This chapter should be cited as follows: This chapter was last updated:
Barone, M, Pollack, A, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10409
August 2008

Sterilization

Long-Term Risks of Vasectomy

Mark A. Barone, DVM, MS
EngenderHealth, New York, New York, USA
Amy E. Pollack, MD, MPH
Columbia University, New York, New York, USA

INTRODUCTION

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, 10 Results of studies conducted over the past three 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,11, 12 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.13, 14, 15 In one large study, the number of men reporting loss of sexual interest was identical in vasectomized versus nonvasectomized men.16

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.4, 17 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.

ENDOCRINE/HORMONAL EFFECTS

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.18 Studies in animals suggesting an effect of vasectomy on testicular weight and Leydig cell morphology, which were never confirmed,19, 20, 21 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,22 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,23 several studies have demonstrated that some histologic changes occur in the testes following vasectomy.21, 24, 25, 26, 27, 28, 29, 30, 31

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.
  The lumen of each tubule examined was patent.
  The Sertoli cells appeared to be intact.
  The germinal epithelium was present and showed normal stages of spermatogenesis.
  The spermatids were seen in the usual clusters of four to five.23

Histologic abnormalities noted, however, included sperm abutting the basal portion of the Sertoli cells, instead of being observed in their typical location close to the lumen,23 increased thickness of the seminiferous tubular walls,21, 28, 30, 31 reduced number of spermatids,28, 31 increased focal interstitial fibrosis,21, 28, 30, 31 and decreased numbers of sperm/gram of testis.31

How these changes occur and their significance remain unclear. Some men with these changes have been able to produce offspring following vasectomy reversal26, 28, 29 or assisted reproduction.31 In 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, but none of the other vasectomy-associated histologic abnormalities were associated with infertility after vasectomy reversal.28

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.32 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.33 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 70–100% of the men undergoing vasectomy reversal, but most men do not have any symptoms.34, 35, 36 Ultrasound studies have found that epididymal enlargement is common and may not be associated with any pain or discomfort.37, 38 On ultrasound examination, vasectomized men had a significantly higher incidence of thickened epididymides, epididymal tubular ectasia (when the normally invisible epididymal tubules are visible) and sperm granulomas compared to non-vasectomized controls, although these changes did not appear clinically significant.39

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.32

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 1–2 years and a comparison group of 24 nonvasectomized men.40 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 1–8 years, seminal concentrations of maltase, in addition to prolactin, zinc, and magnesium, were significantly lower than in 22 nonvasectomized men of normal fertility.41

However, total prostatic volume and growth rate do not appear to be affected by vasectomy.42 More recently, Lassen and colleagues43 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.44,45 Because semen from vasectomized men contains significantly fewer WBCs than nonvasectomized men,46,47 some have questioned whether vasectomy may be used to decrease sexual transmission of HIV.48,49

Preliminary data from Anderson and coworkers indicated that infectious HIV could be found in semen from some HIV seropositive vasectomized men.47 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.50 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.51, 52, 53, 54, 55 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;51, 52 men with the same prepaid medical care program;53 men having routine health checkups who did not indicate on questionnaires that they had had a vasectomy previously;54 and men admitted to the hospital for elective operations, appendicitis, or injury.55 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 Table 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,53 vasectomy was associated with a significantly higher risk of diseases of the genitourinary system, including orchitis and epididymitis. A similar increased risk of orchitis/epididymitis was also seen in another large study.56 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 vasectomy53, 56 and to the possibility that men who had recently undergone vasectomy might be more likely to seek medical attention for nonvasectomy-related genitourinary conditions.53

In three of the studies,51, 52, 53, 54 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.

Walker53 and Petitti 54 and respective coworkers studied the risk of hospitalization separately in men with vasectomies of long duration—nine 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.11 Additional data on this cohort were later reported by Schuman and associates.12 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 eight years, ranging from 1 to 41 years. With the exception of epididymitis/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 colleagues16 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 associates:53 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 arthritis16 or the risk of hospitalization for arthritis11, 12, 53, 55 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, 2 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.57, 58

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.54, 59, 60, 61, 62 Taken together, the newer experimental studies in monkeys57, 58 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, Roberts63, 64 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.11, 12 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.65 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 coworkers66 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;67, 68 the other found that both were lower in vasectomized men than in nonvasectomized men.69 Verheught and associates measured serum cholesterol before and three months after vasectomy in 24 men and in a control group of 23 men of similar age.70 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.

