Long-Term Risks of Vasectomy
Amy E. Pollack and Mark A. Barone
Table Of Contents
Amy E. Pollack, MD, MPH
Mark A. Barone, DVM, MS
EFFECTS ON SEXUALITY AND SEXUAL FUNCTION
CHANGES IN TESTES
EFFECTS ON THE EPIDIDYMIS
EFFECTS ON PROSTATIC FUNCTION
HUMAN IMMUNODEFICIENCY VIRUS AND VASECTOMY
COMPREHENSIVE STUDIES OF DISEASE INCIDENCE
COMPREHENSIVE STUDIES OF DISEASE PREVALENCE
EFFECTS ON CARDIOVASCULAR SYSTEM
VARIOUS PHYSIOLOGIC EFFECTS
POSTVASECTOMY PAIN SYNDROME
OVERALL MORTALITY RATES
Because vasectomies are usually performed on men who are in their thirties and forties at the time of the procedure, several decades of life remain after vasectomy during which long-term effects on health might manifest themselves. Because large numbers of men are exposed to such a risk for a long period of time, an adverse effect of vasectomy on health would have far-reaching negative consequences for public as well as individual health.
Concern about the possibility of long-term risks of vasectomy was fueled by findings that vasectomy may accelerate development of atherosclerosis in monkeys,1,2 but it originated in observations that a high proportion of men with vasectomy develop anti-sperm antibodies.3,4,5,6,7,8,9 Results of studies conducted over the past few decades provide little evidence of any significant long-term side effects of vasectomy. Nonetheless, the topic remains of considerable interest.
|EFFECTS ON SEXUALITY AND SEXUAL FUNCTION|
After vasectomy, male sexual and reproductive physiology remains unaffected, aside from the desired change in fertility. The nerves involved in erectile function and ejaculation are not affected, and vasectomy does not lead to impotence or other sexual difficulties. In a large cohort study,10,11 incidence of impotence was 1.9/1000 man-years (MY) of observation in men with vasectomy and 1.7/1000 MY in men without vasectomy, a difference that was not statistically significant.
As with female sterilization, vasectomy has sometimes been reported to have a positive effect on sexuality, possibly because the chance of unintended pregnancy has been reduced.12,13,14 In one large study, the number of men reporting loss of sexual interest was identical in vasectomized versus nonvasectomized men.15
Production of seminal fluid, the major component of semen, by the accessory sex glands is unaffected by vasectomy. Thus, the client will not notice any reduction in the amount of semen ejaculated after vasectomy has been performed. Sperm production continues, even though the sperm's passage through the reproductive tract has been blocked, and sperm are broken down by macrophages in the lumen of the epididymal tubule.3,16 Sometimes the blockage in the reproductive tract after vasectomy causes pressure to build up in the epididymis, which causes the tubules to distend and, in time, rupture. Ruptures are usually asymptomatic and not problematic. Sperm granulomas that can form at the site of the rupture do not usually require treatment. Although some vasectomists believe that this buildup can be avoided by leaving open the testicular end of the vas, the effect of this “open-ended” technique on failure rates has not been adequately studied.
Although some early prospective endocrine studies suggested that mean plasma levels of testosterone, luteinizing hormone (LH), and estradiol increased after vasectomy when compared with mean hormone levels measured before vasectomy, the changes were found to be inside the normal range for adults.17 Studies in animals suggesting an effect of vasectomy on testicular weight and Leydig cell morphology, which were never confirmed,18,19,20 generated sufficient concern that a large number of studies regarding endocrine function in man have been done. The results of these studies are summarized in Table 1.
