Post-Vasectomy Pain Syndrome

Definition, Incidence, Etiology, Diagnosis, and Treatment Options

Anthony R. Ellis, M.D. and Joseph Scherger, M.D.

Pain and discomfort after vasectomy are a source of concern to prospective vasectomy candidates and the physicians who perform this very effective, permanent, surgical birth control method. There are two broad types of post-vasectomy pain: acute post-surgical pain from the procedure itself, and delayed or chronic pain. The expected acute post-surgical pain frequently causes anxiety for men considering vasectomy. It is generally mild, time limited, and easily managed by non-narcotic analgesia, ice therapy, and rest. The acute post-vasectomy infection or bleeding complications seen in one to six percent of patients (Schwingl PJ, Guess HA, 2000) rarely require subsequent procedural intervention, but may contribute to short-term pain after vasectomy. The nomenclature of delayed or chronic pain after vasectomy has been evolving since it became an area of clinical focus. It has been referred to as post-vasectomy orchialgia (Shapiro EI, Silber SJ, 1979), congestive epididymitis (Schmidt S, 1977), a late post-vasectomy syndrome (Selikowitz SM, Schned AR, 1985), chronic post-vasectomy testicular pain (CPTP) (Ahmed et al, 1997) and post-vasectomy pain syndrome (PVPS) (McCormack and LaPointe, 1988). The latter term seems to have gained some popularity and is widely used, but it is not entirely clear what is being referred to in terms of symptoms, incidence, course, and etiology. Post-vasectomy pain syndrome (PVPS) is usually characterized by chronic or intermittent testicular and/or epididymal pain and is frequently worsened by intercourse or ejaculation. PVPS can be exacerbated by vigorous physical activity, and is frequently accompanied by tender or full epididymides. (Nangia et al, 2000) Symptoms can be unilateral or bilateral and the pain can radiate into the groin or abdomen along the course of the spermatic cord structures.

Definition of PVPS:

There is no formal definition for PVPS and no practical diagnostic criteria exist for PVPS. The nomenclature for chronic genital pain after vasectomy overlap with other diagnostic entities that are not considered vasectomy induced or can occur due to other genital tract injuries or infections. The lack of accepted formal diagnostic criteria for PVPS and symptom overlap with other diagnoses that can cause scrotal pain may hamper effective case finding, delay definitive treatment, and limit therapeutic research. In addition, with a lack of diagnostic consensus and difficulties estimating true incidence, routine inclusion in the pre-operative vasectomy consent process has been delayed and incompletely adopted. Several studies have concluded that a discussion of chronic post-vasectomy testicular pain is imperative and should be included in the informed consent process (Morris et al 2002, Manikandan et al, 2004). The study by Choe and Kirkemo concluded that chronic scrotal pain was the most common post-vasectomy complication that can adversely affect quality of life (Choe and Kirkemo, 1996). Any proposed definition would have to be flexible enough to account for individual differences in presentation, and would include a statement regarding appropriate diagnostic testing and examination excluding other causes for the pain.

Chronic neuropathic pain or painful neuroma is also possible after vasectomy due to injury of spermatic cord nervous structures. This type of post-surgical pain has primarily been described with nerve damage after other pelvic or inguinal surgery (Ducic et al, 2006). Traumatic neuralgia and neuroma can cause post-vasectomy pain but represent a completely separate entity and require different treatment as was noted in a six case series of this presentation of testicular pain after inguinal herniorrhaphy (Amid, 2006). Patients with traumatic neuralgia typically present earlier than classic PVPS patients (Christiansen and Sandlow, 2003). The neuropathic pain related to injury of a pelvic nerve can cause testicular pain (Ducic I, Dellon AL, 2000) but the presentation, etiology, and treatment options differ for these patients. For this paper, traumatic neuropathic pain or pain due to a neuroma of the genitofemoral nerve is not considered PVPS as it does not usually cause the full syndrome of PVPS.

