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Tuesday, August 28, 2007

ED After Prostatectomy - Part 2. Rehabilitation

[updated June 16, 2010]

Parts in the Series


ED After Prostatectomy - Part 1. Introduction (previous)
ED After Prostatectomy - Part 2. Rehabilitation (current)

The reader should be sure to have read Part 1 of this series as it gives useful background needed for reading this Part. A review of rehabilitation is given in this Feb. 2009 paper in the Canadian Urological Association Journal: [PMID: 19293974] [Full Text] .

Fibrosis and oxygenation

As discussed in Part 1, the damage that is done can occur not only during the surgery but in the period of time after the surgery due to a build up of fibrosis in the penis blocking nitric oxide (NO) and so erections. Such fibrosis can represent irreversable damage. By achieving erections as soon as possible after catheter removal (within 6-8 weeks), oxygenation will occur and fibrosis may be prevented. In [Endotext] this is referred to as "avoidance of penile hypoxia through regular tissue oxygenation via erections".

Treatment

Although it does not appear to have been specifically studied, the various treatments are not mutually exclusive so simultaneous modalities may be considered, e.g. exercise + drugs + VED

This article by Sidney Radomski is only one page and summarizes what works and what does not work: [link]. Readers are encouraged to read it before reading on.

Other sources of information include the Phoenix5 site [link] and a 25 page article outlining various treatments by Drs. Stephen Auerbach and Aubrey Pilgrim [here].

Exercise

Exercise consists of attempting to achieve erections possibly with the aid of any of the following treatments. "The use of at least one aid was an independent predictor of more favorable sexual HRQOL" (higher quality of life). [PMID: 16844457].

Frank Sommer, a German urologist, has a set of exercises which he claims are just as effective as Viagra (though they do not appear to have been specifically tested post prostatectomy): See [men-and-health] and [urotoday] for information on the study. The first link in the last sentence also provides a description of Sommers' exercises. Note that Sommers' exercises are different than the incontinence exercises discussed in [this post].

There may be a benefit of exercise prior to surgery as well although we have not found a source where it was clearly established.

Pelvic floor or Kegel exercises have also found to be beneficial. See [PMID: 15527607]
[Full Text] and particularly Box 1 of that paper where the exercises are described.

Dr. Dorey has some materials on exercise for erectile dysfunction [Dorey site] which are reviewed [here].

PDE-5 Inhibitors

Viagra (sildenafil), Levitra (vardenafil) and Cialis (taladafil) are drugs which inhibit PDE-5 which breaks down the key promoter of erections, cGMP. This indirectly enhances and prolongs erections provided one can achieve at least partial erections already.

Daily Administration. It can work in conjunction with appropriate exercise to achieve more effective erections which may enhance the rehabilitation process. For rehabilitation purposes these drugs are taken at a low dosage every other day or other frequency although some good results have been reported by taking them every day. This [PMID: 16766116] discusses a successful trial of daily administration of Cialis and the review article in the following link discusses various good results in using PDE-5 inhibitors on a daily basis rather than on demand for ED, cariovascular problems and other problems: [PMID:1746047]. Table 1 of this last paper summarized the Benefits and Limitations of daily administration for ED as follows. Benefits: salvage of on-demand responders, improved treatment response in difficult-to-treat groups, disease modification, may approximate more natural sexual function, randomized placebo-controlled trials demonstrate efficacy and safety for ED of various etiologies. Limitations: extended term follow-up limited -- safety and efficacy profiles require further elucidation, mechanisms of treatment effects incompletely understood, disease modification -- attractive concept but evidence-based data limited, patient cost, no evidence of tachyphylaxis to date but longer follow-up needed. (Tachyphylaxis refers to decreased response after initial administration requiring drug-free periods.) A 2008 paper in the Journal of Urology found that patients who had better pretreatment sexual function responded better to PDE-5 inhibitors. [PMID: 18206926].