In nearly all longitudinal studies and all of the cross-sectional studies (with the exception of that of Mo and colleagues, who reported significantly higher testosterone levels in men >20 years postvasectomy compared with age-matched controls), no significant association of vasectomy with changes in the concentrations of testosterone, LH, or follicle-stimulating hormone (FSH) was found. Thus, despite isolated findings of a significant association of vasectomy with changes in some hormones, the bulk of the extensive research on the subject provides strong evidence that vasectomy has no effect on testosterone or the pituitary gonadotropins at least up to 25 years after the operation.
|CHANGES IN TESTES|
Although the testes maintain some of the normal ultrastructure following vasectomy,44 several studies have demonstrated that some histologic changes occur in the testes following vasectomy.20,45,46,47,48,49,50,51
Electron microscopic examination of sections of the seminiferous tubules from the testes of vasectomized men showed that some of the normal ultrastructure was maintained:
The blood supply to the tubules was intact.
Histologic abnormalities noted, however, include sperm abutting the basal portion of the Sertoli cells, instead of being observed in their typical location close to the lumen,44 increased thickness of the seminiferous tubular walls,20,49,51 reduced mean number of Sertoli cells and spermatids per tubular cross-section,49 and increased focal interstitial fibrosis.20,49,51
How these changes occur and their significance remain unclear. Some men with these changes have been able to produce offspring following vasectomy reversal.47,49,50 In the one study in which fertility was examined in relation to histologic changes, interstitial fibrosis was significantly correlated with infertility in patients who had a successful vasectomy reversal determined by sperm in the ejaculate. None of the other vasectomy-associated histologic abnormalities were associated with infertility after vasectomy reversal.49
|EFFECTS ON THE EPIDIDYMIS|
Although numerous studies have examined the effects of vasectomy on the epididymis in various laboratory animals, similar studies in men are lacking.52 Epididymitis, because of continued passage of sperm from the testis into the epididymis following vasectomy, is uncommon, being reported in up to 6% of men who have had a vasectomy.53 This condition has been referred to as “congestive” epididymitis and is only rarely due to infection.
Some degree of epididymal dilatation or distension has been reported in 70% to 100% of the men undergoing vasectomy reversal, but most men do not have any symptoms.54,55,56 Ultrasound studies have found that epididymal enlargement is common and may not be associated with any pain or discomfort.57,58 The mechanism whereby sperm can be accommodated in the human epididymis is still not known, but at least clinicopathologically, it does not resemble the events that occur in the rabbit, rat, and hamster, where despite species' variation in the ability of the proximal vas and epididymis to distend following vasectomy, the epididymis may ultimately rupture.52
|EFFECTS ON PROSTATIC FUNCTION|
Thakur and colleagues studied maltase activity in semen, which reflects the secretory activity of the prostate, in 35 men vasectomized for 1 to 2 years and a comparison group of 24 nonvasectomized men.59 They found that maltase activity in the semen of vasectomized men was significantly lower than in nonvasectomized men and concluded that prostatic function was diminished by vasectomy. These findings were confirmed by Naik and associates who demonstrated that, in 78 men vasectomized for 1 to 8 years, seminal concentrations of maltase, in addition to prolactin, zinc, and magnesium, were significantly lower than in 22 nonvasectomized men of normal fertility.60
However, total prostatic volume and growth rate do not appear to be affected by vasectomy.61 More recently, Lassen and colleagues62 demonstrated that postvasectomy prostate-specific antigen levels were significantly lower than preoperative levels for up to 6 months after vasectomy.
Implications of these findings on changes in the secretory function of the prostate after vasectomy remain unknown. Further epidemiologic research on noncancerous prostatic disease in vasectomized men, in particular the relationship of the changes noted already to benign prostatic hypertrophy would be of interest.