Incidence of PVPS:

Estimates of the incidence of PVPS vary widely due to the lack of consistent nomenclature and overlap with similar urologic syndromes such as chronic scrotal pain (CSP), chronic pelvic pain syndrome (CPPS), and chronic testicular pain (CTP) that are sometimes used interchangeably. The variability of presenting symptoms, poor long-term surveillance and symptom monitoring after vasectomy, reliance on retrospective questionnaire based studies with typically poor response rates, and patient reticence to seek treatment may contribute to the difficulty in determining the true incidence. Poor compliance with post-vasectomy follow up (for necessary semen analysis) is well documented despite extensive patient education attempts. (Nordlund, et al 1991) Up to a third of patients never return to have even a single semen analysis after vasectomy. (Maatman, et al 1997) This may be partially explained by embarrassment over collection methods. It is possible that some patients with persistent pain do not seek treatment due to similar anxiety or fear. The post-vasectomy instructions given for follow up regarding pain symptoms usually focus on pain arising in the acute post-operative period. The mean time to presentation for post vasectomy pain syndrome is usually months and averages two years or more (Nangia et al, 2000, Selikowitz and Schned, 1985) and this could contribute to missed diagnoses. Education of vasectomy practitioners, a practical definition of PVPS, and surveillance protocols could increase case finding. Pre-vasectomy patient education about PVPS could enhance treatment seeking. Encouraging follow-up for any persistent pain complaints could lead to more timely diagnosis and definitive treatment after presentation.

In one retrospective postal study of chronic post-vasectomy testicular pain (CPTP) that included a non-vasectomized control group (198 patients sent surveys, fifty-one percent response rate), six percent of vasectomized patients had testicular pain severe enough to seek medical assistance, compared to two percent of the control group (Morris et al, 2002). In another questionnaire based retrospective study (460 patients sent surveys, forty-four percent response rate) of chronic scrotal pain (CSP) at one and ten years post-vasectomy, the incidence of pain was 16.8% and 13.8% respectively (Manikandan R, et al, 2004). In another postal questionnaire study with follow up telephone surveys (470 patients sent surveys, 42% response rate) the reported incidence of chronic scrotal pain was 18.7% and it affected quality of life in 2.2% of respondents. The authors concluded that chronic scrotal pain was the most common post-vasectomy complication that may adversely affect quality of life in men undergoing vasectomy. (Choe JM, Kirkemo AK, 1996) In another retrospective postal questionnaire and telephone interview study (McMahon et al, 1992) of 172 men averaging four years after vasectomy, fifty-six patients (33%) reported chronic testicular pain, however, only 30 (17%) found it “troublesome.” In this study they were able to contact 68% of the post-vasectomy patients sent surveys. Testicular pain related to intercourse, as is seen with PVPS, occurred in 5% of respondents in the McMahon study. In a large retrospective postal study of CPTP with a substantially better response rate (560 surveys sent, 71% response rate), they reported an incidence of any testicular pain of 27.2%, but when using pain duration of three months or greater, the incidence was 19% (Ahmed et al, 1997). The only prospective study available surveyed men preoperatively, and again six months later. (Leslie et al, 2007) In this study, 488/593 (82.2%) completed both surveys and 65 (14.7%) reported new onset scrotal pain with an average visual analog score of 3.4/10. Four men (0.9%) reported pain “quite severe and noticeably affecting their quality of life.” Given the mean time to PVPS onset of two years (Nangia, et al 2000), an obvious limitation as to actual incidence was this study’s duration of only six months. In a large series by Moss, congestive epididymitis was noted in six percent after a closed vasectomy and two percent after an open vasectomy, where open versus closed refers to whether the testicular end of the vas was left open or closed. In this large series of 6220 cases, Moss used only ten percent of patients in the series to estimate incidence of “congestive epididymitis” and these cases were all described as “self-limiting, lasting three to seven days,” and were all successfully treated with conservative treatment alone (Moss, WM, 1992). No mention was made of the length of follow-up in the Moss study.

