The preservation of NANC nerve fibers (producing nitric oxide, NO) is necessary for erection recovery after retropubic radical prostatectomy (RRP). Yet, it is impossible to establish when and if a patient will recover erections; therefore, we investigate the prognostic value of cavernous blood NO levels on this parameter. Nerve-sparing RRP was performed on 14 patients for localized prostate cancer. We evaluated all patients 3 months after surgery by IIEF score: no patients had erections. A cavernous blood sample was also taken to determine NO levels (as nitrite). Patients were evaluated again 18 months after surgery. In six cases, erectile function was compromised, whereas in seven cases, potency was restored. Statistical analysis showed a relationship between nitrite levels in cavernous blood 3 months after surgery and the recovery or erectile function at 18 months. We propose that cavernous NO blood levels are a prognostic index of erection recovery.
Erectile dysfunction often follows radical retropubic prostatectomy (RRP). Previous studies have shown that the recovery of erectile function occurs in 41–69% of subjects in a period ranging from 6 to 18 months, provided that at least one of the neurovascular bundles is preserved.1, 2, 3
Data in the experimental animal have shown that the improvement and the recovery of erectile function is probably due to the regeneration of nerve fibres, particularly those producing nitric oxide (NANC fibres).4, 5, 6 The interruption of NANC fibres, during radical prostatectomy, leads to permanent erectile dysfunction, whereas the preservation of at least one neurovascular bundle permits nerve regeneration and the spontaneous recovery of erectile activity within 6–18 months.4
Nitric oxide (NO) is one of the most important mediators of the complex mechanism involved in erection and it is formed by NO synthase (NOS).7, 8, 9, 10, 11 Three different NOS isoforms (I, II, III) occur in human tissues.5 In bilateral neurological damage, isoform I decreases and isoforms II and III alone are not able to produce the NO levels necessary for achieving erection, unless the nerve pathway is also intact. For this reason, it is extremely important to preserve, at least partially, the neurovascular bundles during surgery not only to ensure proper NOS levels but also, above all, to promote regeneration of the fibres producing NO.
In most patients, it is not possible to establish previously if and when erectile function will be recovered after NS-RRP. Therefore, the aim of our study is to correlate the spontaneous recovery of erectile function 18 months after surgery and cavernous blood NO (nitrite) levels 3 months after surgery, as prognostic value after NS-RRP.
Patients and methods
From January 2002 to January 2003, we performed monolateral or bilateral nerve-sparing RRPs on 14 patients with a mean age of 61 years (range 55–68 years) affected by clinically localized prostate cancer (T1–T2). All patients were evaluated preoperatively from a sexual standpoint, performing a detailed sexual evaluation and using the IIEF questionnaire12 (Question nos. 1–5 and 15).
At 3 months after surgery, the patients were evaluated again by IIEF. During erection induced by prostaglandin intracavernous injection (10 μg of PGE1; Caverject, Pfizer, New York, USA), a blood sample was drawn from the corpus cavernosum to examine nitrite content. All patients were re-evaluated 18 months postoperatively by IIEF and sexual evaluation.
NO is a short-lived radical and spontaneously produces nitrite. For this reason, NO is evaluated as nitrite in the present study.
Plasma was obtained from heparinated blood samples. Aliquots (20–50 μl) of plasma were used for the electrochemical determination of nitrite as described previously.13
Nonparametric test of Mann–Whitney for unpaired data, and Spearman rank correlation coefficient (rho) were performed using SPSS for Windows release 10.0.1 (SPSS Inc., Chicago, IL, USA, 1999). The significance level was set at P<0.05.
Evaluation of patients by IIEF score
All patients showed potency at the preoperative examination, with an average IIEF score12 (Question nos. 1–5 and 15; possible score 0–30) of 27.5.
At the first postoperative follow-up, after 3 months, none of the patients showed spontaneous erections but only tumescence; none of them could have sexual intercourses.
Only 13 patients could be evaluated 18 months after surgery, because one of them had a relapse of the disease. Six patients (40%) presented severe to moderate erectile dysfunction (median IIEF score 6; range 0–13), whereas in seven cases, sexual potency was either entirely or partially restored and patients could have sexual intercourses (median IIEF score 26; range 17–30).
Evaluation of cavernous nitrite 3 months after surgery
Patients could be divided as to their corporal nitrite concentration, into two groups. The median NO (nitrite) of one group was 71 nmol/l (range 30–188 nmol/l), whereas in the other group, it was 608 nmol/l (range 328–800 nmol/l) (Figure 1).