|HUMAN IMMUNODEFICIENCY VIRUS AND VASECTOMY|
Human immunodeficiency virus (HIV) can be found in seminal white blood cells (WBC), and these cells may play a role in the sexual transmission of HIV.63,64 Because semen from vasectomized men contains significantly fewer WBCs than nonvasectomized men,65,66 some have questioned whether vasectomy may be used to decrease sexual transmission of HIV.67,68
Preliminary data from Anderson and coworkers indicated that infectious HIV could be found in semen from some HIV seropositive vasectomized men.66 More recently, 46 HIV-seropositive men were studied before vasectomy and for 3 months afterward; although levels of cell-free virus in the semen remained stable after vasectomy, cell-associated HIV was detected in significantly more men after vasectomy.69 Taken together, these results provide good evidence that vasectomy provides no protection against HIV transmission. This underscores the importance of counseling vasectomized men that vasectomy does not provide any protection against transmission or acquisition of HIV and other sexually transmitted diseases (STDs) and that men need to use condoms consistently and correctly if they are at risk of transmitting or acquiring HIV/STDs.
|COMPREHENSIVE STUDIES OF DISEASE INCIDENCE|
Four large-scale, retrospective cohort studies have examined comprehensively the incidence of a number of diseases in vasectomized men and a comparison group of nonvasectomized men.70,71,72,73,74 In each, investigators identified retrospectively by computer a group of men who were known to have vasectomies and a comparison group of men not known to have had a vasectomy. The occurrence of hospitalizations after identification for the study was determined by computer-record linkage. The comparison groups were men hospitalized in the same years for an operation other than vasectomy;70,71 men with the same prepaid medical care program;72 men having routine health checkups who did not indicate on questionnaires that they had had a vasectomy previously;73 and men admitted to the hospital for elective operations, appendicitis, or injury.74 The designs of these four studies are summarized in Table 2, and the results of their comparison of disease incidence in vasectomized and nonvasectomized men are summarized in Tables 3 and Table 4.
Of greatest importance, in all four studies, vasectomy was not significantly associated with increased risk of hospitalization for most disease categories. The total number of cases of disease in men in these studies is large for all categories and taken together, the studies are reassuring that vasectomy does not increase the risk of adverse health outcomes.
In the study by Walker and associates,72 vasectomy was associated with a significantly higher risk of diseases of the genitourinary system, including orchitis and epididymitis. The increase in risk was confined to the first years after vasectomy, and the authors attributed the findings to the occurrence of minor complications of vasectomy and to the possibility that men who had recently undergone vasectomy might be more likely to seek medical attention for nonvasectomy-related genitourinary conditions.
In three of the studies,70,71,72,73 the risk of hospitalization for mental disorders was lower in vasectomized men than in the comparison group. The most likely explanation is that men who elect to have a vasectomy are mentally more stable, because a causal relationship of vasectomy to better mental health is unlikely.
Walker72 and Petitti 73 and respective coworkers studied the risk of hospitalization separately in men with vasectomies of long duration—9 or more years in the Walker study and 10 or more years in the Petitti study. In both, there was no significant association of vasectomy of long duration with an increased risk of hospitalization for any of the categories of disease shown in Table 3.
Massey and colleagues reported the results of the fifth large retrospective cohort study, which examined the incidence of 98 diseases or conditions in 10,590 paired vasectomized men and neighborhood controls matched for age, race, and marital status.10 Additional data on this cohort were later reported by Schuman and associates.11 Of particular interest to those authors were diseases or conditions that could have been the immunopathologic consequences of anti-sperm antibodies. The median time of follow-up postvasectomy was over 8 years, ranging from 1 to 41 years. With the exception of epidid-ymitis/orchitis, the occurrence of all other diseases examined was similar or lower in vasectomized men compared with controls. This included diseases or conditions in which a vasectomy-related immunopathologic mechanism may have played a role. The number of cases of epididymitis/orchitis was relatively low (33 per 10,000 MY in vasectomized men), and the major difference in occurrence between the vasectomized men and controls was during the first 12 months after vasectomy.
