10.1155/2009/852437
Review Article
Penile Rehabilitation Therapy with PDE-V Inhibitors Following Radical Prostatectomy: Proceed with Caution
M. Eric Brewer Jr. and Edward D. Kim
Graduate School of Medicine,
The University of Tennessee, Knoxville, TN 37920, USA
Received 19 June 2008; Revised 20 October 2008; Accepted 15 December 2008
Recommended by David F. Penson
Advances in Urology, vol. 2009, Article ID 852437, 4 pages, 2009. doi:10.1155/2009/852437
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