Cardiovascular disease

The initial reports of an association between vasectomy and cardiovascular disease were made in studies conducted by Clarkson and Alexander. These authors observed that two different species of vasectomized monkeys ( Macaca fascicularis and Macaca mulatta ) had more extensive atherosclerosis compared with age-matched controls, and they speculated that this difference was the result of circulating antisperm antibody immune complexes that exacerbated atherosclerosis. Follow-up studies, including one by the original authors, Clarkson and Alexander, failed to substantiate the initial reported association between vasectomy and atherosclerosis. Campbell and colleagues investigated the possible link between vasectomy and cardiovascular disease in humans by assessing the distensibility of posterior tibial arteries using Doppler ultrasonographic techniques. The authors reported that men who had undergone prior vasectomy had reduced posterior tibial artery distensibility compared with controls, and they concluded that vasectomized men may be at risk for accelerated development of peripheral arterial disease.

Numerous subsequent studies in humans have dispelled an association between vasectomy and cardiovascular disease. These studies collectively assessed a large array of specific cardiovascular parameters, including blood pressure, angiographically determined atherosclerosis, coronary heart disease, myocardial infarction, and death from cardiovascular disease. In sum, these studies concluded that patients who had undergone vasectomy were not at increased cardiovascular risk compared with controls. Even in patients who are 20 or more years postvasectomy, no increase in atherosclerosis or coronary heart disease has been observed. Finally, Kisker and colleagues assessed parameters that could predispose patients to thrombotic events, including blood coagulation factors, thrombin monomer, and circulating platelet aggregate ratios. The authors found no differences in these markers of thrombotic disease when comparing men who had undergone vasectomy with controls.

Other postulated circulating immune complex disorders

Two small studies in rabbits and macaques reported an association between vasectomy and glomerulonephritis, and the authors postulated that circulating immune complex deposition was the mediating factor. Several subsequent investigations failed to show any changes in renal function suggestive of glomerulonephritis or any increased prevalence of glomerulonephritis among vasectomized men when compared with nonvasectomized men. Repeated studies have also failed to substantiate the initial concerns of circulating immune complex formation induced by postvasectomy antisperm antibodies, because circulating immune complexes were not found to be persistently elevated in men who underwent vasectomy when compared with controls. A recent study with a mean follow-up of 13 years similarly demonstrated that men who underwent vasectomy had no long-term increased risk for several other immune system–related diseases, such as ankylosing spondylitis, asthma, diabetes, inflammatory bowel disease, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or thyrotoxicosis. The significance of antisperm antibodies in vasectomized men is still unclear, but they have not been definitively associated with any pathologic processes aside from the desired result of male sterility.

Other postulated circulating immune complex disorders

Two small studies in rabbits and macaques reported an association between vasectomy and glomerulonephritis, and the authors postulated that circulating immune complex deposition was the mediating factor. Several subsequent investigations failed to show any changes in renal function suggestive of glomerulonephritis or any increased prevalence of glomerulonephritis among vasectomized men when compared with nonvasectomized men. Repeated studies have also failed to substantiate the initial concerns of circulating immune complex formation induced by postvasectomy antisperm antibodies, because circulating immune complexes were not found to be persistently elevated in men who underwent vasectomy when compared with controls. A recent study with a mean follow-up of 13 years similarly demonstrated that men who underwent vasectomy had no long-term increased risk for several other immune system–related diseases, such as ankylosing spondylitis, asthma, diabetes, inflammatory bowel disease, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or thyrotoxicosis. The significance of antisperm antibodies in vasectomized men is still unclear, but they have not been definitively associated with any pathologic processes aside from the desired result of male sterility.