IMMUNOLOGIC EFFECTS

An increased occurrence of circulating sperm-agglutinating antibodies in vasectomized men was first reported by Phadke and Padukone in 1964.4 Subsequently, numerous investigators have confirmed the presence of anti-sperm antibodies in association with vasectomy.5, 7, 8, 9, 10, 71, 72, 73

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 inflammation1
  • Vasectomized men may have immunity to tumor-associated antigens that could affect directly the development of tumors.74

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.6, 11, 53, 56, 61, 75, 76, 77 Anti-sperm antibodies may be associated with decreased fertility following vasectomy reversal (see chapter 'Reversing Vasectomy').

Antisperm Antibodies

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 barrier78 and leakage of sperm antigens from the epididymis.69 Sperm antigens have been found in the serum of men as early as two weeks after vasectomy.79

Antisperm antibodies are found in between 8% and 21% of men in the general population and in 9% and 36% of infertility patients.78 In contrast, circulating sperm agglutinating antibodies are found in 50–80% of men in the first year after vasectomy.4, 5, 6, 7, 8, 9, 10, 80 Approximately 3% of nonvasectomized men have sperm-immobilizing antibodies69 whereas anywhere from 25–60% of men develop sperm-immobilizing antibodies in the first year after vasectomy.7, 8, 9, 10 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.6, 81

Although serum anti-sperm antibodies are common following vasectomy, fewer men have these antibodies in their seminal plasma.82 Following surgery for vasectomy reversal, however, anti-sperm antibodies are more commonly found in seminal plasma78 and are found on the surface of sperm as well.78, 83

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.71, 72, 73, 84 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.71, 73

Large variations occur in the titers of both sperm-agglutinating and sperm-immobilizing antibodies in men following vasectomy.9, 69 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 investigators85, 86 reporting no change and others8, 69 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.69, 73 A family history of autoimmune disease is not associated with development of anti-sperm antibodies.73

Other Autoantibodies

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.10, 72, 73, 87, 88, 89, 90, 91, 92 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,93, 94 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.10, 95, 96

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.11, 12, 51, 52, 53, 54, 55, 56

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.97

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.87, 98, 99 One study demonstrated a higher incidence and higher levels of circulating immune complexes in men who were vasectomized for a mean of nearly eight years compared with those in age-matched controls.100 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 three months to one year after vasectomy.72, 73, 79, 92, 101 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.69

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.11, 12, 52, 54, 55, 102

PROSTATE CANCER

Incidence of prostate cancer is rising, and in the United States it is the most commonly diagnosed cancer among men.103 Although this may be due at least in part to enhanced screening and detection, these are unlikely to be the only factors involved.104 Little is known about the etiology and pathogenesis of prostate cancer, and few risk factors have been identified.105 Family history of prostate cancer appears to be an important risk106, 107 and incidence increases with age, varies with ethnicity, and shows wide geographic variation.108 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. The incidence of prostate cancer of American blacks, for example, is twice that of Zimbabwean blacks;109 in American whites the incidence of prostate cancer is twice that of European whites;108 and incidence of prostate cancer among Japanese immigrants in the United States is higher than among Japanese in Japan.110 Dietary fat intake may be an important risk factor.111, 112, 113

Over two 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: conflicting research findings have been reported; 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.114 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.115 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.116

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,117, 118 one reported a nonsignificantly increased risk,119 and the other two reported no increased risk.120, 121 Limitations, including detection and misclassification bias, were possible in all of these studies.122

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.123, 124 These studies provided the best evidence for a causal link between vasectomy and prostate cancer and prompted the US 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.125

Since that time, there have been 15 additional studies on vasectomy and prostate cancer published (Table 6). Thirteen showed no significant increased relative risk of prostate cancer in vasectomized men, confirming 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.126 Authors of two meta-analysis of published studies on vasectomy and prostate cancer concluded that numerous sources of bias may have led to an overestimation of any effect of vasectomy on prostate cancer.127, 128 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.129 The only reported study examining vasectomy reversal to protect against prostate cancer found a non-significant reduction in prostate cancer risk in vasectomized men who had a reversal compared to vasectomized men who had not had a reversal.130