Mulhall's Approach. In a Medscape article [Penile Rehabilitation Following Radical Prostatectomy] (see section entitled Structure of Rehabilitation) and 2006 Urology Times interview John Mulhall (papers) indicates that there is animal evidence for daily administration (every other day for Cialis) preoperatively as well as post operatively and so uses the following protocol for his patients (quote is from Medscape link):
I encourage presurgical patients to use low-dose PDE-5 inhibitors on a nightly basis for 2 weeks before their operation. This strategy is based on the animal data supporting pretreatment. These patients are then told that with the catheter in place they should continue to use low-dose PDE-5 inhibitors on a regular basis (sildenafil and vardenafil nightly, tadalafil 3 times a week). When they are given the go-ahead to resume attempts at obtaining erections, they are switched to a low-dose PDE-5 inhibitor 6 nights a week and a maximum dose 1 night a week. The maximum-dose pill needs to be used in an appropriate fashion with sexual stimulation. The patients are encouraged to return to the office 6 weeks after surgery, which will allow them approximately 4 weeks to try maximum-dose medication.
After 6 weeks the protocol is as follows. In the exceptional case that this is successful in restoring sexual function within 6 weeks, they can continue with PDE-5 inhibitors. In the more likely case that they are not successful within 6 weeks then therapy is switched to intracavenosal penile injections twice a week (with appropriate training) and low dose PDE-5 inhibitors on non-injection nights. Because of its longer half life Cialis is not appropriate for this phase of the therapy. After a year they try maximum PDE-5 dosage once a month and if successful on that can stop injections. He normally expects some improvement within 10-14 months and optimal functionality in 18 to 24 months and notes that failure to respond to PDE-5 inhibitors in the first year does not necessarily preclude an excellent response after two years. The link cited above also gives a variation of this protocol in the case that it is started post-operatively. John Mulhall has recently written a patient-oriented book.

Comparison. A key difference among the drugs is that the half lives of Viagra, Levitra and Cialis are such that they last 2-8 hours, 4-8 hours and 24-36 hours respectively. The longer lasting Cialis would appear to be superior from the viewpoint of rehabilitation and also can be used at the lowest concentration which may make side effects less likely. However, there have been claims that Viagra is more effective at achieving intracellular drug concentration and cGMP accumulation as well as one study that claims that Levitra results in higher concentration [PMID: 15213306]. Others have indicated that there is individual variation and if one of the three drugs does not work to try the others. Such individual variation might also be expected based on the fact that the three drugs can act on different receptors. Detailed comparisons of the three are in the table at the bottom of page 2 in this link Greenspan, 2004 and Table 1 of Mehrotra, 2007. A February 2008 study concluded that patients who were given a chance to try all three and choose for themselves had better compliance with taking this medication [PMID: 18086159]. For side effects, contraindications and more information see: www.viagra.com, www.levitra.com and www.cialis.com . A new PDE-5 inhibitor is udenafil. See [PMID: 18221288].
A November 2007 review of PDE-5 inhibitors by Carson can be found here: [PMID: 17983891] [Full Text] also mentions that coffee is a PDE-5 inhibitor; however, coffee may have an adverse affect on incontinence and its pro-inflammatory properties might also promote recurrence.

(As an aside we mention that PDE-5 inhibitors may have benefits against hypertension and other vascular diseases and are also believed to enhance one's ability to work in a low oxygen atmosphere such as would be experienced on mountain tops or by pilots.)

Injections

Although these drugs are desirable from the viewpoint of not being invasive, because they do not generate erections but simply block inhibitors they may not be as effective in the earlier stages of recovery as injections into the penis which directly generate the nitric oxide (NO) needed to begin the chemical process that leads to erections.

According to [PMID: 16158022] 55% of prostate cancer patients treated with prostaglandin E1 injections felt that their sex life improved.

More information on injections can be found at the Phoenix5 site [link]

Vacuum Erection Devices

Vacuum erection devices (VED) are mechanical devices that use suction to draw blood into the penis resulting in an erection. They are effective although one gets a cold erection and can be a nuisance. A ring is used to prevent the blood from escaping; however, simply for the purpose of achieving erection it would be good enough to pump up without the ring on a regular basis. There is some debate on whether or not VEDs provide oxygenation or not. An instructional video showing how these vacuum devices work can be found [here] and comments by users are found [here].

VEDs can also be used for rehabilition. In [PMID: 17822466] investigators perform a randomized control trial which concludes that daily use of a VED starting one month after prostatectomy signficantly "improves early sexual function and helps to preserve penile length". The following earlier work also supported the fact that early VED use can preserve penile length [PMID: 17657210].

If one can achieve erections it may be possible to prolong them simply by using a silicon ring. This is inexpensive and easier to use than a VED plus a ring. A testimonial on its effectiveness is found here: [link]. The ring itself is unlikely to provide oxygenation and might even interfere with oxygenation if left on too long so its only use would be to allow sexual activity.

Other treatments. Other treatments are discussed at the Phoenix5 site [link] and new treatments on the horizon are discussed on page 4 of the August 2005 PC Insights newsletter [link].

ED After Prostatectomy - Part 1. Introduction (previous)
ED After Prostatectomy - Part 2. Rehabilitation (current)

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