(For those that don’t know, sildenafil/PDE5 inhibitor = viagra).
medscape.com/viewarticle/520281
If you can’t access the above link, try this scholar.google.com/scholar?q=pro … rt=10&sa=N … and scroll down to #5 on the page.
Sexual Dysfunction After Radical Prostatectomy: Recent Studies CME
Disclosures
John P. Mulhall, MD
Even in its nerve-sparing form, radical prostatectomy (RP) is associated with a number of sexual dysfunctions including erectile dysfunction (ED), anejaculation, orgasm-associated incontinence (climacturia), Peyronie’s disease, and penile length changes. The presence of 1 or more of these conditions is often associated with significant reductions in the quality of life of the patient and his partner.
It is well established that 2 major patient populations with high risk of ED have a reduced ability to respond to PDE5 inhibitors: men with diabetes and men who have undergone radical prostatectomy. Bennett and colleagues[1] reported the results of an uncontrolled study on the effectiveness of sildenafil after RP.
In 187 patients who had functioning erections before surgery (average patient age was 58 years) statistical analysis demonstrated significant improvement in sildenafil response over the first 18 months after radical prostatectomy. At 18 months post-RP, 52% of men had functioning erections, and significant predictors of failure to respond to sildenafil post-RP were older age (patients ≥ 60 years), having more than 2 vascular comorbidities (diabetes, hypertension, dyslipidemia, cigarette smoking), early stage after surgery (≤ 6 months). The major take-home message from this paper was that patients who fail sildenafil early after RP should be re-challenged on a regular basis after surgery as the time to optimal response appears to be more than 18 months after surgery.
Nelson and coworkers[2] assessed predictors of sexual satisfaction in men with prostate cancer. In a database of 352 men with early and late-stage prostate cancer, satisfaction and erectile function were assessed by questionnaire. Patients were also questioned regarding anxiety and depression. The average patient age was 67 years old. Older patient age and the presence of depression and anxiety were associated with a significant reduction in satisfaction while good erectile function was associated with higher levels of satisfaction. Of all predictive factors, erectile function was identified as the strongest predictor.
There is accumulating evidence that the presence of blood flow abnormalities in the penis after RP is a predictor of long-term ED after radical prostatectomy. Ohebshalom and colleagues[3] analyzed the significance of post-RP penile blood flow in the prediction of long-term erection function.
The study involved assessment of men after RP who had penile blood flow measured (by Doppler penile ultrasound) within 6 months of surgery. All men had functioning erections preoperatively based on self-report. There were a total of 111 patients, with an average age of 57 years. Twenty-nine percent of patients were found to have normal postoperative penile blood flow, while 71% had abnormal penile blood flow. Fifteen percent were found to have a component of venous leak, a significant predictor of failure to obtain functioning erections after RP with or without PDE5 inhibitors.
There were significant differences between those men with normal and abnormal penile blood flow in erection function scores, erection hardness, and percent of patients responding to sildenafil after RP. These data support the accumulating evidence that blood flow changes that occur at the time of surgery or early after RP are predictive of erection function recovery.
Much has been written about the topic of penile rehabilitation after RP. Post-RP rehabilitation has taken numerous forms, including the use of chronic PDE5 inhibitors, intracavernosal injections, vacuum device therapy, or a combination of all of the above. Wang and colleagues[4] presented data on the compliance of patients in a formal rehabilitation program.
This study was conducted as part of larger trial on the effectiveness of unilateral cavernous grafting at the time of RP. Penile rehabilitation was initiated 6 weeks postoperatively with a vacuum erection device (VED), intracavernosal injection (ICI), and the use of sildenafil. Compliance was evaluated by assessing the number of times/week that VED or ICI was performed. A total of 100 patients were enrolled in the study. At 4, 8, and 12 months after RP, 73%, 67%, and 47%, respectively, of patients were continuing to comply with vacuum therapy; at 4, 8, and 12 months after RP, 52%, 26%, and 35% continued to use injections. In this study, older patients were more compliant than younger ones. These data indicate that even in a formally structured rehabilitation program, patients drop out as time passes.
