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Monday, August 20, 2007

ED After Prostatectomy - Part 1. Introduction

[Updated August 19, 2008]

Parts in the Series


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

Background


The reader is encouraged to review the following prior to reading this post:
The PCRI and Phoenix5 glossaries may be useful to consult while reading some of this material. How long it takes to recover (together with pointers to illustrative graphs) is discussed under Nerve Damage in the Mechanisms Behind ED section below.

Causes


ED is associated with a number of prostate cancer-related phenomena:
  • Prostatectomy. Orgasm, ejaculation and erection are independent physical functions. (1) Orgasm. In nearly all cases orgasm continues to possible after prostatectomy although possibly at a reduced level. (2) Ejaculation. The prostate provides ejaculate so with no prostate ejaculation is not possible (although a small amount of fluid from the Cowper's Gland [PMID: 15811067][full text] may still be emitted). (3) Erection. There are two nerve bundles that control erections that lie in close proximity to the prostate. If they are not diseased then they can both be spared (double nerve sparing) in which case erection will likely be possible again, particularly for younger men and with good surgical technique; however, even in that case the nerve bundles are so delicate and so close to the prostate that they will almost certainly sustain some damage. Nerves take a long time to heal and it may take as long as a year or two to recover the ability to have erections and even then they may be at reduced hardness. If one nerve bundle is diseased and therefore removed the recovery of erections is less probable but may still be possible in some cases. If both nerve bundles are diseased and therefore removed then erections will not be possible. A January 2008 paper also suggests that the arteries to the nerve bundles need to be preserved for optimum functionality, not just nerve bundles: [PMID: 18221962].
  • Post-Prostatectomy. It is often not realized that the damage that occurs as a result of prostatectomy occurs not only during the surgery but in the weeks afterwards. Inability to have an errection in the post surgical period can result in lack of oxygen to the penis which may cause further damage during this time. Attention to rehabilitation can minimize this damage.
  • Biopsy. The prostate biopsy relationship is discussed by Sallami S, Saaj IB, Chliff M, et al. Did prostate biopsy and repeated prostate biopsies affect erectile function? Program and abstracts of the American Urological Association 2007 Annual Meeting; May 19-24, 2007; Anaheim, California. Abstract 784. They speculate that the degredation of sexual function after prostate biopsies may be due to "direct injury to the ejaculatory ducts, periejaculatory duct fibrosis, or most likely inflammation".
  • Psychological. Depression resulting in ED can arise from the diagnosis of cancer which can be traumatic. Also a dynamic can be set up "where intercourse is impossible after surgery, and a pattern of avoidance begins, with the man withdrawing sexually and his partner reluctant to discuss the issue for fear of upsetting him further. He interprets this as lack of interest, which exacerbates his feelings of inadequacy, and the couple settle into a non-sexual relationship." [link]
  • Prostate Cancer. If left untreated prostate cancer, itself, can cause ED.

Factors Affecting ED After RP


The following factors are known to affect the course and extent of ED after RP:

Preoperative
  • patient age
  • preoperative sexual function
  • psychological adjustment to cancer diagnosis
  • co-existing medical diseases (diabetes, hypertension, coronary artery disease, dyslipidemia)
  • disease stage
  • pre-existing urinary incontinence
  • adjuvant treatments (hormone, radiation)
  • smoking status
  • motivated partner
Intraoperative
  • surgical technique and experience. e.g. [PMID: 17626532], [PMID: 17196737], [PMID: 18261153], [PMID: 15538237], [PMID: 10799186] (Note that recovery rates which are not stratified by risk levels are less meaningful since one can get better results simply by operating only on healthier patients even without any improvement in technique. Also, as discussed elsewhere on the page, percentages can vary hugely simply by changing the definition of potency.)
  • preservation of neurovascular bundles (single nerve sparing, double nerve sparing or no nerve sparing). See Figure 2 of [Lepor, 2005] for an algorithm on deciding on nerve sparing.
Postoperative
  • rehabilitation treatment (when started, methods used)
  • definition of ED.
Comments on the factors:
  • Definition. "The NIH consensus conference definition of ED is the consistent inability to obtain or maintain an erection sufficient for satisfactory sexual relations"; however, some studies interpret that as allowing "the use of medication" and some ignore or re-interpret "consistently". [link]. Objective validated (though possibly imperfect [PMID: 18336609]) measures of ED include the 15 question IIEF questionaire, the abbreviated 5 question IIEF-5 (also known as the SHIM score) or the Sexual Encounter Profile question 2 (SEP2) and question 3 (SEP3). [link] discusses the correlation between IIEF-5 (SHIM) and the full IIEF. The web site of Henry Ford Health Systems has some radar graphs employing SHIM scores to compare outcomes here. A purely psychological test, The Fugl-Meyer's Life Satisfaction Checklist (LISAT-8), and even just questions 2+3+5 on it have been shown to correlate well with the IIEF and SHIM score and can be used as screening tools. (See [PMID: 18042219].) Other instruments exist as well. The percentage of men regaining sexual functionality varies widely depending on exactly what definition is used as pointed out in this January 15, 2008 New York Times article.