The available studies begin to suggest an incidence of any persistent post-vasectomy scrotal or testicular pain of approximately thirteen to thirty-three percent. Many of these survey studies have low response rates and there is a possibility that men with symptoms are over represented in responses. For some of these men, the pain may not be chronic or meet the time criteria of three months duration. In the study with different groups of patients one and ten years post-vasectomy, the incidence did not change with time suggesting that for some, it is chronic. (Manikandan R, et al, 2004) A smaller unfortunate group of patients report having more severe pain that affects quality of life or sexual function (one to five percent in the studies above). In the McMahon study they found 5% of patients with pain related to intercourse, which is common with PVPS. In the Morris study, six percent of patients sought further medical treatment for their post-vasectomy pain. When using a more rigorous definition as proposed, the incidence would likely be in this lower range. Despite the number of studies to date, the actual incidence of PVPS is hard to state reliably and can only be estimated from these studies. Well-designed prospective studies with duration substantially greater than two years would be required to gain a better estimate of true incidence due to the interval from vasectomy to significant symptoms, and a study of this length may not be practical.

Etiology of PVPS:

The etiology of PVPS has yet to be fully elucidated. Because there is no formal definition and the presentation is variable there have been many hypotheses to explain the syndrome. The currently available evidence suggests several processes that lead to the histological findings seen in pathologic specimens removed to treat severe or persistent PVPS. There may be a final common pathway leading to chronic testicular or epididymal pain that involves damage to scrotal nervous structures via immune system inflammatory effects, back pressure affects in the post-vasectomy closed system, or via perineural fibrosis from either of these processes. Postulated etiologies for PVPS have included pressure from epididymal congestion, inflammation, or compression of paravasal nerves by sperm granuloma (Christiansen and Sandlow, 2003), interstitial fibrosis in the epididymides, or perineural fibrosis (Chen and Ball, 1991).

In one study of the vasectomy sites at vasovasostomy for treatment of PVPS that included a control group of patients with no pain, the histological findings were not helpful in identifying a cause for the pain or predicting which patients would become pain free after the procedure (Nangia et al, 2000). In the Nangia et al study, the mean time to pain onset was two years, but varied widely from nine days to nine years. The mean time interval from vasectomy to vasovasostomy was 4.8 years indicating pain for an average of 2.8 years. The patients were treated with vasovasostomy after a variety of failed conservative treatments that had included NSAIDS, narcotic pain medications, antibiotics, oral steroids, biofeedback and psychiatric evaluation. Five of the thirteen patients had also had regional nerve blocks or lumbar sympathectomy. Of the thirteen patients in the series, four had palpable vasal nodules, of which two were painful and three were found to be sperm granulomas. All four of these patients had vasitis nodosum, chronic inflammation, or significant fibrosis. In four other patients with a tender vasectomy site they found chronic inflammation, or sperm granuloma, fibrosis, suture granuloma, or vasitis nodosa. In the pain-free control group, there were similar findings of vasitis nodosum, inflammation, and nerve proliferation. It was noted that three patients (23%) needed a second surgical intervention (repeat vasovasostomy or epididymectomy) to become pain free. The authors suggested that this implied an obstructive etiology in these cases. Including these three, nine of thirteen became pain free in the series. In the remaining four patients, one had unilateral reoccurrence and was managed with NSAID therapy. Another was pain free for a year and had bilateral reoccurrence and semen analysis confirmed re-obstruction (Nangia et al, 2000).

Studies of epididymectomy specimens from patients with post-vasectomy pain have shown evidence of pathological changes possibly related to longstanding obstruction. This interstitial fibrosis and perineural fibrosis seen in the epididymides of affected men could explain the pain. (Chen and Ball, 1991) Nariculam et al also reported this finding of obstructive changes in all of the epididymectomy specimens in their study of chronic testicular pain. They noted epididymal fibrosis, tubule distension, and focal fibrosis as well as signs of testicular tubular sclerosis and inflammation (Nariculam et al, 2007). Some of the specimens in the Nariculam study showed evidence of testicular infarction suggesting intermittent torsion and the study was not PVPS specific.