RP may be associated with loss of penile length and volume. Huber and coworkers[5] reported on penile length after RP. As part of a larger study assessing the effectiveness of cavernous nerve grafting, a total of 65 men had penile rehabilitation initiated 6 weeks postoperatively consisting of daily use of the VED, biweekly ICI, and patient-directed use of sildenafil. Penile length was measured preoperatively, at 6 weeks, and every 4 months up to 2 years after surgery.
Of the 39 patients reported on in this interim analysis, 25 received unilateral sural nerve grafting and unilateral nerve-sparing prostatectomy while 14 patients received a unilateral nerve-sparing prostatectomy alone. Patients who had return of erectile function had a significant preservation of penile length at 12 months compared to 6 weeks postoperatively. At 12 months, the mean improvement in penile length from the 6-week measurement for patients who were potent was 1.2 cm. Patients who had not regained erectile function showed an increase of only 0.2 cm. The difference between these 2 groups was statistically significant.
Orgasm-associated incontinence, also termed climacturia, has been receiving increasing attention in the medical literature. It can have a significantly negative impact on a man’s and his partner’s sexual satisfaction. Abouassaly and coworkers[6] reported their findings with men who had climacturia after having undergone RP. Of an estimated 220 patients evaluated, 26 men experienced urine leak almost exclusively at the time of orgasm. The average age of the patients was 62 years. There was no clear association with degree of nerve sparing or daytime continence level. Patients experienced anywhere from 3 to 120 mL of urine leak (by patient self-report) at the time of orgasm. The authors feel that the occurrence of ejaculatory incontinence high enough for it to be considered as part of the routine post-prostatectomy evaluation.
The results from studies using animal models to assess the use of drugs for erection nerve protection were presented. Minor and colleagues[7] from the University of California-San Francisco presented their data on a novel compound called FK1706 (a derivative of the available drug, FK506 currently in trials for this indication). This drug is different from FK506 in not being an immunosuppressant.
FK1706 facilitated erection recovery with penile pressures 4 times higher in the high-dose FK treatment group compared to the group without the use of FK1706. Kendirci and coworkers[8] evaluated the compound Ino-1001 as a protectant of erection nerves.
They demonstrated that animals treated with the compound had a significant increase in erection function compared to those not treated. Lehrfeld and colleagues[9] looked at the combination of sildenafil and FK506 in rats that underwent nerve crush injury. A course of combined sildenafil and FK506 treatment after cavernosal nerve injury had the maximum positive effect on erectile function recovery. However, sildenafil alone also appeared to exert a protective effect on erectile function.
References
Bennett N, Parker M, Donohue J, Mulhall J. Sildenafil following radical prostatectomy: chronology and predictors of response. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 11.
Nelson C, Roth A, Mulhall J. Correlates of sexual satisfaction in men with prostate cancer. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 113.
Ohebshalom M, Mulhall J, Flanigan R, Waters W, Parker M. Erectile hemodynamic status following radical prostatectomy correlates with erectile function outcomes. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 117.
Wang R, Huber N, Madsen L, Wood C, Babaian R. Long term compliance to penile rehabilitation program following radical prostatectomy. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 156.
Huber N, Wood C, Babaian R, et al. Recovering penile length and erectile function following radical prostatectomy. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 60.
Abouassaly R, Lane B. Lakin M, Klein E, Gill I. Ejaculatory incontinence after radical prostatectomy: a review of 26 cases. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 1.
Minor T, Bella A, Carrion R, Price R, Lue T. The effect of FK1706 on erectile function following a bilateral cavernous nerve crush injury in a rat model. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 10.
Kendirci M, Zsengellér Z, Szabo C, Hellstrom W. Cavernosal neuroprotection with Ino-1001 in a rat model of postprostatectomy erectile dysfunction. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 70.
Lehrfeld T, Lagoda G, Burnett A. An early course of sildenafil and FK506 treatment on erectile function after cavernous nerve injury. Program and abstracts of the Sexual Medicine Society of North America Fall Meeting; November 17-20, 2005; New York, NY. Abstract 85.