This chapter should be cited as follows:
Barone, M, Achola, J, Glob. libr. women's med.,
(ISSN: 1756-2228) 2015; DOI 10.3843/GLOWM.10409
This chapter was last updated:
May 2015

Long-Term Risks of Vasectomy

Mark A. Barone, DVM, MS
EngenderHealth, New York, New York, USA
Japhet Ominde Achola, MBCHB, MMed
EngenderHealth, Nairobi, Kenya

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 could 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 nearly four decades, however, provide little evidence of any significant long-term side effects of vasectomy. Current guidelines from the American Urological Association11 and the European Association of Urology12 reflect this in their recommendation for preoperative counselling for men/couples considering vasectomy (see Box 1). Nonetheless, the topic remains of considerable interest with reports of studies on the topic appearing regularly in the scientific literature.

Box 1 Vasectomy counselling recommendations related to long-term risks following vasectomy11, 12







 

 

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.13, 14, 15 In a large cohort study,16, 17 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.18, 19, 20, 13, 14, 15 In one large study, the number of men reporting loss of sexual interest was identical in vasectomized versus nonvasectomized men.21

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; sperm are broken down by macrophages in the lumen of the epididymal tubule.4, 22 Sometimes the blockage in the reproductive tract after vasectomy causes pressure to build up in the epididymis, which leads to distension in the tubules 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. Some vasectomy providers believe that this buildup can be avoided by leaving open the testicular end of the vas.

ENDOCRINE/HORMONAL EFFECTS

Although some early prospective 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 within the normal range for adults.23 Studies in animals suggesting an effect of vasectomy on testicular weight and Leydig cell morphology, which were never confirmed,24, 25, 26 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.

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)27

1 month

50

0

NM

NM

Wieland et al (1972)28

2 months

8

0

0

0

Johnsonbaugh et al (1977)29 

3 months

24

0

0

0

Glavind et al (1990)30

3 months

51

NM

0

0

Tyler et al (1979)31

4 months

~32

0

0

0

Nikkanen and Punnonen (1982)32       

6 months

22

0

+

0

Kobrinsky et al (1976)33

4–40 months

11

0

0

0

Fisch et al (1989)34

2–64 months

25

0

0

0

Purvis et al (1976)35

1 year

30

0

0

0

Naik et al (1976)36

1 year

19

0

0

0

Whitby et al (1976)37

1 year

39

0

+

0

Alexander et al (1980)3

1 year

99

0

0

0

de la Torre et al (1983)38

2 years

20

0

0

0

Smith et al (1976)39

2 years

56

+

0

0

Rosenberg et al (1974)40

2 years

13

NM

0

0

Johnsonbaugh et al (1975)41

2–2.5 years

9

0

0

0

Goebelsmann et al (1979)42

2 years

16

0

0

0

Smith et al (1979)43

3 years

56

+

0

0

Whitby et al (1979)44

5 years

54

0

0

NM

Cross-sectional

Varma et al (1975)45

5 years

81

0

0

0

Devi et al (1977)46

1–10 years

180

0

0

0

Skegg et al (1976)47

6 months–5 years

188

0

0

0

Mo et al (1995)48

10–>20 years

91

0*

0

0

Peng et al (1987)49

1–25 years

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

 

In nearly all longitudinal studies and all of the cross-sectional studies (with the exception of that of Mo and colleagues,48 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

Histological and morphometric examination of seminiferous tubules and testes of vasectomized men showed that some of the normal ultrastructure was maintained.50, 51, 52, 53 For example:

  • the blood supply to the tubules was intact
  • seminiferous tubules were normal in terms of patency, diameter and basement membrane
  • Sertoli cells appeared to be intact and
  • the normal stages of spermatogenesis were evident.

Histological 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,50 increased thickness of the seminiferous tubular walls,26, 54, 55, 56 reduced number of spermatids,54, 56, 57 increased focal interstitial fibrosis,26, 52, 54, 55, 56 and decreased numbers of sperm/gram of testis.56

How these changes occur and their significance remain unclear.

Some men with these changes have been able to produce offspring following vasectomy reversal58, 54, 59 or assisted reproduction.56 In one study in which fertility was examined in relation to histologic changes, interstitial fibrosis was significantly correlated with infertility in men 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.54 Long-term spermatogenic damage has not been seen in men up to 39 years after vasectomy and there is no increase in sperm aneuploidy (an abnormal number of chromosomes) following vasectomy.50, 52, 53

.

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.60 The mechanism whereby sperm can be accommodated in the human epididymis following vasectomy 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.60

Epididymitis (inflammation of the epididymis often accompanied by swelling and pain) in vasectomized men has been referred to as 'congestive' epididymitis. It is rarely of infectious origin, instead it is caused by distension of the epididymis owing to continued passage of sperm from the testis into the epididymis with no outflow given the occluded vas.61, 62, 63 Epididymitis following vasectomy is uncommon, with most studies reporting rates of approximately 1–3% of men who have had a vasectomy, but rarely have unvasectomized controls been included in these studies.11

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.64, 65, 66 Ultrasound studies have found that epididymal enlargement is common and may not be associated with any pain or discomfort.67, 68 On ultrasound examination, vasectomized men had a significantly higher incidence of thickened epididymides, epididymal tubular ectasia (when the normally invisible epididymal tubules are visible), sperm granulomas and mobile echogenicities (thought to be clumps of sperm trapped within dilated epididymal tubules) compared to non-vasectomized controls.69, 70 Histological changes have also been noted.71, 72, 73, 74 It is unclear if these changes are clinically significant.69

The epididymis plays a critical role in sperm maturation; it is during transit through the epididymis that sperm gain their full fertilizing potential.75 Vasectomy has been shown to affect gene expression and the synthesis of various proteins in the human epididymis, alterations that in some cases appear irreversible following vasovasestomy (i.e. reanastomosis of the cut ends of the vas).73, 76, 77 Some of these proteins may play a critical role in sperm maturation and may be responsible, at least in part, for the fact that pregnancy rates following vasovasestomy are consistently lower than rates of appearance of sperm in the ejaculate after vasectomy reversal (see Vasectomy Reversal chapter).

 

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.78 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.79

However, total prostatic volume and growth rate do not appear to be affected by vasectomy.80 Postvasectomy prostate-specific antigen levels have been significantly lower than preoperative levels for up to 6 months after vasectomy.81

The 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 semen as free-floating virus, HIV infected seminal white blood cells (WBCs), and in association with sperm, with all three potentially playing an important role in the sexual transmission of HIV.82, 83, 84, 85, 86, 87, 88, 89 

Preliminary data from Anderson and coworkers indicated that infectious HIV could be found in semen from some HIV seropositive vasectomized men.90 Subsequently, 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.91 Additionally, although the exact origin of the cell-free HIV and HIV infected WBCs in semen is unclear, it appears that HIV in the ejaculate arises from prostatic and seminal vesicle secretions, as well as the urethra.89, 92 Taken together, these results provide good evidence that vasectomy provides no protection against HIV transmission. This underscores the importance of counselling vasectomized men that vasectomy does not provide any protection against transmission or acquisition of HIV and other sexually transmitted infections (STIs) and that men need to use condoms consistently and correctly if they are at risk of transmitting or acquiring HIV/STIs.

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.93, 94, 95, 96, 97 In each, investigators identified retrospectively a group of men who were known to have had 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;93, 94 men with the same prepaid medical care program;95 men having routine health checkups who did not indicate on questionnaires that they had had a vasectomy previously;96 and men admitted to the hospital for elective operations, appendicitis, or injury.97 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.

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)93, 94

Scottish Medical Record Linkage System

 

1764 vasectomized men

16,641 men who had other operations

Walker et al (1981)95

Puget Sound Health Cooperative

 

6092 vasectomized men

~70,000 other male members of plan

Petitti et al (1983)96

Northern California Kaiser-Permanente Medical Care Program


4385 vasectomized men

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


Nienhuis et al (1992)97

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. Adapted from references 93, 94, 95, 96

International Classification of Disease, adapted 8th edn. (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)

*Scottish,93, 94 Puget Sound,95 Kaiser96

**Where given
†Ratio of standardized first-event rate in vasectomized men to average of standardized first-event rates in the three comparison groups

 

Table 4. Summary of results of disease incidence in vasectomized men and comparison subjects from the Oxford Record Linkage Study. Adapted from Nienhuis et al. Incidence of disease after vasectomy: A record linkage retrospective cohort study. BMJ 304;743, 199297

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.