Animal studies of the effects of vasectomy on the epididymis may not be directly applicable, but several summary statements can be made that are likely not species specific: “The epididymal interstitium shows microscopic changes indicative of chronic inflammation, with infiltration of macrophages, lymphocytes, and plasma cells, and rats with these lesions have higher antisperm antibody levels than animals lacking epididymal changes. Macrophages and neutrophils may enter the duct through the epididymal epithelium, at sites of rupture of the duct, and in the efferent ductules. Cyst-like spermatic granulomas occur in virtually all species where the epididymis or vas deferens ruptures with escape of spermatozoa. The sites and timing of granuloma formation may depend on the mechanical properties of the tract in different species, and they are probably important in the immune response to vasectomy” (Flickinger et al, 1995).

Testicular damage has been described in most mammalian studies that have specifically looked at histological changes after vasectomy. There are several human studies in the literature that have reported similar post-vasectomy testicular damage that worsens with obstructive interval. These findings have included degeneration of spermatids, reduced spermatogenesis, testicular interstitial fibrosis, loss of Sertoli cells, decreases in depth of the epithelium and increases in thickness of the basement membrane or peritubular fibrosis (Jarow et al, 1985, Jarow et al, 1994, Raleigh et al, 2004, McVicar et al, 2005, White et al, 2000). In some studies of post-vasectomy testicular pathology there was also a general finding of decreased fertility after vasovasostomy in the specimens with significant scarring or focal interstitial fibrosis (Jarow et al, 1985, McVicar et al 2005). It has been postulated that these changes are due to the increased pressure proximal to the testicular end of the vas, or are inflammatory or autoimmune in nature.

One of the factors affecting acceptance of an explanation for pain in PVPS patients is the lack of symptoms in the majority of vasectomized men. Any explanation for the pain should include a description of a pathologic process that could be present in the minority of men that develop PVPS. The autoimmunity that develops to sperm after vasectomy may be an area that deserves scrutiny in this regard. Vasectomy affects structures proximal to the testicular end of the vas and damages the blood-testes and blood-epididymus barriers either via inflammation or pressure related changes. The compromise of these physiologic barriers and “epididymal blowouts” cause extravasation of sperm and the formation of a variety of antibodies, some of which have been studied. Most of the studies on these antibodies have focused on the effect of anti-sperm surface antibodies on fertility, and no studies exist on the effects of these antibodies in the epididymides in PVPS patients. The Jarow study from 1994 found no correlation between anti-sperm antibody status and testicular fibrosis, but used the immunobead anti-sperm antibody detection method, which only detects sperm surface antibodies. The possibility of anti-sperm antibodies to internal sperm antigens, sperm enzymes, or sperm proteins that are assembled in the testes (resulting from antibody formation to breakdown products of sperm in the epididymides or in sperm granulomas) has not been studied. If antibodies are created to sperm enzymes or testicular proteins, the resulting inflammation could cause epididymal or testicular fibrosis and pain. In the study by Batova et al, they found that vasectomized men had antibodies to testicular NASP and suggested that the autoantibodies in vasectomy sera behave as anti-peptide antibodies (Batova et al, 2000). The possibility that antibodies form against sperm components has been proven to occur to sperm protamines (Samuel at al 1978) as well as to other sperm proteins including sperm-specific DNA-polymerase (Samuel et al, 1975) and testicular nuclear autoantigenic sperm protein (tNASP) (Batova et al, 2000). Previous work showed that 86% of vasectomized patients with anti-sperm antibodies had anti-tNASP antibodies (Richardson et al, 1993). These antibodies have not been fully characterized and their effects may play a role in the inflammatory damage seen in specimens obtained at epididymectomy or orchiectomy in PVPS patients.

The animal and human literature on the post-vasectomy formation, types, and effects of anti-sperm antibodies is extensive and beyond the scope of this paper. The available animal studies lead to the conclusion that the autoimmune response to vasectomy is species specific and perhaps even strain specific in its effects. (Alexander and Anderson, 1979) The article by Alexander and Anderson is one of the most extensive papers on this subject and more contemporary studies have added little to help explain any specific link between these antibodies and the development of PVPS. Even if a link were found, the antibodies are persistent and there is no way to remove them. The damage to the blood/testes barrier and epithelial tight junctions in the epididymides may not be reparable with vasovasostomy and some animal studies have shown an increase in anti-sperm antibody titers after vasovasostomy (Flickinger et al, 1995, Herr at al 1985).