|COMPREHENSIVE STUDIES OF DISEASE PREVALENCE|
Petitti and colleagues15 also did a cross-sectional analysis in which they examined the prevalence of a large number of diseases and the existence of current symptoms of illness in 4,385 vasectomized and 13,155 nonvasectomized men enrolled in the Kaiser-Permanente Medical Care Plan. Of 45 diseases and symptoms that were examined, vasectomy was significantly, independently associated with joint pain or swelling, back trouble, and a history of kidney or bladder infection. The latter finding is consistent with the findings of Walker and associates72: that is, a higher risk of diseases of the genitourinary system in vasectomized men, although details on whether risk of kidney or bladder infection was elevated are not provided by Walker's group. No other studies have examined specifically the possibility of an association of vasectomy with joint pain or swelling and back trouble, although the occurrence of arthritis15 or the risk of hospitalization for arthritis10,11,72,74 have not been shown to be higher in vasectomized than in nonvasectomized men.
|EFFECTS ON CARDIOVASCULAR SYSTEM|
Intense research efforts examining the association between vasectomy and cardiovascular disease in men were touched off by studies reporting that vasectomized monkeys had atherosclerosis of greater extent and severity than nonvasectomized monkeys.1,75 It was postulated that vasectomy could increase the risk of atherosclerosis if anti-sperm antibodies that form as a consequence of vasectomy resulted in the production of circulating immune complexes that injure the vascular wall. Concern about the possibility that vasectomy might increase the risk of atherosclerotic cardiovascular disease in men has waned since publication of a large number of studies showing no association of vasectomy with various disease endpoints in men. In addition, two experimental studies, which attempted to replicate the original studies that showed an effect of vasectomy on atherosclerosis in monkeys, included larger numbers of monkeys and found no adverse effect of vasectomy on atherosclerosis.76,77
Since the early 1980s, numerous cohort, case-control, and cross-sectional studies have been conducted to examine potential associations between vasectomy and various cardiovascular disease endpoints, including acute myocardial infarction, other ischemic heart disease, stroke, nonsyphilitic aortic aneurysm, peripheral vascular disease, hypertension, coronary artery disease, and hypertensive and atherosclerotic retinal vascular changes. Table 5 provides a summary of studies on vasectomy and cardiovascular disease. These epidemiologic studies of cardiovascular disease in vasectomized men have, with few exceptions, shown no association of vasectomy with any manifestation of atherosclerosis or cardiovascular disease. Even in men with vasectomies of long duration (20 years or longer), no association of vasectomy with an increased risk of cardiovascular disease has been found.73,78,79,80 Taken together, the newer experimental studies in monkeys76,77 and accumulated epidemiologic studies in men provide strong reassurance that vasectomy has no adverse effect on the cardiovascular system nor does it increase the risk of atherosclerosis in man.
|VARIOUS PHYSIOLOGIC EFFECTS|
In the late 1960s and the early 1970s, Roberts91,92 suggested that the risk of thrombophlebitis might be increased following vasectomy. Results of a large-scale epidemiologic study, however, did not find increased risk of thrombophlebitis in vasectomized men.10,11 In a prospective study, various measures of blood coagulation function were examined in 38 men before vasectomy and for 12 months following vasectomy and at the same timepoints in an age-matched, nonvasectomized comparison group.93 No differences were found between the vasectomized and the nonvasectomized men in any measures examined including prothrombin time, partial thromboplastin time, spontaneous platelet aggregation, circulating platelet aggregation ratios, or levels of fibrinogen, Factor V, Factor VII, fibrin monomer, and fibrin digestion products.