 

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,95 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.98 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 vasectomy95, 98 and to the possibility that men who had recently undergone vasectomy might be more likely to seek medical attention for nonvasectomy-related genitourinary conditions.95

In three of the studies,93, 94, 95, 96 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.

Walker95 and Petitti 96 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 a 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.16 Additional data on this cohort were later reported by Schuman and associates.17 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 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 colleagues21 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 4385 vasectomized and 13,155 nonvasectomized men enrolled in the Kaiser-Permanente Medical Care Plan in the US. 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:95 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 arthritis21 or the risk of hospitalization for arthritis16, 17, 95, 97 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.99, 100

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.96, 101, 102, 103, 104 Taken together, the experimental studies in monkeys99, 100 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.

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)105

Retrospective cohort

5761 vasectomized

Ischemic heart disease

NR

0.5 (0.3–0.7)

5761 nonvasectomized

Stroke

NR

2 (0.6–6.6)

Goldacre et al (1978, 1979, 1983)93, 94, 106

Cohort

1764 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)107

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)95, 101, 108

Cohort

4800 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)109

Case–control

55 cases

Symptomatic coronary disease

14

No association between vasectomy and coronary

55 close relative controls

Linnet et al (1982)110

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)21

Cross-sectional

4385 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)106

Case–control

1512 cases

Myocardial infarction

NR

1.1 (0.7–1.8)

3024 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)96

Cohort

4385 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)111

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

7050 nonvasectomized

Perrin et al (1984)112

Cohort

1383 vasectomized

Coronary disease

360

0.99 (0.84–1.17)

3561 nonvasectomized

Rosenberg et al (1986)113

Case–control

2238 cases

Myocardial infarction- all

332

1.0 (0.8–1.3)

3361 controls

Myocardial infarction-15+ years

34

15+ years 1.1 (0.7–2.0)

Chi et al (1990a)102

Case–control

163 cases

Nonfatal myocardial infarction

29

2.6 (1.1–6.1)

 

326 controls

Chi et al (1990b)114

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)103

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)97

Retrospective cohort

 

13,246 vasectomized

Myocardial infarction

97

1.0 (0.8–1.3)

22,196 nonvasectomized

Schuman et al (1993)17 & Massey et al (1984)16

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)104

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

 

VARIOUS PHYSIOLOGIC EFFECTS

In the late 1960s and the early 1970s, Roberts115, 116 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.16, 17 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.117 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 coworkers118 used information from comprehensive multiphasic health checkups in 4385 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 mmHg) 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;107, 119 the other found that both were lower in vasectomized men than in nonvasectomized men.120 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.121 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, 122, 123, 124

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.125

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, 16, 95, 98, 103, 106, 126, 127 Anti-sperm antibodies may be associated with decreased fertility following vasectomy reversal (see chapter 'Reversing Vasectomy').

Anti-sperm 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 barrier128 and leakage of sperm antigens from the epididymis.120 Sperm antigens have been found in the serum of men as early as 2 weeks after vasectomy.129

Anti-sperm antibodies are found in between 8% and 21% of men in the general population and in 9% and 36% of infertility patients.128 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, 130 Approximately 3% of nonvasectomized men have sperm-immobilizing antibodies,120 whereas anywhere from 25 to 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 develop them in the second or third year after the procedure.6, 131

Although serum anti-sperm antibodies are common following vasectomy, fewer men have these antibodies in their seminal plasma.132 Following surgery for vasectomy reversal, however, anti-sperm antibodies are more commonly found in seminal plasma128 and are found on the surface of sperm as well.128, 133

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.122, 123, 124, 134 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.122, 124

Large variations occur in the titers of both sperm-agglutinating and sperm-immobilizing antibodies in men following vasectomy.9, 120 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 investigators135, 136 reporting no change and others8, 120 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 antisperm antibodies.120, 124 A family history of autoimmune disease is not associated with development of anti-sperm antibodies.124

One small case–control study reported that vasectomy may be a risk factor for dementia (specifically primary progressive aphasia).137 The authors suggested that this increased risk could be related to the presence of anti-sperm antibodies following vasectomy, with the anti-sperm antibodies somehow affecting the brain because sperm share antigenic epitopes with brain tissue. Unfortunately, anti-sperm antibody levels were not measured in that study population. Results of a subsequent small study found no association between anti-sperm antibodies and Alzheimer’s disease, another form of dementia.138 Additionally, no increases in any mental disorders were reported in three large epidemiologic studies.93, 94, 95, 96 Selection bias, misclassification of data and confounding may have contributed to the reported relationship between anti-sperm antibodies and primary progressive aphasia.139    

  

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-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, 123, 124, 140, 141, 142, 143, 144, 145 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,146, 147 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, 148, 149

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.16, 17, 93, 94, 95, 96, 97, 98

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.150

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.140, 151, 152 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.153 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.123, 124, 129, 145, 110 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.120

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.16, 17, 94, 96, 97, 111

PROSTATE CANCER

Globally, prostate cancer is the second most common cause of cancer in men.154 In the United States it is the most commonly diagnosed cancer among men; twice as common in 2013 as the next leading cause (lung and bronchus cancer).155 Little is known about the etiology and pathogenesis of prostate cancer, with the only well-defined risk factors being family history of prostate cancer,  increasing age, and black ethnicity.156 Black men appear to be more susceptible to prostate cancer due to genetic factors, but data suggest that other factors such as diet and socioeconomic status also play a role, with incidence rates among black men varying from one country to another.157

Almost 30 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).

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)158

Case–control

110 matched case–control pairs

NR

0.5 (0.2–1.4)

NR

Honda et al (1988)159

Case–control

216 matched case–control pairs

58

1.4 (0.9–2.3)

30+ years: 4.4 (0.9–21)

Mettlin et al (1990)160

Case–control

614 cases

27

1.7 (1.1–2.6)

19+ years: 1.5 (0.7–3.4)

2588 controls

Rosenberg et al (1990)161

Case–control

220 cases

22

Noncancer controls 5.3(2.7–10)

15+ years: Noncancer controls 6.4 (NR)

571 noncancer controls

Cancer controls 3.5 (2.1–6.0)

15+ years: Cancer controls 3.0 (NR)

960 cancer controls

Sidney et al (1991)162

Retrospective cohort

5119 vasectomized

35

1.0 (0.7–1.6)

20+ years: 1.2 (0.6–2.2)

15,357 matched controls

Spitz et al (1991)163

Case–control

343 cases

NR

1.6 (1.1–2.3)

27+ years: 2.2 (1.1–4.3)

360 controls

Nienhuis et al (1992)97

Retrospective cohort

13,246 vasectomized

1

0.4 (0.1–4.0)

NR

22,196 nonvasectomized

Giovannucci et al (1993a)164

Prospective cohort

10,055 vasectomized

59

1.7 (1.3–2.2)

22+ years: 1.9 (1.3–2.72)

37,800 nonvasectomized

Giovannucci et al (1993b)165

Retrospective cohort

13,034 vasectomized

54

1.6 (1.03–2.4)

20+ years: 1.9 (1.1–3.1)

12,306 nonvasectomized

Schuman et al (1993)17

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)166

Case–control

Blacks: 471 cases, 589 controls

Blacks: 7

Blacks 1.6 (0.5–4.8)

Blacks: 20+ years: 1.2 (0.2–6.4)

Whites: 494 cases, 703 controls

Whites: 49

Whites 1.1 (0.8–1.7)

Whites: 20+ years: 1.7 (0.8–3.3)

Rosenberg et al (1994)167

Case–control

355 cases

18

1.2 (0.6–2.7)

15+ years: 1.4 (0.5–4.2)

2048 controls

Moller et al (1994)168

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)169

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)170

Case–control

1624 cases

172

1.1 (0.8–1.4)

NR

1636 controls

Zhu et al (1996)171

Case–control

175 cases

61

0.86 (0.6–1.3)

20+ years: 0.8 (0.5–1.4)

258 controls

Platz et al (1997)172

Case–control

175 cases

17

1.5 (0.8–2.7)

20+ years: 1.6 (0.8–3.1)

978 controls

Stanford et al (1999)173 Case–control 753 cases  297 1.1 (0.9–1.4)  NR
703 controls
Lesko et al (1999)174 Case–control 1216 cases 200 1.0 (0.8–1.3) NR
1400 controls
Chacko et al (2002)175 Prospective cohort