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.125 Based on the available evidence, the American Urological Association states that it is no longer necessary to inform men of a possible risk of prostate cancer associated with vasectomy.131 

TESTICULAR CANCER

Table 7 summarizes results of epidemiologic studies of vasectomy and testicular cancer. With one exception,132 the studies conducted between the 1970s and early 1990s that showed an increased risk of testicular cancer following vasectomy were not statistically significant.51, 133, 134, 135 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,55, 116, 136 and Giovannucci and coworkers61 found no cases of testicular cancer among nearly 15,000 vasectomized men. Additional studies, which included the largest numbers of cases of testicular cancer among vasectomized men, found no increased risk.62, 137, 138, 139 Taken together, results of these epidemiologic studies provide convincing evidence that vasectomy is not associated with an increased risk of testicular cancer.

UROLITHIASIS

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.12, 16, 55 Kronmal and associates,140 examining data from the Coronary Artery Surgery Study registry, first reported a significantly increased risk of urolithiasis in vasectomized men in the late 1980s. Subsequently, 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.141 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.

CHRONIC TESTICULAR PAIN

Chronic testicular pain or discomfort (sometimes called postvasectomy pain syndrome) is reported by some men after vasectomy. While up to one-third to one-half of men have reported occasional testicular discomfort after vasectomy only a small percentage of all vasectomized men (no more than 2–3%) said the pain had negatively impacted their life or that they regretted having had the vasectomy because of chronic pain.38, 142, 143, 144, 145 There are limited data on chronic testicular pain in the general population and only one study of postvasectomy pain included a control group. In that study, 47% of vasectomized men reported having occasional testicular discomfort compared to 23% of controls, with 6% and 2%, respectively, seeking medical advice.146 None of the men reported they regretted having had a vasectomy because of the pain. The cause of chronic testicular pain after vasectomy is poorly understood, but may be related to infection, epididymal or vas congestion, back pressure-induced epididymal tubule rupture, sperm granuloma formation, or nerve entrapment.147, 148, 149, 150, 151 Conservative therapy such as nonsteroidal anti-inflammatory drugs, sitz baths, antibiotics, or spermatic cord blocks is sufficient treatment in most cases.150, 152 When this fails, there is some evidence that vasectomy reversal, epididymectomy or denervation of the spermatic cord may be helpful.147, 150, 152, 153 During counseling it is important to mention that a small percentage of men experience chronic testicular pain following vasectomy.

OVERALL MORTALITY RATES

Overall mortality rates in vasectomized and nonvasectomized men have been examined in three large cohort studies11, 12, 61, 154 and were 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.11, 61

CONCLUSIONS

There have now been over three 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.

Table 1. Studies of the effects of vasectomy on testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH)

Study

Time between vasectomy and last measure


No. of study subjects

 Results

Testosterone

LH

FSH

Longitudinal

Bunge (1972)155

1 mo

50

0

NM

NM

Wieland et al (1972)156

2 mo

8

0

0

0

Johnsonbaugh et al (1977)157 

3 mo

24

0

0

0

Glavind et al (1990)158

3 mo

51

NM

0

0

Tyler et al (1979)159

4 mo

~32

0

0

0

Nikkanen and Punnonen (1982)160       

6 mo

22

0

+

0

Kobrinsky et al (1976)161

4–40 mo

11

0

0

0

Fisch et al (1989)162

2–64 mo

25

0

0

0

Purvis et al (1976)163

1 yr

30

0

0

0

Naik et al (1976)164

1 yr

19

0

0

0

Whitby et al (1976)165

1 yr

39

0

+

0

Alexander et al (1980)3

1 yr

99

0

0

0

de la Torre et al (1983)166

2 yr

20

0

0

0

Smith et al (1976)167

2 yr

56

+

0

0

Rosenberg et al (1974)168

2 yr

13

NM

0

0

Johnsonbaugh et al (1975)169

2–2.5 yr

9

0

0

0

Goebelsmann et al (1979)170

2 yr

16

0

0

0

Smith et al (1979)171

3 yr

56

+

0

0

Whitby et al (1979)172

5 yr

54

0

0

NM

Cross-Sectional

Varma et al (1975)173

5 yr

81

0

0

0

Devi et al (1977)174

1–10 yr

180

0

0

0

Skegg et al (1976)175

6 mo–5 yr

188

0

0

0

Mo et al (1995)22

10–>20 yr

91

0*

0

0

Peng et al (1987)176

1–25 yr

505

0

0

0


* 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

Table 2. Summary of designs of four record-linkage studies of disease incidence in vasectomized men and comparison subjects