Petitti and coworkers94 used information from comprehensive multiphasic health checkups in 4,385 vasectomized and 13,155 age- and race-matched, nonvasectomized men to study the association of vasectomy with a large number of physiologic measures. In this group, vasectomy was not significantly associated with alterations in any of the following: diastolic blood pressure, white blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, mean cell volume, mean corpuscular hemoglobin concentration, sodium, calcium, cholesterol, glucose, uric acid, blood urea nitrogen, creatine, total bilirubin, alkaline phosphatase, lactic dehydrogenase, and glutamic-oxaloacetic transaminase. The vasectomized men had a significantly higher mean serum potassium concentration (4.6 versus 4.5 mEq/L) and significantly lower systolic blood pressure (128.9 versus 130.4 mm Hg) than nonvasectomized men. The overall differences in these measures, although statistically significant, were considered unlikely to be biologically important even if they were causally associated with vasectomy. In three additional studies that examined the effect of vasectomy on systolic and diastolic blood pressure, two found that the mean systolic and diastolic blood pressures were not significantly different between vasectomized and nonvasectomized men;83,95 the other found that both were lower in vasectomized men than in nonvasectomized men.96 Verheught and associates measured serum cholesterol before and 3 months after vasectomy in 24 men and in a control group of 23 men of similar age.97 No significant differences in cholesterol concentration were measurable between the two groups at baseline, nor was a significant change in cholesterol found after vasectomy.
Taken together, these studies indicate that vasectomy is not associated with changes in the physiologic functions measured by these tests.
An increased occurrence of circulating sperm-agglutinating antibodies in vasectomized men was first reported by Phadke and Padukone in 1964.3 Subsequently, numerous investigators have confirmed the presence of anti-sperm antibodies in association with vasectomy.4,5,6,7,8,9,98,99,100
The clinical significance of anti-sperm antibodies in men after vasectomy has been the subject of many investigations, and a number of potential mechanisms whereby they might lead to disease have been suggested including anti-sperm antibodies might trigger production of antibodies to other cells which might lead to disease; sperm antigens may combine with the anti-sperm antibodies to produce circulating immune complexes that could cause tissue damage and inflammation;1 and vasectomized men may have immunity to tumor-associated antigen that could affect directly the development of tumors.101
However, numerous studies conducted over the past few decades have shown no evidence of any immunologic or other diseases related to development of anti-sperm antibodies following vasectomy.5,10,72,80,82,102,103 Anti-sperm antibodies have been associated with decreased fertility following vasectomy reversal (see Chapter 48, Reversing Vasectomy).
Because sperm first form at puberty, they are autoantigenic. Normally, sperm antigens are not exposed to the immune system because of the blood-testis barrier and other epithelial barriers along the reproductive tract. Development of anti-sperm antibodies after vasectomy is thought to be related to breakdown of the blood-testis barrier104 and leakage of sperm antigens from the epididymis.96 Sperm antigens have been found in the serum of men as early as 2 weeks after vasectomy.105
Antisperm antibodies are found in between 8% and 21% of men in the general population and in 9% and 36% of infertility patients.104 In contrast, circulating sperm agglutinating antibodies are found in 50% to 80% of men in the first year after following vasectomy.3,4,5,6,7,8,9,106 Approximately 3% of nonvasectomized men have sperm-immobilizing antibodies96 whereas anywhere from 25% to 60% of men develop sperm-immobilizing antibodies in the first year after vasectomy.6,7,8,9 A small percentage of men who do not develop anti-sperm antibodies in the first year after vasectomy develops them in the second or third year after the procedure.5,107
Although serum anti-sperm antibodies are common following vasectomy, fewer men have these antibodies in their seminal plasma.108 Following surgery for vasectomy reversal, however, anti-sperm antibodies are more commonly found in seminal plasma104 and are found on the surface of sperm as well.104,109
Antibodies to protamines, proteins found in the nucleus of the sperm, are detectable in between 20% and 40% of vasectomized men but are virtually undetectable in nonvasectomized men.98,99,100,110 The presence of antiprotamine antibodies has been of special concern because of fear that vasectomy might lead to formation of anti-deoxyribonucleic acid (DNA) antibodies, because DNA is the other main constituent of the sperm nucleus. To date, however, anti-DNA antibodies have not been detected in vasectomized men.98,100
Large variations occur in the titers of both sperm-agglutinating and sperm-immobilizing antibodies in men following vasectomy.8,96 Few studies have examined what happens to anti-sperm antibody titers over time. The results of those that have examined the issue are conflicting, with some investigators111,112 reporting no change and others7,96 reporting an increase over time.