101 vasectomized

46  No increased risk of prostate cancer in vasectomized men  NR
202 nonvasectomized
Cox et al (2002)176 Case–control 923 cases  216 0.92 (0.75–1.14) 25+ years: 0.92 (0.68–1.23)
1224 controls
Lynge 2002)177 Retrospective cohort Prostate cancer incidence in 57,931 vasectomized men compared to the Danish population 46 0.98 (0.7–1.3) NR
Rohrmann et al (2005)178 Prospective cohort 918 vasectomized 27  2.03 (1.24–3.32) NR
2455 nonvasectomized
Goldacre et al (2005)104

Retrospective cohort

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

Holt et al (2008)179

Case–control

1001cases

362

1.0 (0.8–1.2)

20–24 years: 1.1 (0.7–1.7)

25–29 years: 1.1 (0.8–1.6)

30–34 years: 0.9 (0.6–1.2)

35+ years: 0.7 (0.5–1.1)

942 controls

Schwingl et al (2009)180

Case–control

294 cases

34

1.21 (0.79–1.87)

20–29 years: 1.21 (0.65–2.25)

≥30 years: 1.39 (0.74–2.62)

879 controls

Ahmadi et al (2011)181

Case–control

194 cases

15

Vasectomy status did not differ between cases and controls (p = 0.3)

NR

317 controls

Siddiqui et al (2014)

Prospective cohort

12,321

Total: 1,524

High-grade: 188

Lethal: 167

Total: 1.10 (1.04–1.17)

High-grade: 1.22 (1.03–1.45)

Lethal: 1.19 (1.00–1.43)

Total: ≥23 years: 1.10 (1.02–1.17)

37,084

*Number of years postvasectomy.
NR, not reported.

In 1990, there was a report of a case–control study showing a three- to sixfold increased risk of prostate cancer in vasectomized men.161 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 owing to the potential for various forms of bias.182 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.167

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,160, 163 one reported a nonsignificant increased risk,159 and the other two reported no increased risk.158, 183 Limitations, including detection and misclassification bias, were possible in all of these studies.184

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.164, 165 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.185

Since that time, there have been 19 additional studies on vasectomy and prostate cancer published (Table 6). Sixteen 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.186 Recently results of long-term (24 years) follow-up of the cohort first described by Giovannucci164 in 1993 were published.187 The authors reported that while vasectomy was not significantly associated with risk of low-grade prostate cancer, vasectomized men were at an increased risk of high-grade (Gleason score 8–10) and lethal prostate cancer (see Table 6).

Authors of two meta-analyses 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.188, 189 More recently, as part of the process of updating their vasectomy guidelines, the American Urological Association (AUA) performed a meta-analysis of 10 comparative cohort studies and found that there was no statistically significant difference in relative risk of prostate cancer in vasectomized men compared to men without a vasectomy and no relationship between time since vasectomy or age at time of vasectomy and prostate cancer. (Sharlip et al 2010). None of these three meta-analyses included the recently published Siddiqui article (Siddiqui et al 2014),187 although they did include the article describing the earlier findings from this cohort.164 The analysis of the long-term follow-up has the same potential for confounding, information and selection bias that the original analysis had and the authors note that the relative risk of lethal prostate cancer translates into a small increase in absolute risk. (Siddiqui et al 2014).187 

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.190 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.191

Studies published since the 1993 NIH expert panel  support the conclusions of that 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.185 Based on the available evidence, the latest AUA guidance is that it is not necessary to inform men of a possible risk of prostate cancer associated with vasectomy.11 While not specifically addressing prostate cancer, the current European Association of Urology guidelines recommend that prospective vasectomy clients should be told that available data indicate that vasectomy is safe and is not associated with any diseases.12

TESTICULAR CANCER

Table 7 summarizes results of epidemiologic studies of vasectomy and testicular cancer. With one exception,192 the studies conducted between the 1970s and early 1990s that showed an increased risk of testicular cancer following vasectomy was not statistically significant.93, 193, 194, 195 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,97, 167, 196 and Giovannucci and coworkers103 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.104, 168, 197, 177 Taken together, results of these epidemiologic studies provide convincing evidence that vasectomy is not associated with an increased risk of testicular cancer.

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)93

Retrospective cohort

1764 vasectomized

1

2.1 (0.1–11.6)

16,641 nonvasectomized

Moss et al (1986)196

Case–control

273 age-matched, case-control pairs

15

0.6 (0.3–1.2)

Swerdlow et al (1987)193

Case–control

259 cases

22

1.1 (0.6–2.0)

489 controls

Strader et al (1988)194

Case–control

333 cases

46

1.5 (1.0–2.2)

729 controls

Thornhill et al (1988)195

Case–control

240 cases

3

3.8 (0.8–11)

23,148 vasectomy man-years

Cale et al (1990)192

Retrospective cohort

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

8

4.2 (1.8–8.2)

Nienhuis et al (1992)97

Retrospective cohort

13,246 vasectomized

4

0.5 (0.1–1.4)

22,196 nonvasectomized

Giovannucci et al (1992)103

Retrospective cohort

14,607 vasectomized

0

NR

14,607 nonvasectomized

Schuman et al (1993)17

Retrospective cohort

10,079 vasectomized

6

No increased incidence of disease in vasectomized men compared with controls

10,079 nonvasectomized

Rosenberg et al (1994)167

Case–control

132 cases

7

0.8 (0.4–1.9)

7027 controls

UK Testicular Cancer Group (1994)197

Case–control

794 age-matched, case-control pairs

 

81

1.09 (0.8–1.5)

Moller et al (1994)168

Retrospective cohort

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

701.0 (0.8–1.3)
Lynge (2002)177Retrospective 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)104Retrospective cohort 

24,773 vasectomized 

110.65 (0.31-1.21)

159,480 nonvasectomized 

NR, not reported.

 

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.17, 21, 97 Kronmal and associates,198 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.199 The mechanism by which vasectomy might increase the risk of urolithiasis is unclear. The public health impact of an increase in the risk of urolithiasis of the magnitude suggested in the accumulated studies to date is small.

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)21

Cross-sectional

4385 vasectomized

215

1.2 (1.0–1.4)

13,155 nonvasectomized

Kronmal et al (1988)198

Retrospective cohort

1106 vasectomized

NR

1.7 (1.3–2.3)

10,099 nonvasectomized

Nienhuis et al (1992)97

Retrospective cohort

13,246 vasectomized

94

1.1 (0.7–1.9)

22,196 nonvasectomized

Schuman et al (1993)17

Retrospective cohort

10,079 vasectomized

268

No increased incidence of disease in vasectomized men compared with controls

 

10,079 nonvasectomized

Kronmal et al (1997)199

Case–control

244 cases

91

<46 years old: 1.9 (1.2–3.1)

46+ yeasr old: 0.9 (0.5–1.5)

463 controls


NR, not reported.

 

CHRONIC SCROTAL PAIN

Chronic scrotal 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 scrotal 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.68, 200, 201, 202, 203 There are limited data on chronic scrotal 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.204 At nearly 4 years of follow-up, 6% of vasectomized men had pain severe enough to seek medical advice compared to 2% of the men without a vasectomy. None of the vasectomized men in the study reported that they regretted having had a vasectomy because of the pain.

The cause of chronic scrotal pain after vasectomy is poorly understood, but may be related to infection, epididymal or vas congestion, back pressure-induced epididymal tubule rupture with subsequent interstitial fibrosis, sperm granuloma formation, or nerve entrapment.68, 205, 206, 207, 208, 209, 210 Conservative therapy such as nonsteroidal anti-inflammatory drugs, sitz baths, antibiotics, or spermatic cord nerve blocks is sufficient treatment in most cases.208, 211, 210 When these fail, vasectomy reversal, epididymectomy, denervation of the spermatic cord, or excision of sperm granuloma may be helpful.205, 208, 211, 212, 210 Most published reports of surgical therapy for chronic scrotal pain following vasectomy involve epididymectomy213, 214, 215, 216, 217 or vasectomy reversal,205, 218, 219, 220, 221 with results suggesting that they can be effective treatments for appropriately selected individuals in cases that are not resolved with more conservative measures.  