  • Robotic vs. Open Surgery. Robotic surgery is claimed to have improved ED profile over open surgery by 78% of sites surveyed; however, only 2 actually provided the data to back this up and Rojas-Cruz C, Mulhall JP. conclude that such claims are unproven. Program and abstracts of the American Urological Association 2007 Annual Meeting; May 19-24, 2007; Anaheim, California. Abstract 1034. [link]

  • Reference. Many of the above factors are mentioned in: [PMID: 7523730] as quoted in Zippe et al.

  • Results. The fraction of men regaining sexual function varies widely based on specific factors. 80% of men under 55 years old with double nerve sparing regained erectile function while no one over 55 with zero or one neurovascular bundle preserved regained it. [PMID: 1101862] When viewing these results its important to compare this to a baseline of the prevalence in the wider population of men without prostate cancer where 50.1% of men without prostate cancer have at least mild ED and 21.7% have severe ED. (This is based on 1273 men aged 40-56 years reported at the 2007 AUA meeting by Walts J, Salomon G, Perrotte P, et al. in their presentation "Prevalence of erectile dysfunction in a prostate cancer screening population" Abstract 1035 and discussed [here].)

Mechanisms Behind ED


  • Nerve Damage. Nerve impulses activate a series of physiological processes which culminate in an erection. Due to the position of the erectile nerves near the prostate it is difficult not to damage them somewhat during the surgical process. They are quite delicate and even if they are not obviously injured neurapraxia (twisting, compressing or stretching of the nerves) may be sufficient to cause harm. If the nerves are not removed self repair, to the extent possible, can take as much as two years. See Figure 2 in [link] or [link]. These charts show that the proportion of men recovering full erections increases in an approximately linear fashion over the first year with 37% successful by year end and 62% by the end of year 2 with only a slight further increase by year 3. Neurological damage is discussed in this review by Dean & Lue, 2005.

  • Vascular. The nerve impulses trigger activation of nitric oxide, NO (conveniently referred to simply as oxygen though not strictly correct), with a subsequent chemical reaction. (The 1998 Nobel Prize in Medicine was given for the discovery of NO as a significant physiological process.) The chemical reaction (see [link] for a slightly more detailed description) that follows initiation of the nerve impulses and NO activity culminates in the relaxation of smooth muscule (SM) fiber in the penis causing it to fill with blood from the arteries. Such expansion also compresses the outgoing veins which blocks them so that the blood is trapped within the penis maintaining the erection. While the nerves heal the absence of any trigger from the nerves starves the penis of NO inducing fibrosis (i.e. build up scar tissue and collagen) which may make the situation worse. Such fibrosis can result in (1) insufficiency, i.e. insufficient arterial blood flowing into the penis and/or (2) venous leak, i.e. interference with the cutoff of outflowing blood through the veins so the blood is not trapped within the penis thwarting the erection process. Such fibrosis takes at least a few weeks to occur after surgery and catheter removal so steps to promote blood flow and oxygenation to the erectile tissue should not be left longer. In the absence of such action damage can occur in the weeks following surgery. Such damage may make the subsequent treatment of ED more difficult and even result in irreversable harm occuring in this post surgical period. Also, by taking steps without excessive delay progress will be seen sooner which may lessen adverse psychological reactions. Penile vascular status can be measured with Doppler ultrasonography (DUS) and such status has been correlated with subsequent erectile function [PMID: 18694409].

  • Psychological. The patient's reaction to the diagnosis of cancer and possible depression may be a contributing effect. See the comments in the Causes section above about the dysfunctional relationship dynamics that can set in.
There are other potential causes of ED, as well, but those not normally associated with prostatectomy.

In the next part of this series rehabilitation treatment for ED will be discussed. Click on next below.

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

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