Little is known about the factors that affect either the development of anti-sperm antibodies or the titer of the antibodies in the men who do develop them. Some evidence suggests that age at vasectomy plays a role, with younger men being more likely than those older to develop anti-sperm antibodies.96,100 A family history of autoimmune disease is not associated with development of anti-sperm antibodies.100
If development of anti-sperm antibodies caused or was accompanied by the development of other antibodies, particularly other autoantibodies, a mechanism linking vasectomy with disease in men would be established, because many diseases in humans are associated with increases in autoantibody levels.
Several investigators have studied this possibility by examining the presence of various autoantibodies including rheumatoid factor and anti-thyroid, anti-nuclear, anti-mitochondrial, anti-parietal cell, anti-thyroid, anti-thyroglobulin, anti-liver, antikidney, and anti-smooth-muscle antibodies in men before and after vasectomy or in vasectomized compared with findings in nonvasectomized men.9,99,100,113,114,115,116,117,118 Results of these studies indicate that vasectomy is not associated with clinically significantly increased levels of autoantibodies other than anti-sperm antibodies.
Although two studies reported that vasectomized men developed cytotoxic antibodies,119,120 results of larger, well-designed studies using before-and-after measures of cytotoxic antibodies were unable to demonstrate any change in the level of cytotoxic antibodies after vasectomy.9,121,122
Finally, results of several large-scale epidemiologic studies have not shown an increased incidence or prevalence of autoimmune disease in vasectomized compared with findings in nonvasectomized men. 10,11,70,71,72,73,74
Thus, taken together, these studies provide convincing evidence that vasectomy does not lead to development of autoantibodies in man other than anti-sperm antibodies.
Circulating Immune Complexes
Immune complexes form when an antibody combines with its antigen, and in some circumstances, immune complexes may be deposited in tissues such as the renal glomerulus, joints, and arterial walls, leading to inflammation and tissue necrosis. It has been suggested that continuous production of anti-sperm antibodies after vasectomy could lead to the formation of circulating immune complexes with subsequent development of various diseases. Some investigators have hypothesized or demonstrated this is to be the case in laboratory animals following vasectomy, including atherosclerosis in monkeys1 and orchitis and glomerulonephritis in rabbits.123
Studies to detect circulating immune complexes in vasectomized men have produced conflicting results. Several investigators have demonstrated the presence of circulating immune complexes in small percentages of men following vasectomy.113,124,125 One study demonstrated a higher incidence and higher levels of circulating immune complexes in men who were vasectomized for a mean of nearly 8 years compared with those in age-matched controls.126 Numerous others, however, have reported no association of vasectomy with circulating immune complexes or have demonstrated only a transient increase in circulating immune complexes following vasectomy, which disappear by 3 months to 1 year after vasectomy.86,99,100,105,118 In the study with the longest follow-up after vasectomy, no differences were found in the level of circulating immune complexes in vasectomized men (mean time since vasectomy nearly 16 years) compared with those in nonvasectomized men.96
Although the evidence indicates that at least in some men and for some time, circulating immune complexes occur following vasectomy, they do not appear to be clinically relevant. Results of a number of large-scale epidemiologic studies have not shown increased incidence or prevalence of various diseases that could be related to immune complex deposition, including atherosclerosis and glomerulonephritis in vasectomized compared with nonvasectomized men.10,11,71,73,74,87
Incidence of prostate cancer is rising, and in the United States it is the most commonly diagnosed cancer among men.127,128 Although this may be due at least in part to enhanced screening and detection, these are unlikely to be the only factors involved.127 Little is known about the etiology and pathogenesis of prostate cancer, and few risk factors have been identified. Family history of prostate cancer appears to be an important risk129,130 and incidence increases with age, varies with ethnicity, and shows wide geographic variation.131 Black Americans have the highest incidence of prostate cancer in the world, nearly twice that of white Americans. Asians have a low incidence of prostate cancer. Geographic variation is not solely explained by ethnicity; for example: American blacks have twice the incidence of prostate cancer that Zimbabwean blacks have,132 American whites have twice the incidence of prostate cancer that European whites have,131 and incidence of prostate cancer among Japanese immigrants in the United States is higher than among Japanese in Japan.133 Dietary fat intake may be an important risk factor.134,135,136
Over a dozen epidemiologic studies of vasectomy and the risk of prostate cancer have been reported in the literature since the mid-1980s (Table 6). Results of these studies have been difficult to interpret for several reasons: research findings have been found in conflict; a convincing biologic mechanism for a causal relationship has been lacking; when associations have been found, they have been generally weak; and some studies have had the potential for bias (detection, misclassification, recall and/or confounding bias).