During counselling it is important to mention that a small percentage of men experience chronic testicular pain following vasectomy. The latest AUA guidelines recommend that providers include the following statement in their preoperative counselling: “Chronic scrotal pain associated with negative impact on quality of life occurs after vasectomy in about 1–2% of men. Few of these men require additional surgery.”11 

OVERALL MORTALITY RATES

Overall mortality rates in vasectomized and nonvasectomized men have been examined in three large cohort studies16, 17, 103, 105 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.16, 103

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)105

Retrospective cohort

5761 vasectomized

137

0.8 (0.7–0.9)

5761 nonvasectomized

Schuman et al (1993)17 & Massey et al (1984)16

 

Retrospective cohort

10,079 vasectomized

538*

0.8 (0.7–0.9)

10,079 nonvasectomized

Giovannucci et al (1992)103

Retrospective cohort

14,607 vasectomized

1,052*

0.9 (0.8–1)

14,607 nonvasectomized

* Total deaths among all men in cohort.

 

CONCLUSIONS

There have now been nearly four 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.222  Vasectomy appears to be a 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.

REFERENCES

1

Alexander NJ, Clarkson TB: Vasectomy increases the severity of diet-induced atherosclerosis in Macaca fascicularis. Science 201: 538, 1978

 

2

Clarkson TB, Alexander NJ: Long-term vasectomy: Effects on the occurrence and extent of atherosclerosis in rhesus monkeys. J Clin Invest 65: 15, 1980

 

3

Alexander NJ, Free MJ, Paulsen CA et al: A comparison of blood chemistry, reproductive hormones, and the development of antisperm antibodies after vasectomy in man. J Androl 1: 40, 1980

 

4

Phadke AM, Padukone K: Presence and significance of autoantibodies against spermatozoa in the blood of men with obstructed vas deferens. J Reprod Fertil 7: 163, 1964

 

5

Zappi E, Ahmed U, David J et al: Immunologic consequences of vasectomy. Fed Proc 29: 374, 1970

 

6

Shulman S, Zappi E, Ahmed U et al: Immunologic consequences of vasectomy. Contraception 5: 269, 1972

 

7

Ansbacher R: Sperm-agglutinating and sperm-immobilizing antibodies in vasectomized men. Fertil Steril 22: 629, 1971

 

8

Gupta I, Dhawan S, Goel GD et al: Low fertility rate in vasovasostomized males and its possible immunologic mechanism. Int J Fertil 20: 183, 1975

 

9

Hellema HWJ, Rumke P: Sperm autoantibodies as a consequence of vasectomy: I. Within 1 year post-operation. Clin Exp Immunol 31: 18, 1978

 

10

Bernstein GS, Chopp R, Cosgrove M et al: A controlled, prospective study of the effects of vasectomy. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p 473. New York: Academic Press, 1979

 

11

Sharlip ID, Belker AM, Honig S, Labrecque M, Marmar JL, Ross LS, Sandlow JI, Sokal DC; American Urological Association. Vasectomy: AUA guideline.J Urol. 2012 Dec;188(6 Suppl):2482-91

 

12

Dohle GR, Diemer T, Kopa Z, Krausz C, Giwercman A, Jungwirth A; European Association of Urology Working Group on Male Infertility. European Association of Urology guidelines on vasectomy. Eur Urol. 2012 Jan;61(1):159-63.

 

13

Arratia-Maqueo JA, Cortés-González JR, Garza-Cortés R, Gómez-Guerra LS. Evaluation of male sexual satisfaction after vasectomy. Actas Urol Esp. 2010 Nov;34(10):870-3.

 

14

Bertero E1, Hallak J, Gromatzky C, Lucon AM, Arap S. Assessment of sexual function in patients undergoing vasectomy using the international index of erectile function. Int Braz J Urol. 2005 Sep-Oct;31(5):452-8.

 

15

Smith A, Lyons A, Ferris J, Richters J, Pitts M, Shelley J. Are sexual problems more common in men who have had a vasectomy? A population-based study of Australian men. J Sex Med. 2010 Feb;7(2 Pt 1):736-42.

 

16

Massey FJ Jr, Bernstein GS, O'Fallon WM et al: Vasectomy and health: Results from a large cohort study. JAMA 252: 1023, 1984

 

17

Schuman LM, Coulson AH, Mandel JS et al (eds): Health status of American men— study of post-vasectomy sequelae. J Clin Epidemiol 46: 697, 1993

 

18

Shain RN, Miller WB, Holden AE et al: Impact of tubal sterilization and vasectomy on female marital sexuality: Results of a controlled longitudinal study. Am J Obstet Gynecol 164: 763, 1991

 

19

Miller WB, Shain RN, Pasta DJ: The pre- and poststerilization predictors of poststerilization regret in husbands and wives. J Nerv Ment Dis 179: 602, 1991

 

20

Thapa S: Determinants of fertility in Nepal: Applications of an aggregate model. J Biosoc Sci 19: 351, 1987

 

21

Petitti DB, Klein R, Kipp H et al: A survey of personal habits, symptoms of illness, and histories of disease in men with and without vasectomies. Am J Public Health 72: 476, 1982

 

22

Ball RY, Mitchinson MJ: Obstructive lesions of the genital tract in men. J Reprod Fert 70: 667, 1984

 

23

Smith KD, Chowdhury M, Tcholakian RK: Endocrine effects of vasectomy in humans. In Sciarra JJ, Markland C, Speidel J (eds): Control of Male Fertility, p 169. Hagerstown, MD: Harper & Row, 1975

 

24

Smith G: The effects of ligation of the vasa deferentia and vasectomy on testicular function in the adult rat. J Endocrinol 23: 385, 1962

 

25

Plaut SM: Testicular morphology in rats vasectomized as adults. Science 181: 554, 1973

 

26

Gupta AS, Kothari LK, Bapna RB et al: Surgical sterilization by vasectomy and its effects on the structure and function of the testis in man. Br J Surg 1: 59, 1975

 

27

Bunge RG: Plasma testosterone levels in man before and after vasectomy. Invest Urol 10: 9, 1972

 

28

Wieland RG, Hallberg MC, Zorn EM et al: Pituitary-gonadal function before and after vasectomy. Fertil Steril 23: 779, 1972

 

29

Johnsonbaugh RE, Czerwinski CL, Edson M: Serum hormone levels before and two years after vasectomy. Contraception 16: 563, 1977

 

30

Glavind, K, Lauritsen NR, Klove-Mogensen et al: The effect of vasectomy on the production of the production of plasma lutenizing hormone and follicle stimulating hormone in man. Int Urol Nephrol 22: 553, 1990

 

31

Tyler JPP, Richardson DW, Newton JR: The hormonal and immunological status of vasectomized men. Contraception 19: 599, 1979

 

32

Nikkanen V, Punnonen R: Serum prolactin, FSH, LH and testosterone before and after vasectomy in normal men. Arch Androl 8: 311, 1982

 

33

Kobrinsky NL, Winter JSD, Reyes FI et al: Endocrine effects of vasectomy in man. Fertil Steril 27: 152, 1976

 

34

Fisch H, Laor E, BarChama N et al: Detection of testicular endocrine abnormalities and their correlation with serum antisperm antibodies in men following vasectomy. J Urol 141: 1129, 1989

 

35

Purvis K, Saksena SK, Cekan Z et al: Endocrine effects of vasectomy. Clin Endocrinol 5: 263, 1976

 

36

Naik VK, Thakur AN, Sheth AR et al: The effect of vasectomy on pituitary-gonadal function in men. J Reprod Fertil 48: 441, 1976

 

37

Whitby M, Gordon RD, Seeney N et al: Vasectomy: A long-term study of its effects on testicular endocrine function in man. Andrologia 8: 55, 1976

 

38

de la Torre B, Hedman M, Jensen P et al: Lack of effect of vasectomy on peripheral gonadotrophin and steroid levels. Int J Androl 6: 125, 1983

 

39

Smith KD, Tcholakian RK, Chowdhury M et al: An investigation of plasma hormone levels before and after vasectomy. Fertil Steril 17: 145, 1976

 

40

Rosenberg E, Marks SC, Howard PJ et al: Serum levels of follicle stimulating and luteinizing hormones before and after vasectomy in men. J Urol 111: 626, 1974

 

41

Johnsonbaugh RE, O'Connell K, Engel SB et al: Plasma testosterone, luteinizing hormone, and follicle-stimulating hormone after vasectomy. Fertil Steril 26: 329, 1975