Relationship between IIEF score 18 months after surgery and the cavernous nitrite 3 months after surgery
Statistical analysis showed a close relationship between the degree of erectile function recovery 18 months after surgery and cavernous nitrite levels (rho=0.805; P<0.001), as reported in Figure 1.
Finally, the patient with biochemical relapse of the disease experienced erections before the treatment with androgenic blockage (8 months after surgery). His nitrite levels exceeded 500 nmol/l.
RRP procedure is burdened by two main complications: incontinence and erectile dysfunction. Although many technical modifications have been proposed to achieve a good continence rate (over 95%), this has not occurred for erectile dysfunction.
At the moment, there are no diagnostic or instrumental methods able to predict whether or not a patient will recover erectile function after surgery; in our case study, seven patients (57%) recovered erectile function, but six (43%) did not.
Since our patients had no spontaneous erections 3 months after surgery, we could not use video movies to induce sexual excitement, as previously done by others,16 who found no correlation between erection and NO concentration in cavernous blood. Since erection is a multifactorial phenomenon, the different way of inducing it may justify different results. Moreover, we use surgical patients here and not normal volunteers.
The data presented here indicate that nitrite levels, determined 3 months after surgery in cavernous blood, were lower in the group of patients who did not later recover erectile function. On the contrary, high nitrite values were observed in the patients recovering erectile function 18 months after surgery.
Therefore, cavernous nitrite levels are proposed as a prognostic factor for patients undergoing radical prostatectomy: low nitrite levels could indicate a difficult or unlikely recovery of erectile function, whereas high levels could indicate a good probability of recovery.
Our data suggest that the evaluation of corporal blood nitrite 3 months after surgery can be proposed a prognostic test for the evaluation of penile erection recovery in RRP operated patients.
Walsh PC, Epstein JI, Lowe FC . Potency following radical prostatectomy with wide unilateral excision of the neurovascular bundle. J Urol 1987; 138: 823–827.
Catalona WJ, Basler JW . Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol 1993; 150: 905–907.
Montorsi F, Briganti A, Salonia A, Rigatti P, Burnett AL . Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol 2004; 45: 123–133.
Carrier S, Zvara P, Nunes L, Kour NW, Rehman J, Lue TF . Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat. J Urol 1995; 153: 1722–1727.
Podlasek CA, Gonzalez CM, Zelner DJ, Jiang HB, McKenna KE, McVary KT . Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. Int J Impot Res 2001; 13 (Suppl 5): S1–S15.
Gonzalez-Cadavid NF, Rajfer J . Molecular pathophysiology and gene therapy of aging-related erectile dysfunction. Exp Gerontol 2004; 39: 1705–1712.
Kim N, Azadzoi KM, Goldstein I, Saenz dTI . A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991; 88: 112–118.
Bush PA, Aronson WJ, Buga GM, Rajfer J, Ignarro LJ . Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol 1992; 147: 1650–1655.
Azadzoi KM, Kim N, Brown ML, Goldstein I, Cohen RA, Saenz dT . Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol 1992; 147: 220–225.
Burnett AL . Nitric oxide in the penis: physiology and pathology. J Urol 1997; 157: 320–324.
Burnett AL . Novel nitric oxide signaling mechanisms regulate the erectile response. Int J Impot Res 2004; 16 (Suppl 1): S15–S19.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.
Palmerini CA, Arienti G, Palombari R . Nitrosothiols and S-nitrosohemoglobin. Methods Enzymol 2002; 359: 229–237.
Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE . Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 1993; 90: 8103–8107.
Knowles RG, Moncada S . Nitric oxide synthases in mammals. Biochem J 1994; 298 (Part 2): 249–258.
Moriel EZ, Gonzalez-Cadavid N, Ignarro LJ, Byrns R, Rajfer J . Levels of nitric oxide metabolites do not increase during penile erection. Urology 1993; 42: 551–553.
About this article
Cite this article
Zucchi, A., Arienti, G., Mearini, L. et al. Recovery of sexual function after nerve-sparing radical retropubic prostatectomy: is cavernous nitric oxide level a prognostic index?. Int J Impot Res 18, 198–200 (2006). https://doi.org/10.1038/sj.ijir.3901392
- erectile dysfunction
- nerve-sparing radical retropubic prostatectomy
- nitric oxide