In 1990, there was a report of a case-control study showing a threefold to sixfold increased risk of prostate cancer in vasectomized men.140 The methodology used in this study was to screen data gathered from hospital interviews to look for associations between risk factors and diseases. Associations identified in studies using this methodology often appear more highly significant than they actually are.152 In a subsequent report of another case-control study by the same authors using additional data from the same surveillance system, a lower and nonsignificant association between vasectomy and prostate cancer was described.146
There were four other case-control studies and one cohort study published in the late 1980s and early 1990s. Two of the five studies reported a moderate but significant elevated risk of prostate cancer in vasectomized men,139,142 one reported a nonsignificantly increased risk,138 and the other two reported no increased risk.137,153 Limitations, including detection and misclassification bias, were possible in all of these studies.154
Two cohort studies published in 1993 by Giovannucci and coworkers reported weak positive associations between vasectomy and prostate cancer and relative risks that increased over time.143,144 These studies provided the best evidence for a causal link between vasectomy and prostate cancer and prompted the U.S. National Institutes of Health (NIH) to convene a panel of experts to review the data available at that time. The panel concluded that the associations that had been reported to date were weak and that there was a strong potential for detection bias in the studies because much prostate cancer is undetected and underreported, and because vasectomized men may be more likely than other men to be screened for prostate cancer or seek health care services, leading to the appearance of an elevated risk of prostate cancer in vasectomized men.155
Since that time, there have been eight additional studies on vasectomy and prostate cancer published.11,145,146,147,148,149,150,151 Seven showed no increased relative risk of prostate cancer in vasectomized men, although one study reported a nonsignificant increased risk in vasectomized black men in the United States.146 In the one study that demonstrated a significant elevation of risk of prostate cancer in vasectomized men, the patients also had very high rates of prostatitis and benign prostatic hypertrophy compared with controls, indicating a high likelihood of detection bias.148 These more recent studies confirm the probability that some of the earlier studies were subject to bias.
Epidemiologic studies of relatively weak associations between a procedure such as vasectomy and a chronic disease such as prostate cancer are difficult because of the potential for bias.128 Authors of a recent metaanalysis of published studies on vasectomy and prostate cancer concluded that numerous sources of bias have likely led to an overestimation of any effect of vasectomy on prostate cancer.156 Taken as a whole, these studies provide little evidence for a causal association between vasectomy and prostate cancer, especially given that results of studies have been inconsistent, associations when found have been mostly weak and potential for biases large, and there is no plausible biologic mechanism.157 More recent studies support the conclusions of the NIH panel of experts that no change in current practice of vasectomy is warranted, that providers should continue to offer vasectomy, that vasectomy reversal is not warranted to prevent prostate cancer, and that screening for prostate cancer should not be any different in men who have had a vasectomy than in those who have not.155
Table 7 summarizes results of epidemiologic studies of vasectomy and testicular cancer. With one exception,162 the studies conducted between the 1970s and early 1990s that showed an increased risk of testicular cancer following vasectomy were not statistically significant.70,159,160,161 These studies included only small numbers of vasectomized men with testicular cancer and were subject to confounding and/or misclassification bias. Three other studies reported no increased risk,74,146,158 and Giovannucci and coworkers80 found no cases of testicular cancer among nearly 15,000 vasectomized men. Two addi-tional studies included the largest numbers of cases of testicular cancer among vasectomized men and found no increased risk.147,163 Taken together, results of these epidemiologic studies provide convincing evidence that vasectomy is not associated with an increased risk of testicular cancer.