 

42

Goebelsmann V, Bernstein GS, Gale JA et al: Serum gonadotropin, testosterone estradiol and estrone levels prior to and following bilateral vasectomy. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p 165. New York: Academic Press, 1979

 

43

Smith KD, Tcholakian RK, Chowdury M et al: Endocrine studies in vasectomized men. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p. 183. New York: Academic Press, 1979

 

44

Whitby RM, Gordon RD, Blair BR: The endocrine effects of vasectomy: A prospective five-year study. Fertil Steril 31: 518, 1979

 

45

Varma MM, Varma RR, Johanson AI et al: Long-term effects of vasectomy on pituitary-gonadal function in man. J Clin Endocrinol Metab 40: 868, 1975

 

46

Devi PK, Joshi UM, Moodbiri SB et al: Long term effects of vasectomy on pituitary-gonadal axis. Indian J Med Res 66: 591, 1977

 

47

Skegg DCG, Matthews JD, Guillebaud J et al: Hormonal assessment before and after vasectomy. BMJ 1: 621, 1976

 

48

Mo ZN, Huang X, Zhang SC et al: Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels. J Urol 154: 2065, 1995

 

49

Peng XS, Li FD, Miao ZR, et al. Plasma reproductive hormones in normal and vasectomized Chinese males. Int J Androl. 1987. 10(2):471-9

 

50

Hagedoorn JP, Davis JE: Fine structure of the seminiferous tubules after vasectomy in man. Physiologist 17: 236, 1974

 

51

Bigazzi PE, Alexander NJ, Silber SS: Studies on testicular biopsies from vasectomized men. In: Lepow IH, Crozier R (eds): Vasectomy Immunologic and Pathophysiologic Effects in Animals and Man. New York: Academic Press, 1979

 

52

Sun F, Mikhaail-Philips M, Oliver-Bonet M, Ko E, Rademaker A, Turek P, Martin RH. The relationship between meiotic recombination in human spermatocytes and aneuploidy in sperm. Hum Reprod. 2008 Aug;23(8):1691-7.

 

53

Xiang Y1, Luo P, Cao Y, Yang ZW. Long-term effect of vasectomy on spermatogenesis in men: a morphometric study. Asian J Androl. 2013 May;15(3):434-6.

 

54

Jarow JP, Budin RE, Dym M et al: Quantitative pathologic changes in the human testis after vasectomy: A controlled study. N Engl J Med 313: 1252, 1985

 

55

Jarow JP, Goluboff ET, Chang TS et al: Relationship between antisperm antibodies and testicular histologic changes in humans after vasectomy. Urol 43: 521, 1994

 

56

McVicar CM, O'Neill DA, McClure N et al: Effects of vasectomy on spermatogenesis and fertility outcome after testicular sperm extraction combined with ICSI. Hum Reprod. 2005 Oct;20(10):2795-800. Epub 2005 Jun 15.

 PubMed

57

Derrick FC, Glover WL, Kanjuparamban Z et al: Histological changes in the seminiferous tubules after vasectomy. Fertil Steril 25: 649, 1974

 

58

Jenkins IL, Muir VY, Blacklock NJ et al: Consequences of vasectomy: An immunological and histological study related to subsequent fertility. Br J Urol 1979: 51:406

 

59

Mehrotra R, Nath P, Singh KM et al: Changes in seminiferous tubules after vasectomy. Int J Pathol Microbiol 28: 371, 1985

 

60

Flickinger CJ, Howards SS, Herr JC: Effects of vasectomy on the epididymis. Microsc Res Tech 30: 82, 1995

 

61

Appell RA, Evans PR: Vasectomy: Etiology of infectious complications. Fertil Steril 33: 52, 1980

 

62

Barnes MN, Blandy JP, England HR et al: One thousand vasectomies. British Medical Journal 1973; 4: 216.

 

63

Esho JO, Cass AS and Ireland GW: Morbidity associated with vasectomy. J Urol 1973; 110:413.

 

64

Pardanani DS, Patil NG, Pawar HN: Some gross observations of the epididymides following vasectomy: A clinical study. Fertil Steril 27: 267, 1976

 

65

Shapiro EI, Silber SJ: Open-ended vasectomy, sperm granuloma, and postvasectomy orchialgia. Fertil Steril 32: 546, 1979

 

66

Errey BB, Edwards IS: Open-ended vasectomy: An assessment. Fertil Steril 45: 843, 1986

 

67

Jarvis LJ, Dubbins PA: Changes in the epididymis after vasectomy: Sonographic findings. AJR Am J Roentgenol 152: 531, 1989

 

68

McMahon AJ, Buckley J, Taylor A et al: Chronic testicular pain following vasectomy. Br J Urol 69: 188, 1992

 

69

Reddy NM, Gerscovich EO, Jain KA et al: Vasectomy-related changes on sonographic examination of the scrotum. J Clin Ultrasound. 2004 Oct;32(8):394-8.

 PubMed

70

Frates MC, Benson CB, Stober SL. Mobile echogenicities on scrotal sonography: is the finding associated with vasectomy? J Ultrasound Med. 2011 Oct;30(10):1387-90.

 

71

McDonald SW: Vasectomy review: Sequelae in the human epididymis and ductus deferens. Clin Anat 9: 337, 1996

 

72

McDonald SW. Cellular responses to vasectomy. Int Rev Cytol. 2000;199:295-339.

 

73

Légaré C1, Boudreau L, Thimon V, Thabet M, Sullivan R. Vasectomy affects cysteine-rich secretory protein expression along the human epididymis and its association with ejaculated spermatozoa following vasectomy surgical reversal. J Androl. 2010 Nov-Dec;31(6):573-83.

 

74

Légaré C, Thabet M, Picard S, Sullivan R. Effect of vasectomy on P34H messenger ribonucleic acid expression along the human excurrent duct: a reflection on the function of the human epididymis. Biol Reprod. 2001 Feb;64(2):720-7.

 

75

Cornwall GA. New insights into epididymal biology and function. Hum Reprod Update. 2009 Mar-Apr; 15(2): 213–227.

 

76

Sullivan R1, Legare C, Thabet M, Thimon V. Gene expression in the epididymis of normal and vasectomized men: what can we learn about human sperm maturation? J Androl. 2011 Nov-Dec;32(6):686-97.

 

77

Belleannée C1, Légaré C, Calvo E, Thimon V, Sullivan R. microRNA signature is altered in both human epididymis and seminal microvesicles following vasectomy. Hum Reprod. 2013 Jun;28(6):1455-67.

 

78

Thakur AN, Sheth AR, Rao SS et al: Effect of vasectomy on the prostatic function as indicated by seminal maltase activity. Contraception 11: 155, 1975

 

79

Naik VK, Joshi UM, Sheth AR: Long-term effects of vasectomy on prostatic function in men. J Reprod Fertil 58: 289, 1980

 

80

Jackobsen H, Torp-Pedersen S, Juul N et al: The long-term influence of vasectomy on prostate volume and morphology in man. Prostate 13: 57, 1988

 

81

Lassen PM, Thompson IM Jr, Helfrick B: Serum prostate-specific antigen concentration before and after vasectomy. Mil Med 161: 356, 1996

 

82

Zagury D, Bernard J, Leibowitch J et al: HTLV-III in cells cultured from semen of two patients with AIDS. Science 226: 449, 1984

 

83

Anderson DJ, Wolff H, Pudney J et al: Presence of HIV in semen. In Alexander NJ, Gabelnick HL, Spieler JM (eds): Heterosexual Transmission of AIDS, Chap. 14. New York: Alan R. Liss, 1990

 

84

Miller CJ, Shattock RJ. Target cells in vaginal HIV transmission. Microbes Infect. 2003 Jan;5(1):59-67.

 

85

Gupta K1, Klasse PJ. How do viral and host factors modulate the sexual transmission of HIV? Can transmission be blocked? PLoS Med. 2006 Feb;3(2):e79. Epub 2006 Feb 28.

 

86

Lederman MM, Offord RE, Hartley O. Microbicides and other topical strategies to prevent vaginal transmission of HIV. Nat Rev Immunol. 2006 May;6(5):371-82. Review.