Study

Source of study subjects

No. and description of study subjects

Goldacre et al (1978, 1979)51, 52

Scottish Medical Record Linkage System

 

1,764 vasectomized men

16,641 men who had other operations

Walker et al (1981)53

Puget Sound Health Cooperative

 

6,092 vasectomized men

~70,000 other male members of plan

Petitti et al (1983)54

Northern California Kaiser-Permanente Medical Care Program


4,385 vasectomized men

13,155 age- and race-matched nonvasectomized men having routine medical checkups


Nienhuis et al (1992)55

Oxford Record Linkage Study

13,246 vasectomized men

 22,196 men admitted to the hospital for elective operations, or because of appendicitis, or injury


 

Table 3. Summary of results of three record-linkage studies of disease incidence in vasectomized men and comparison subject

International Classification of Disease, adapted 8th ed. (ICDA-8) Code


Description

Study

Number of cases in vasectomized men


Risk relative to vasectomized men (95% confidence interval*)


140–209

Malignant neoplasm

Scottish

9

0.6†

Puget Sound

31

1.0 (0.6–1.6)

Kaiser

21

0.8 (0.5–1.3)

210–228

Benign neoplasm

Scottish

4

0.6†

Puget Sound

34

1.5 (0.9–2.5)

Kaiser

6

0.9 (0.3–2.1)

240–279

Endocrine, nutritional, and metabolic diseases

 

Scottish

12

1.0†

Puget Sound

32

0.5 (0.3–0.8)

Kaiser

5

0.8 (0.3–2.1)

290–318

Mental disorders

Scottish

5

0.3†

Puget Sound

14

0.3 (0.1–0.5)

Kaiser

8

0.6 (0.3–1.4)

390–458

Diseases of the circulatory system

 

Scottish

76

1.0†

Puget Sound

111

0.8 (0.6–1.0)

Kaiser

77

1.1 (0.8–1.4)

460–519

Diseases of the respiratory system

 

Scottish

46

0.8†

Puget Sound

77

0.8 (0.6–1.0)

Kaiser

21

1.0 (0.6–1.7)

520–577

Diseases of the digestive system

 

Scottish

90

0.8†

Puget Sound

194

1.0 (0.9–1.3)

Kaiser

79

0.8 (0.6–1.0)

580–611

Diseases of the genitourinary system

 

Scottish

21

0.6†

Puget Sound

116

1.6 (1.2–2.0)

Kaiser

28

1.2 (0.8–1.9)

710–739

Diseases of the musculoskeletal system and connective tissue

 

 

Scottish

47

0.7†

Puget Sound

121

1.3 (1.0–1.6)

Kaiser

26

1.1 (0.7–1.7)


* 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 50–53)

 

Table 4. Summary of results of disease incidence in vasectomized men and comparison subjects from the Oxford Record Linkage Study

International Classification of Disease, 9th revision (ICDA-9) Code

Description

Number of cases in vasectomized men

Risk relative to vasectomized men (95% confidence interval*)


185

Prostate cancer

1

0.44 (0.1–4.0)

186

Testicular cancer

4

0.46 (0.1–1.4)

200–208

Lymphoma, leukemia

16

0.92 (0.5–1.7)

242

Thyrotoxicosis

4

1.17 (0.3–4.2)

401–405

Hypertension

33

0.86 (0.6–1.3)

410

Myocardial infarction

97

1.0 (0.8–1.3)

411–414

Other ischemic heart disease

41

0.55 (0.4–0.8)

430–438

Stroke

25

0.65 (0.4–1.0)

556

Ulcerative colitis

8

0.78 (0.3–1.8)

592, 594

Renal calculus

35

1.2 (0.8–1.8)

600

Prostatic hypertrophy

7

0.57 (0.5–1.7)

714

Rheumatoid arthritis

11

0.84 (0.4–1.7)


* 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)

 

Table 5. Summary of studies of vasectomy and cardiovascular disease


Authors

Study design

Study population

Endpoint

Number of cases with vasectomy or cardiac endpoint

Relative risk (95% confidence interval)