Information on the risk of urolithiasis in vasectomized men is available from five studies (Table 8). No significant increase in risk was reported in three of these five studies.11,15,74 Kronmal and associates,164 examining data from the Coronary Artery Surgery Study registry, first reported a significantly increased risk of urolithiasis in vasectomized men in the late 1980s. More recently, the same investigators found a similar increased risk of urolithiasis in vasectomized men under 46 years of age, but not in those men who were 46 or over at the time of the study.165 The mechanism by which vasectomy might increase the risk of urolithiasis is obscure. The public health impact of an increase in the risk of urolithiasis of the magnitude suggested in the accumulated studies to date is small.
|POSTVASECTOMY PAIN SYNDROME|
Chronic testicular pain has been reported by a small percentage of men after vasectomy and has been called postvasectomy pain syndrome.58,166,167 In one study that included 172 patients surveyed four years after vasectomy,58 56 patients (33%) reported some type of chronic testicular discomfort following vasectomy. Twenty-six (15%) considered this pain to be troublesome, nine (5%) sought medical care, and only three patients (<2%) regretted having had the vasectomy because of chronic pain. Likewise, in another study, 34 of 182 (18.7%) reported some postvasectomy pain 2 to 7 years after vasectomy.166 However, 71% said the discomfort was only occasional and was not troublesome or was only a minor nuisance. Just over 2% reported that the pain had a negative impact on their life. In rare instances, in which conservative therapy such as nonsteroidal anti-inflammatory drugs, sitz baths, antibiotics, or spermatic cord blocks fails, vasectomy reversal or denervation of the spermatic cord may be useful options.168,169 The cause of postvasectomy pain syndrome is poorly understood and may be related to infection, epididymal engorgement with sperm, sperm granuloma formation resulting from back pressure-induced rupture of epididymal tubules, or nerve entrapment.168,170,171 There is, however, no convincing evidence that postvasectomy pain arises from the testes.53
|OVERALL MORTALITY RATES|
Overall mortality rates in vasectomized and nonvasectomized men has been examined in three large cohort studies10,11,80,81, and was found to be lower in vasectomized men in all three studies (Table 9). The most likely explanation for the lower mortality rates in vasectomized men is selection bias: that men who have had a vasectomy represent a self-selected group who may be healthier or seek health care more readily than nonvasectomized men. Authors of two of the studies suggested that the most appropriate interpretation of these data was that no evidence suggested that vasectomy leads to an overall increase in mortality rates.10,80
There have now been over 2 decades of intense research on potential long-term health effects of vasectomy. This research provides reassurance that vasectomy does not have any significant long-term negative effects and does not increase the risk of cardiovascular disease, which is the major cause of morbidity and mortality in men in developed and most developing countries. Vasectomy appears to be a largely safe and highly effective method of fertility control with a risk profile that compares favorably with that of methods of fertility control used by women.
* In men >20 years postvasectomy, testosterone levels were significantly higher than in age-matched controls.
0, no significant change; + , statistically significant increase; NM, not measured
* Where given
† Ratio of standardized first-event rate in vasectomized men to average of standardized first-event rates in the three comparison groups
(Adapted from references 70 to 73)
* Relative risk in men with a vasectomy compared with combined controls.
(Adapted from Nienhuis et al: Incidence of disease after vasectomy: A record linkage retrospective cohort study. BMJ 304;743, 1992)
* All men in study had some degree of coronary artery disease
† Number of pairs in which a case occurred in one or both members
NR = not reported
* Number of years postvasectomy.
NR, not reported.
NR, not reported.
* Total deaths among all men in cohort.
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