 

87

Hladik F, McElrath MJ. Setting the stage: host invasion by HIV. Nat Rev Immunol. 2008 Jun;8(6):447-57

 

88

Ceballos A1, Remes Lenicov F, Sabatté J, Rodríguez Rodrígues C, Cabrini M, Jancic C, Raiden S, Donaldson M, Agustín Pasqualini R Jr, Marin-Briggiler C,Vazquez-Levin M, Capani F, Amigorena S, Geffner J. Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells. J Exp Med. 2009 Nov 23;206(12):2717-33.

 

89

Le Tortorec A, Dejucq-Rainsford N. HIV infection of the male genital tract--consequences for sexual transmission and reproduction. Int J Androl. 2010 Feb;33(1):e98-108

 

90

Anderson DJ, Politch JA, Martinez A et al: White blood cells and HIV-1 in semen from vasectomized seropositive men. Lancet 338: 573, 1991

 

91

Krieger JN, Nirapathpongporn A, Chaiyaporn M et al: Vasectomy and human immunodeficiency virus type 1 in semen. J Urol 159: 820, 1998

 

92

Coombs RW, Reichelderfer PS, Landay AL. Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS. 2003 Mar 7;17(4):455-80.

 

93

Goldacre MJ, Clarke JA, Heasman MA et al: Follow-up of vasectomy using medical record linkage. Am J Epidemiol 108: 176, 1978

 

94

Goldacre M, Vessey M: Record linkage study of morbidity following vasectomy. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, Chap. 27. New York: Academic Press, 1979

 

95

Walker AM, Jick H, Hunter JR et al: Hospitalization rates in vasectomized men. JAMA 245: 2315, 1981

 

96

Petitti DB, Klein R, Kipp H et al: Vasectomy and the incidence of hospitalized illness. J Urol 129: 760, 1983

 

97

Nienhuis H, Goldacre M, Seagroatt V et al: Incidence of disease after vasectomy: A record linkage retrospective cohort study. BMJ 304: 743, 1992

 

98

Goldacre MJ, Wotton CJ, Seagroatt V et al: Immune-related disease before and after vasectomy: an epidemiological databasestudy. Hum Reprod. 2007 May;22(5):1273-8. Epub 2007 Feb 6.

 PubMed

99

Clarkson TB, Lombardi DM, Alexander NJ et al: Diet and vasectomy: Effects on atherogenesis in cynomolgus macaques. Exp Mol Pathol 44: 29, 1986

 

100

Clarkson TB, Alexander NJ, Morgan TM: Atherosclerosis of cynomolgus monkeys hyper- and hyporesponsive to dietary cholesterol: Lack of effect of vasectomy. Arteriosclerosis 8: 488, 1988

 

101

Walker AM, Jick H, Hunter JR et al: Vasectomy and nonfatal myocardial infarction: Continued observation indicates no elevation of risk. J Urol 130: 936, 1983

 

102

Chi I-C, Ko UR, Wilkens LR et al: Vasectomy and nonfatal acute myocardial infarction: A hospital-based case-control study in Seoul, Korea. Int J Epidemiol 19: 32, 1990a

 

103

Giovannucci E, Tosteson TD, Speizer FE et al: A long-term study of mortality in men who have undergone vasectomy. N Engl J Med 326: 1392, 1992

 

104

Goldacre MJ, Wotton CJ, Seagroatt V et al: Cancer and cardiovascular disease after vasectomy: an epidemiological databasestudy. Fertil Steril. 2005 Nov;84(5):1438-43.

 PubMed

105

Guang-hua T, Yu-hui Z, Yue-min M et al: Vasectomy and health: Cardiovascular and other diseases following vasectomy in Sichuan Province, People's Republic of China. Int J Epidemiol 17: 608, 1978

 

106

Goldacre MJ, Holford TR, Vessey MP: Cardiovascular disease and vasectomy: Findings from two epidemiologic studies. N Engl J Med 308: 805, 1983

 

107

Fahrenbach HB, Alexander NJ, Senner JW et al: Effect of vasectomy on the retinal vasculature of men. J Androl 1: 299, 1980

 

108

Walker AM, Jick H, Hunter JR et al: Vasectomy and nonfatal myocardial infarction. Lancet 1: 13, 1981

 

109

Wallace RB, Lee J, Gerber WL et al: Vasectomy and coronary disease in men less than 50 years old; Absence of an association. J Urol 128: 182, 1981

 

110

Linnet L, Moller NPH, Bernth-Petersen P et al: No increase in arteriosclerotic retinopathy or activity in tests for circulating immune complexes 5 years after vasectomy. Fertil Steril 37: 798, 1982

 

111

Rimm AA, Hoffman RG, Anderson AJ et al: The relationship between vasectomy and angiographically determined atherosclerosis in men. Prev Med 12: 262, 1983

 

112

Perrin EB, Woods JS, Namekata T et al: Long-term effect of vasectomy on coronary disease. Am J Public Health 74: 128, 1984

 

113

Rosenberg L, Schwingl PJ, Kaufman DW et al: The risk of myocardial infarction 10 years or more after vasectomy in men under 55 years of age. Am Epidemiol 123: 1049, 1986

 

114

Chi I-C, Kong SK, Wilkens LR et al: Vasectomy and cardiovascular deaths in Korean men: A community-based case-control study. Int J Epidemiol 19: 1113, 1990b

 

115

Roberts HJ: Delayed thrombophlebitis and systemic complications after vasectomy: Possible role of diabetogenic hyperinsulinism. J Am Geriatr Soc 16: 267, 1968

 

116

Roberts HJ: Thrombophlebitis after vasectomy. N Engl J Med 284: 1330, 1971

 

117

Kisker T, Wu K, Culp D et al: Blood coagulation studies in vasectomy. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Man and Animals, p 105. New York: Academic Press, 1979

 

118

Petitti DB, Klein R, Kipp H et al: Physiologic measures in men with and without vasectomies. Fertil Steril 37: 437, 1982

 

119

Alexander NJ, Senner JW, Hoch EJ: Evaluation of blood pressure in vasectomized and non-vasectomized men. Int J Epidemiol 10: 217, 1981

 

120

Mullooly JP, Wiest WM, Alexander NJ et al: Vasectomy, serum assays, and coronary heart disease symptoms and risk factors. J Clin Epidemiol 46: 101, 1993

 

121

Verheught FWA, Tijssen JGP, Boerne GJM et al: Vasectomy and cholesterol. N Engl J Med 305: 462, 1981

 

122

Samuel T, Kolk AHJ, Rumke P et al: Autoimmunity to sperm antigens in vasectomized men. Clin Exp Immunol 21: 65, 1975

 

123

Tung KS: Human sperm antigens and antisperm antibodies: I. Studies on vasectomy patients. Clin Exp Immunol 20: 93, 1975

 

124

Rose NR, Lucas PL: Immunological consequences of vasectomy: Two-year summary of a prospective study. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p 553. New York: Academic Press, 1979

 

125

Anderson DJ, Alexander NJ, Fulgham DL et al: Immunity to tumor-associated antigens in vasectomized men. J Natl Cancer Inst 69: 551, 1982

 

126

Coulson AH, Crozier R, Massey FJ et al: Health status of men—study of post-vasectomy sequelae: Results. J Clin Epidemiol 46: 857, 1993

 

127

Lepow IH, Crozier RH (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man. New York: Academic Press, 1979

 

128

Gubin DA, Dmochowski R, Kutteh WH: Multivariant analysis of men from infertile couples with and without antisperm antibodies. Am J Repro Immunol 39: 157, 1998

 

129

Witkin SS, Zelikovsky G, Bongiovanni AM et al: Sperm-related antigens, antibodies, and circulating immune complexes in sera of recently vasectomized men. J Clin Invest 70: 33, 1982

 

130

Lenzi A, Gandini L, Lombardo F: Antisperm antibody detection: 2. Clinical, biological, and statistical correlation between methods. Am J Reprod Immunol 38: 224, 1997

 

131

Ansbacher R, Hodge P, William A et al: Vas ligation: Humoral sperm antibodies. Int J Fertil 21: 258, 1976

 

132

Linnet L, Hjort T: Sperm agglutinins in seminal plasma and serum after vasectomy: Correlation between immunological and clinical findings. Clin Exp Immunol 30: 413, 1977

 

133

Meinertz H, Linnet L, Wolf H et al: Antisperm antibodies on epididymal spermatozoa. Am J Reprod Immunol 25: 158, 1991

 

134

Rousseaux-Prevost R, de Almeida M, Jouannet P et al: Auto-antibodies to human sperm basic nuclear proteins in infertile and vasectomized men: Characterization of antigens and epitopes recognized by antibodies. Mol Immunol 29: 895, 1992

 

135

Ansbacher R: Humoral sperm antibodies: A 10-year follow-up of vas-ligated men. Fertil Steril 36: 222, 1981

 

136

Hellema HWJ, Rumke PH: Sperm autoantibodies as a consequence of vasectomy: II. Long-term follow-up studies. Clin Exp Immunol 38: 31, 1979

 

137

Weintraub S1, Fahey C, Johnson N, Mesulam MM, Gitelman DR, Weitner BB, Rademaker A. Vasectomy in men with primary progressive aphasia. Cogn Behav Neurol. 2006 Dec;19(4):190-3.