Guang-hua et al (1978)154

Retrospective cohort

5,761 vasectomized

Ischemic heart disease

NR

0.5 (0.3–0.7)

5,761 nonvasectomized

Stroke

NR

2 (0.6–6.6)

Goldacre et al (1978, 1979, 1983)51, 52, 75

Cohort

1,764 vasectomized

Myocardial infarction

25

No association of vasectomy with increased risk of any endpoint

16,641 nonvasectomized

 

Stroke

6

Hypertension

5

Cardiovascular disease as a group

36

Fahrenbach et al (1980)67

Cross-sectional

41 vasectomized

Hypertensive and atherosclerotic retinal vascular changes

NR

In men <40 years old, vasectomized men had more retinal vascular changes than controls. There was no difference in damage between vasectomized men and controls >40.

112 nonvasectomized

Walker et al (1981, 1983, 1981)53, 59, 177

Cohort

4,800 vasectomized

Acute myocardial infarction

21

0.8 (0.4–1.3)

24,000 nonvasectomized

Cardiovascular disease as a group

111

0.8 (0.6–1.0)

Wallace et al (1981)178

Case-control

55 cases

Symptomatic coronary disease

14

No association between vasectomy and coronary

55 close relative controls

Linnet et al (1982)101

Cross-sectional

46 vasectomized

Atherosclerotic retinal vascular change gradings between vasectomized men and controls

21

No difference in arteriolosclerotic retinopathy

46 nonvasectomized

Petitti et al (1982)16

Cross-sectional

4,385 vasectomized

History of myocardial infarction

158

1.0 (0.9–1.1)

13,155 nonvasectomized

Chest pain or pressure

553

1.1 (1.0–1.2)

Hypertension

702

1.0 (0.9–1.0)

Goldacre et al (1983)75

Case control

1,512 cases

Myocardial infarction

NR

1.1 (0.7–1.8)

3,024 controls

Stroke

NR

0.8 (0.4–1.9)

Hypertension

NR

0.4 (0.1–1.3)

Cardiovascular disease as a group

NR

0.9 (0.6–1.3)

Petitti et al (1983)54

Cohort

4,385 vasectomized

Myocardial infarction

23

1.2 (0.7–1.9)

13,155 nonvasectomized

Other ischemic heart disease

29

1.3 (0.8–1.9)

Cardiovascular disease as a group

47

1.3 (0.8–1.9)

Rimm et al (1983)102

Cross-sectional

370 vasectomized

Severity of angiographically diagnosed coronary artery disease

370*

Vasectomized men had significantly lower degree of coronary artery occlusion than age-matched controls

7,050 nonvasectomized

Perrin et al (1984)179

Cohort

1,383 vasectomized

Coronary disease

360

0.99 (0.84–1.17)

3,561 nonvasectomized

Rosenberg et al (1986)180

Case-control

2,238 cases

Myocardial infarction- all

332

1.0 (0.8–1.3)

3,361 controls

Myocardial infarction-15+ yrs

34

15+ yrs. 1.1 (0.7–2.0)

Chi et al (1990a)60

Case-control

163 cases

Nonfatal myocardial infarction

29

2.6 (1.1–6.1)

 

326 controls

Chi et al (1990b)181

Case-control

348 cases

Fatal cardiovascular disease (ischemic heart disease, nontraumatic cerebrovascular disease, hypertensive disease)

36

1.0 (0.4–2.4)

348 controls

Giovannucci et al (1992)61

Cohort

14,607 vasectomized

Fatal cardiovascular disease

253

0.8 (0.6–0.9)

14,607 nonvasectomized

Fatal and nonfatal cardiovascular disease combined

1206

0.97 (0.9–1.1)

Nienhuis et al (1992)55

Retrospective cohort

 

13,246 vasectomized

Myocardial infarction

97

1.0 (0.8–1.3)

22,196 nonvasectomized

Schuman et al (1993)12 & Massey et al (1984)11

Retrospective cohort

 

10,079 vasectomized

Myocardial infarction

540†

0.9 (0.8–1.2)

10,079 nonvasectomized

Angina

344†

1 (0.8–1.2)

Stroke

97†

0.8 (0.5–1.2)

Goldacre et al (2005)62

Retrospective cohort

 24,773 vasectomizedMyocardial infarction4440.96 (0.87–1.08)
 159,480 nonvasectomized Coronary heart disease7810.95 (0.88–1.02)
 Stroke1010.72 (0.58–0.88)