Testicular cancer

Observations regarding a possible association between vasectomy and testicular cancer were first reported in a 1988 case-control study by Strader and colleagues conducted in western Washington state. On closer analysis, however, the association between vasectomy and testicular cancer in this study was noted to be present only in Catholic men and was speculated to be caused by bias in underreporting a history of vasectomy by Catholic controls. The possibility of an association between vasectomy and testicular cancer re-emerged when Thornhill and colleagues, from Ireland and Cale and colleagues from Scotland reported that the risk of testicular cancer may be elevated after vasectomy. Both studies were small, with the first reporting on three patients and the second reporting on eight patients diagnosed with testicular cancer shortly after vasectomy. The authors of each of these studies suggested that vasectomy may accelerate the growth of an existing tumor, whereas Jorgensen and colleagues in a subsequent manuscript hypothesized that vasectomy may facilitate the development of testicular cancer from previously present carcinoma in situ, a preinvasive lesion. In 1994, Moller and colleagues attempted to clarify the relationship between vasectomy and testicular cancer using computerized linkage of four population-based registers in Denmark. The authors compared cancer rates among the cohort of men who had undergone vasectomy with the whole Danish population. The authors found no increase in testicular cancer in the cohort of 73,917 vasectomized men. They concluded that vasectomy is neither likely to induce testicular tumorigenesis, nor to accelerate the growth and diagnosis of noninvasive precursor lesions or clinically unrecognized tumors. In 1994, the United Kingdom Testicular Cancer Study Group published a population-based case-control study on the etiology of testicular cancer involving 794 men from nine health regions in England and Wales. The authors found no association between vasectomy and testicular cancer. These final two studies are the largest to date, and both effectively dispel the notion that vasectomy is associated with testicular cancer.

Prostate cancer

In 1990, two separate case-control studies by Rosenberg and colleagues and Mettlin and colleagues generated significant debate by reporting an association between vasectomy and prostate cancer. These two studies supported the finding of an association between vasectomy and prostate cancer that was initially reported by Honda and colleagues in 1988. Critics were quick to note, however, that the control group in the study by Rosenberg and colleagues had a vasectomy rate far below the general population. They contended that the apparent bias in the control group exaggerated potential differences between cases and controls. A follow-up study by the original authors with better accounting for this bias revealed no association between vasectomy and prostate cancer. Despite this follow-up report, numerous subsequent studies by other groups also suggested an association between vasectomy and prostate cancer ( Table 1 ). These studies have been criticized as suffering from some degree of detection bias or surveillance bias, because men who have undergone vasectomy typically have access to a urologist and are more likely to be screened for prostate cancer. Other studies associating vasectomy and prostate cancer have been plagued by similar problems of selection bias stemming from an overall differential access to health care between cases and controls. This is a reflection of the fact that vasectomies in the United States are generally performed on men of higher socioeconomic backgrounds who have good access to health care and frequently use health care resources.

The issue of possible confounding has also been noted in studies reporting links between vasectomy and prostate cancer. This was illustrated in 1993 when two separate cohort studies from Giovannucci and colleagues in the Journal of the American Medical Association demonstrated an association between vasectomy and prostate cancer. According to these studies, the age-adjusted relative risk for prostate cancer among men with vasectomies was 1.66 (95% confidence interval [CI], 1.25–2.21) and 1.56 (95% CI, 1.03–2.37). In an editorial within the same issue of the Journal of the American Medical Association , Howards and Peterson wrote that the most likely noncausal explanation for Giovannucci and colleagues findings was unmeasured confounding, based on the fact that the specific etiology of prostate cancer remains unknown. In 1996, Sandlow and Kreder surveyed 1500 urologists regarding the impact of reports of an association between vasectomy and prostate cancer on urologists’ practice patterns. Although 90% of the 759 respondents noted that these reports had little or no effect on their practice of vasectomy, 27% acknowledged that they screened vasectomized men earlier from prostate cancer. Additionally, 20% responded that they are reluctant to recommend a vasectomy to a man with a strong family history of prostate cancer. The authors concluded that over one fourth of the urologists who screen for prostate cancer altered their screening patterns, despite responding that the studies had not affected their practice patterns.

In the years that followed, multiple studies failed to find an association between vasectomy and prostate cancer (see Table 1 ). Of these, perhaps the most notable was a large population-based, case-control study from New Zealand that was published in 1992 and compared 923 prostate cancer patients with 1224 matched controls. Although a case-control design, this study benefited from its large population sample. New Zealand has the highest vasectomy prevalence in the world, and statutory identification of cancer into a national registry, providing the framework to avoid many potential sources of confounding. This study found no significantly increased risk of prostate cancer in men with prior vasectomies (RR of 0.92; 95% CI, 0.75–1.14), even after adjusting for patient age, age at vasectomy, time since vasectomy, age of prostate cancer diagnosis, family history of prostate cancer, and stage of cancer. A case-control study specifically designed to address the issue of risk of prostate cancer in specific subgroups was published in 2002. This study assessed 1001 men and revealed no association between prostate cancer and age at vasectomy, years elapsed since vasectomy, family history of prostate cancer, or race. This publication supported the assertion that vasectomy does not lead to an increased risk of prostate cancer, even in men with longer follow-up and in populations at increased risk for this disease, such as African American men or men with a family history of prostate cancer.