 

138

Han C1, Kim NH, Kwon do Y, Seo WK, Park MH. Lack of association between antisperm antibodies and language dysfunction in Alzheimer's disease. Arch Gerontol Geriatr. 2010 May-Jun;50(3):338-40.

 

139

Köhler TS, Choy JT, Fazili AA, Koenig JF, Brannigan RE. A critical analysis of the reported association between vasectomy and frontotemporal dementia. Asian J Androl. 2012 Nov;14(6):903-4.

 

140

Rumke P, Hellema HWJ: Immunologic studies in long-term follow-up of vasectomized men. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p 521. New York: Academic Press, 1979

 

141

Crewe P, Dawson L, Tidmarsh E et al: Autoimmune implications of vasectomy in man. Clin Exp Immunol 24: 368, 1976

 

142

Howard PJ, James LP: Immunological implications of vasectomy. J Urol 109: 76, 1973

 

143

Bullock JY, Gilmore LL, Wilson JD: Autoantibodies following vasectomy. J Urol 118: 604, 1977

 

144

Matthews JD, Skegg DC, Vessey MP et al: Weak autoantibody reactions to antigens other than sperm after vasectomy. BMJ 2: 1359, 1976

 

145

Hess EV, Herman JH, Hank JL et al: Studies on the immune system in human vasectomy. In Lepow IH, Crozier R (eds): Vasectomy: Immunologic and Pathophysiologic Effects in Animals and Man, p 509. New York: Academic Press, 1979

 

146

Henry JB: Immunological effects of vasectomy. JAMA 225: 642, 1973

 

147

Mumford DM, Gordon HL, Ansbacher R et al: Incidence of lymphocytotoxins in vasectomy patients—a prelminary report. In Sciarra JJ, Markland C, Speidel JJ (eds): Control of Male Fertility, p 196. Hagerstown, MD: Harper & Row, 1975

 

148

White AG, Watson GS, Darg C et al: Lymphocytotoxins in vasectomized men. J Urol 114: 240, 1975

 

149

Jennings PB, Wettlaufer JN, Paulsen CA: Absence of circulating HL-A lymphocytotoxic antibodies in men 21 to 44 months after vasectomy. Fertil Steril 28: 446, 1977

 

150

Bigazzi PW, Kosuda LL, Hser KC et al: Immune complex orchitis in vasectomized rabbits. J Exp Med 143: 382, 1976

 

151

Witkin SS, Brandlund I, Svehag S-E et al: Comparison of different assays for circulating immune complexes in vasectomized and non-vasectomized men. J Clin Lab Immunol 10: 193, 1983

 

152

ICMR Task Force. Long-term effects of vasectomy. Part II: Immunological parameters. An ICMR Task Force study on regulation of male fertility (surgical approaches). Contraception 26:527, 1983

 

153

Alexander NJ, Fulgham DL, Plunkett ER et al: Antisperm antibodies and circulating immune complexes of vasectomized men with and without coronary events. Am J Reprod Immunol Microbiol 12: 38, 1986

 

154

Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008, Cancer incidence and mortality worldwide: IARC CancerBase No. 10. Lyon, France: International Agency for Research on Cancer; 2010.

 

155

Siegel R, Naishadham D, Jemal A. Cancer statistics, CA Cancer J Clin. 2013 Jan;63(1):11-30.

 

156

Platz EA, Giovannucci E. Prostate cancer. In: Schottenfeld D, Fraumeni JF, editors. Cancer epidemiology and prevention.NewYork, NY: Oxford University Press; 2006. p. 1128–50.

 

157

Kheirandish P, Chinegwundoh F. Ethnic differences in prostate cancer. Br J Cancer. 2011 Aug 9;105(4):481-5.

 

158

Ross RK, Paganini-Hill A, Henderson BE: The etiology of prostate cancer: What does the epidemiology suggest? Prostate 4: 333, 1983

 

159

Honda GD, Bernstein L, Ross RK et al: Vasectomy, cigarette smoking, and age at first sexual intercourse as risk factors for prostate cancer in middle-aged men. Br J Cancer 57: 326, 1988

 

160

Mettlin C, Natarajan N, Huben R: Vasectomy and prostate cancer risk. Am J Epidemiol 132; 1056, 1990

 

161

Rosenberg L, Palmer JR, Zauber AG et al: Vasectomy and the risk of prostate cancer. Am J Epidemiol 132; 1051, 1990

 

162

Sidney S, Quesenberry CP, Sadler MC et al: Vasectomy and the risk of prostate cancer in a cohort of multiphasic health-checkup examinees: Second report. Cancer Causes Control 2: 113, 1991

 

163

Spitz MR, Fueger JJ, Babaian RJ et al: Vasectomy and the risk of prostate cancer. Am J Epidemiol 134: 108, 1991

 

164

Giovannucci E, Ascherio A, Rimm EB et al: A prospective cohort study of vasectomy and prostate cancer in US men. JAMA 269: 873, 1993a

 

165

Giovannucci E, Tosteson TD, Speizer FE et al: A retrospective cohort study of vasectomy and prostate cancer in US men. JAMA 269: 878, 1993b

 

166

Hayes RB, Pottern LM, Greenberg R et al: Vasectomy and prostate cancer in US blacks and whites. Am J Epidemiol 137: 263, 1993

 

167

Rosenberg L, Palmer JR, Zauber AG et al: The relation of vasectomy to the risk of cancer. Am J Epidemiol 140: 431, 1994

 

168

Moller H, Knudsen LB, Lynge E: Risk of testicular cancer after vasectomy: Cohort study of over 73,000 men. BMJ 309: 295, 1994

 

169

Hsing AW, Wang RT, Gu FL et al: Vasectomy and prostate cancer risks in China. Cancer Epidemiol Biomarkers Prev 3: 285, 1994

 

170

John EM, Whittemore, AS, Wu AH: Vasectomy and prostate cancer: Results from a multiethnic case-control study. J Natl Cancer Inst 87: 662, 1995

 

171

Zhu K, Stanford JL, Daling JR: Vasectomy and prostate cancer: A case-control study in a health maintenance organization. Am J Epidemiol 144: 717, 1996

 

172

Platz EA, Yeole BB, Cho E et al: Vasectomy and prostate cancer: A case-control study in India. Int J Epidermiol 26: 933, 1997

 

173

Stanford JL, Wicklund KG, McKnight B et al: Vasectomy and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 1999 Oct;8(10):881-6.

 PubMed

174

Lesko SM, Louik C, Vezina R et al: Vasectomy and prostate cancer. J Urol. 1999 Jun;161(6):1848-52; discussion 1852-3.

 PubMed

175

Chacko JA, Zafar MB, McCallum SW et al: Vasectomy and prostate cancer characteristics of patients referred for prostate biopsy. J Urol. 2002 Oct;168(4 Pt 1):1408-11.

 PubMed

176

Cox B, Sneyd MJ, Paul C et al: Vasectomy and risk of prostate cancer. JAMA. 2002 Jun 19;287(23):3110-5.

 PubMed

177

Lynge E: Prostate cancer is not increased in men with vasectomy in Denmark. J Urol. 2002 Aug;168(2):488-90.

 PubMed

178

Rohrmann S, Paltoo DN, Platz EA et al: Association of vasectomy and prostate cancer among men in a Maryland cohort. Cancer Causes Control. 2005 Dec;16(10):1189-94.

 PubMed

179

Holt SK, Salinas CA, Stanford JL. Vasectomy and the risk of prostate cancer. J Urol. 2008 Dec;180(6):2565-7; discussion 2567-8.