* 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

Table 6. Summary of studies of vasectomy and prostate cancer


Reference

Study design

Study population

Number of cases with vasectomy or prostate cancer

Estimated relative risk all durations (95% confidence interval)

Estimated relative risk long duration* (95% confidence interval)

Ross et al (1983)120

Case-control

110 matched case-control pairs

NR

0.5 (0.2–1.4)

NR

Honda et al (1988)119

Case-control

216 matched case-control pairs

58

1.4 (0.9–2.3)

30+ yr: 4.4 (0.9–21)

Mettlin et al (1990)117

Case-control

614 cases

27

1.7 (1.1–2.6)

19+ yr: 1.5 (0.7–3.4)

2,588 controls

Rosenberg et al (1990)114

Case-control

220 cases

22

 

Noncancer controls 5.3(2.7–10)

15+ yr: Noncancer controls 6.4 (NR)

571 noncancer controls

Cancer controls 3.5 (2.1–6.0)

 

15+ yr: Cancer controls 3.0 (NR)

 

960 cancer controls

Sidney et al (1991)182

Retrospective cohort

5,119 vasectomized

35

1.0 (0.7–1.6)

20+ yr: 1.2 (0.6–2.2)

15,357 matched controls

Spitz et al (1991)118

Case-control

343 cases

NR

1.6 (1.1–2.3)

27+ yr: 2.2 (1.1–4.3)

360 controls

Nienhuis et al (1992)55

Retrospective cohort

13,246 vasectomized

1

0.4 (0.1–4.0)

NR

22,196 nonvasectomized

Giovannucci et al (1993a)123

Prospective cohort

10,055 vasectomized

59

1.7 (1.3–2.2)

22+ yr: 1.9 (1.3–2.72)

37,800 nonvasectomized

Giovannucci et al (1993b)124

Retrospective cohort

13,034 vasectomized

54

1.6 (1.03–2.4)

20+ yr: 1.9 (1.1–3.1)

12,306 nonvasectomized

Schuman et al (1993)12

Retrospective cohort

10,079 vasectomized

6

No increased incidence of disease in vasectomized men compared with controls

NR

 

10,079 nonvasectomized

Hayes et al (1993)183

Case-control

Blacks: 471 cases, 589 controls

Blacks: 7

Blacks 1.6 (0.5–4.8)

Blacks: 20+ yr: 1.2 (0.2–6.4)

Whites: 494 cases, 703 controls

Whites: 49

Whites 1.1 (0.8–1.7)

Whites: 20+ yr: 1.7 (0.8–3.3)

Rosenberg et al (1994)116

Case-control

355 cases

18

1.2 (0.6–2.7)

15+ yr: 1.4 (0.5–4.2)

2,048 controls

Moller et al (1994)137

Retrospective cohort

Cancer incidence in 73,917 vasectomized men compared to the Danish population

12

0.94 (0.5–1.7)

NR

Hsing et al (1994)184

Case-control

136 cases

14

Cancer: 2.0 (0.7–6.1)

NR

 

158 hospital cancer controls

Noncancer: 3.3 (1.0–11.3)

158 hospital noncancer controls

Neighborhood: 6.7 (2.1–21.6)

322 neighborhood controls

John et al (1995)185

Case-control

1,624 cases

172

1.1 (0.8–1.4)

NR

1,636 controls

Zhu et al (1996)186

Case-control

175 cases

61

0.86 (0.6–1.3)

20+ yr: 0.8 (0.5–1.4)

258 controls

Platz et al (1997)187

Case-control

175 cases

17

1.5 (0.8–2.7)

20+ yr: 1.6 (0.8–3.1)

978 controls

Stanford et al (1999)188Case-control753 cases 2971.1 (0.9–1.4) NR
703 controls
Lesko et al (1999)189Case-control1,216 cases2001.0 (0.8–1.3)NR
1,400 controls
Chacko et al (2002)190Prospective cohort

101 vasectomized

46 No increased risk of prostate cancer in vasectomized men NR
202 nonvasectomized
Cox et al (2002)191Case-control923 cases 2160.92 (0.75–1.14)25+ yr: 0.92 (0.68–1.23)
1224 controls
Lynge 2002)139Retrospective cohortProstate cancer incidence in 57,931 vasectomized men compared to the Danish population460.98 (0.7–1.3)NR
Rohrmann et al (2005)192Prospective cohort918 vasectomized27 2.03 (1.24–3.32)NR
2455 nonvasectomized
Goldacre et al (2005)62

Retrospective cohort

24,773 vasectomized 21 0.74 (0.45–1.14)NR
159,480 nonvasectomized

* Number of years postvasectomy.
NR, not reported.