 

180

Schwingl PJ, Meirik O, Kapp N, Farley TM; HRP Multicenter Study of Prostate Cancer and Vasectomy. Prostate cancer and vasectomy: a hospital-based case-control study in China, Nepal and the Republic of Korea. Contraception. 2009 May;79(5):363-8.

 

181

Ahmadi H, Allameh F, Baradaran N, Montaser-Kouhsari L, Bazargan-Hejazi S, Salem S, Mehrsai A, Pourmand. GCirculating sex hormones play no role in the association between sexual activity and the risk of prostate cancer. J Sex Med. 2011 Mar;8(3):905-13.

 

182

Guess HA: Invited commentary: Vasectomy and prostate cancer. Am J Epidemiol 132: 1062, 1990

 

183

Sidney S: Vasectomy and the risk of prostatic cancer and benign prostatic hypertrophy. J Urol 138: 795, 1987

 

184

DerSimonian R, Clemens J, Spirtas R et al: Vasectomy and prostate cancer risk: Methodological review of the evidence. J Clin Epidemiol 46: 163, 1993

 

185

Healy B: From the National Institutes of Health: Does vasectomy cause prostate cancer? JAMA 269: 2620, 1993

 

186

Hayes RB: Are dietary fat and vasectomy risk factors for prostate cancer? J Natl Cancer Inst 87: 629, 1995

 

187

Siddiqui MM, Wilson KM, Epstein MM, Rider JR, Martin NE, Stampfer MJ, Giovannucci EL, Mucci LA.Vasectomy and Risk of Aggressive Prostate Cancer: A 24-Year Follow-Up Study. J Clin Oncol. 2014 Jul 7. pii: JCO.2013.54.8446. [Epub ahead of print]

 

188

Bernal-Delgado E, Latour-Perez J, Pradas-Arnal F et al: The association between vasectomy and prostate cancer: A systematic review of the literature. Fertil Steril 70: 191, 1998

 

189

Dennis LK, Dawson DV, Resnick MI: Vasectomy and the risk of prostate cancer: a meta-analysis examining vasectomystatus, age at vasectomy, and time since vasectomy. Prostate Cancer Prostatic Dis. 2002;5(3):193-203.

 PubMed

190

Peterson HB, Howards SS: Vasectomy and prostate cancer: The evidence to date. Fertil Steril 70: 201, 1998

 

191

Borgmeier I, Holman CD: Does vasectomy reversal protect against prostate cancer? Ann Epidemiol. 2004 Nov;14(10):748-9.

 PubMed

192

Cale ARJ, Farouk M, Prescott RJ et al: Does vasectomy accelerate testicular tumour? Importance of testicular examinations before and after vasectomy. BMJ 300: 370, 1990

 

193

Swerdlow AJ, Huttly SR, Smith PG: Testicular cancer and antecedent diseases. Br J Cancer 55: 97, 1987

 

194

Strader CH, Weiss NS, Daling JR: Vasectomy and the incidence of testicular cancer. Am J Epidemiol 128: 56, 1988

 

195

Thornhill JA, Conroy RM, Kelly DG et al: An evaluation of predisposing factors for testis cancer in Ireland. Eur Urol 14: 429, 1988

 

196

Moss AR, Osmond D, Bacchetti P et al: Hormonal risk factors in testicular cancer: A case-control study. Am J Epidemiol 124: 39, 1986

 

197

United Kingdom Testicular Cancer Group: Aetiology of testicular cancer: Association with congenital abnormalities, age at puberty, infertility, and exercise. BMJ 308: 1393, 1994

 

198

Kronmal RA, Krieger JN, Kennedy JW et al: Vasectomy and urolithiasis. Lancet 2: 22, 1988

 

199

Kronmal RA, Krieger JN, Coxon V et al: Vasectomy is associated with an increased risk for urolithiasis. Am J Kidney Dis 29: 207, 1997

 

200

Choe JM, Kirkemo AK: Questionnaire-based outcomes study of nononcological post-vasectomy complications. J Urol 155: 1284, 1996

 

201

Ehn BE, Liljestrand J: A long-term follow-up of 108 vasectomized men. Good counselling routines are important. Scand J Urol Nephrol 29: 477, 1995

 

202

Leslie TA, Illing RO, Cranston DW et al: The incidence of chronic scrotal pain after vasectomy: a prospective audit. BJU Int. 2007 Dec;100(6):1330-3. Epub 2007 Sep 10.

 PubMed

203

Manikandan R, Srirangam SJ, Pearson E et al: Early and late morbidity after vasectomy: a comparison of chronic scrotal pain at1 and 10 years. BJU Int. 2004 Mar;93(4):571-4.

 PubMed

204

Morris C, Mishra K, Kirkman RJ: A study to assess the prevalence of chronic testicular pain in post-vasectomy men J Fam Plann Reprod Health Care. 2002 Jul;28(3):142-4.

 PubMed

205

Myers SA, Mershon CE, Fuchs, EF: Vasectomy reversal for treatment of the post-vasectomy pain syndrome. J Urol 157: 518, 1997

 

206

Temmerman M. Cammu H, Devroey P et al: Evaluation of one-hundred open-ended vasectomies. Contraception 33: 529, 1986

 

207

Schmidt SS: Spermatic granuloma: An often painful lesion. Fertil Steril 31: 178, 1979

 

208

Granitsiotis P, Kirk D: Chronic testicular pain: an overview. Eur Urol. 2004 Apr;45(4):430-6.

 PubMed

209

Christiansen CG, Sandlow JI: Testicular pain following vasectomy: a review of postvasectomy pain syndrome. J Androl. 2003 May-Jun;24(3):293-8.

 PubMed

210

Tandon S, Sabanegh E Jr. Chronic pain after vasectomy: a diagnostic and treatment dilemma. BJU Int. 2008 Jul;102(2):166-9.

 

211

Strebel RT, Leippold T, Luginbuehl T et al: Chronic scrotal pain syndrome: management among urologists in Switzerland. Eur Urol. 2005 Jun;47(6):812-6. Epub 2005 Jan 18.

 PubMed

212

Ahmed I, Rasheed S, White C et al: The incidence of post-vasectomy chronic testicular pain and the role of nerve stripping (denervation) of the spermatic cord in its management. Br J Urol 79: 269, 1997

 

213

West AF1, Leung HY, Powell PH. Epididymectomy is an effective treatment for scrotal pain after vasectomy. BJU Int. 2000 Jun;85(9):1097-9.

 

214

Siu W1, Ohl DA, Schuster TG. Long-term follow-up after epididymectomy for chronic epididymal pain. Urology. 2007 Aug;70(2):333-5

 

215

Sweeney CA, Oades GM, Fraser M, Palmer M. Does surgery have a role in management of chronic intrascrotal pain? Urology. 2008 Jun;71(6):1099-102.

 

216

Hori S, Sengupta A, Shukla CJ, Ingall E, McLoughlin J. Long-term outcome of epididymectomy for the management of chronic epididymal pain. J Urol. 2009 Oct;182(4):1407-12.

 

217

Lee JY, Lee TY, Park HY, Choi HY, Yoo TK, Moon HS, Han JH, Park SY, Lee SW. Efficacy of epididymectomy in treatment of chronic epididymal pain: a comparison of patients with and without a history of vasectomy. Urology. 2011 Jan;77(1):177-82.

 

218

Nangia AK, Myles JL, Thomas AJ JR. Vasectomy reversal for the post-vasectomy pain syndrome: a clinical and histological evaluation. J Urol. 2000 Dec;164(6):1939-42.

 

219

Huang HC, Hsieh ML, Huang ST, Tsui KH, Lai RH, Chang PL. Microsurgical vasectomy reversal: ten-years' experience in a single institute. Chang Gung Med J. 2002 Jul;25(7):453-7.

 

220

Horovitz D1, Tjong V, Domes T, Lo K, Grober ED, Jarvi K. Vasectomy reversal provides long-term pain relief for men with the post-vasectomy pain syndrome. J Urol. 2012 Feb;187(2):613-7.

 

221

Lee JY, Chang JS, Lee SH, Ham WS, Cho HJ, Yoo TK, Lee KS, Kim TH, Moon HS, Choi HY, Lee SW. Efficacy of vasectomy reversal according to patency for the surgical treatment of postvasectomypain syndrome. Int J Impot Res. 2012 Sep;24(5):202-5.

 

222

World Health Organization. Noncommunicable diseases country profiles 2014. July 2014. WHO, Geneva Switzerland.