Table 7. Summary of studies of vasectomy and testicular cancer

Authors

Study design

Study population

Number of cases with vasectomy or testicular cancer

Relative risk (95% of confidence interval)

Goldacre et al (1978)51

Retrospective cohort

1,764 vasectomized

1

2.1 (0.1–11.6)

16,641 nonvasectomized

Moss et al (1986)136

Case-control

273 age-matched, case-control pairs

15

0.6 (0.3–1.2)

Swerdlow et al (1987)133

Case-control

259 cases

22

1.1 (0.6–2.0)

489 controls

Strader et al (1988)134

Case-control

333 cases

46

1.5 (1.0–2.2)

729 controls

Thornhill et al (1988)135

Case-control

240 cases

3

3.8 (0.8–11)

23,148 vasectomy man-years

Cale et al (1990)132

Retrospective cohort

Cancer incidence in 3,079 vasectomized men compared with national rates

8

4.2 (1.8–8.2)

Nienhuis et al (1992)55

Retrospective cohort

13,246 vasectomized

4

0.5 (0.1–1.4)

22,196 nonvasectomized

Giovannucci et al (1992)61

Retrospective cohort

14,607 vasectomized

0

NR

14,607 nonvasectomized

Schuman et al (1993)12

Retrospective cohort

10,079 vasectomized

6

No increased incidence of disease in vasectomized men compared with controls

10,079 nonvasectomized

Rosenberg et al (1994)116

Case-control

132 cases

7

0.8 (0.4–1.9)

7,027 controls

UK Testicular Cancer Group (1994)138

Case-control

794 age-matched, case-control pairs

 

81

1.09 (0.8–1.5)

Moller et al (1994)137

Retrospective cohort

Testicular cancer incidence in 73,917 vasectomized men compared with the Danish general population

701.0 (0.8–1.3)
Lynge (2002)139Retrospective cohort

Testicular cancer incidence in 57,931 vasectomized men compared to the Danish population

97 0.98 (0.76-1.13)
Goldacre et al (2005)62Retrospective cohort 

24,773 vasectomized 

110.65 (0.31-1.21)

159,480 nonvasectomized 

 NR, not reported.

Table 8. Summary of studies of vasectomy and urolithiasis

Authors

Study design

Study population

Number of cases with vasectomy or urolithiasis

Relative risk (95% confidence interval)

Petitti et al (1982)16

Cross-sectional

4,385 vasectomized

215

1.2 (1.0–1.4)

13,155 nonvasectomized

Kronmal et al (1988)140

Retrospective cohort

1,106 vasectomized

NR

1.7 (1.3–2.3)

10,099 nonvasectomized

Nienhuis et al (1992)55

Retrospective cohort

13,246 vasectomized

94

1.1 (0.7–1.9)

22,196 nonvasectomized

Schuman et al (1993)12

Retrospective cohort

10,079 vasectomized

268

No increased incidence of disease in vasectomized men compared with controls

 

10,079 nonvasectomized

Kronmal et al (1997)141

Case-control

244 cases

91

<46 yr old: 1.9 (1.2–3.1)

46+ yr old: 0.9 (0.5–1.5)

463 controls


NR, not reported.

Table 9. Summary of studies examining total mortality in vasectomized and nonvasectomized men


ReferenceStudy designStudy population

Number of deaths in vasectomized men

Relative risk (95% confidence interval)

Guang-hua et al (1978)154

Retrospective cohort

5,761 vasectomized

137

0.8 (0.7–0.9)

5,761 nonvasectomized

Schuman et al (1993)12 & Massey et al (1984)11

 

Retrospective cohort

10,079 vasectomized

538*

0.8 (0.7–0.9)

10,079 nonvasectomized

Giovannucci et al (1992)61

Retrospective cohort

14,607 vasectomized

1,052*

0.9 (0.8–1)

14,607 nonvasectomized


* Total deaths among all men in cohort.

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