Safety and Efficacy of Nontherapeutic Male Circumcision: A Systematic Review

In reviewing the posted comments, some clarification on quoted studies seemed appropriate. The 2001 study by Nayir took children with normal ultrasound and laboratory findings and then allocated them to one of three groups: group one were treated with antibiotics before undergoing a circumcision 6 months later-they continued to receive antibiotics as long as cultures were positive; group 2 were circumcised after 3 days of antibiotics; group 3 were controls of uncircumsided children. It would seem the use of antibiotics could be confounding factors for the end-point of this systematic review. The authors were correct to not include this study.

The 1997 study by Taddio et al as published in the Lancet is a cohort study, as defined by the authors. The initial randomization was in use or non-use of Emla for circumcision and this was published in NEJM. This study looked only at pain and was appropriately exluded. The included Lancet study followed these children to determine pain response on future vaccination. Since this cohort study sought to determine if pain during cicumcision correlated with pain at vaccination, one could argue it should have been excluded from this analysis. In reviewing this study, some infants were held by parents during vaccination, while others were not, which seems a confounding factor for pain response.

Competing interests:   None declared

Thank you for inviting me to comment on this article. I had initially planned on responding to content of the article, but since other commentaries have been posted, I will also respond to them.

The authors limited their systematic review to randomized clinical trials (RCTs). The small number of studies that met their criteria reflects the ethical and practical difficulties in performing RCTs of an elective surgical procedure that has no clear medical indication. Some of the commentaries criticize the authors for missing some of the RCTs published after their literature search had been completed in August 2008. One RCT, the study by Nayir et al, may not have been included because of its reliance on bagged urine specimens,[1] which are known to have very high false positive rates in urine specimens obtained from genitally intact children and because it was a study of secondary prevention.[2]

The authors are correct in doubting the applicability of the findings of the RCTs that looked at HIV infection rate in adult men to infants in developed countries.[3-5] There are a number of differences between the men in the study and the average infant in developed countries. The men in the studies were engaging in sexual activity; most infants do not. The men in the studies wanted to be circumcised; most infants do not. The men in the studies gave consent to be circumcised; infants cannot give consent. The men in the studies were well paid to be circumcised, most infants are not paid to be circumcised. The men in the studies had the procedure done with an anesthetic, most infant circumcisions are not. The men in the studies live in countries with a high prevalence of HIV, most infants in developed countries do not.

While RCTs are considered the gold-standard in experimental design, this does not mean that design flaws cannot bias the results. HIV transmission patterns and risk are primarily based on behavior.[6] The HIV-infection RCTs have several serious design flaws that could have influenced behavior. First there is a selection bias, as only men interested in circumcision were included. Second, there is expectation bias, both on the part of the researchers and the participants. It is clear from prior publications that the primary investigators had a desired outcome in mind.[7] Their desire for a particular outcome is, as outlined below, evidenced in the study design. The participants agreed to be in the study because they had been led to believe that circumcision would make them less likely to be infected.[8-16] It is quite possible that they altered their behavior to help the researchers achieve their goal.

Third, there is lead-time bias. Those participants who underwent the procedure were instructed not to have unprotected sex for four to six week following the procedure, while those who were randomized to delaying the procedure for two years were given no such instructions. Lead-time bias is analogous to a ten-mile race in which one team is give a 15-minute head start and expecting the race to be competative. Next, the study was also halted early. This would bias the study results in two ways. First, studies that are halted early are more likely to report inflated treatment effects.[17,18] Second, halting a study early amplifies any lead-time bias. Using the race analogy, not only is one team given a 15-minute head start, midway through the race, the distance of the race is reduced to eight miles.

Next there was an attrition bias. While in the three RCTs 205 men seroconverted during the course of the trial, 958 or more were lost to follow- up.[3-5] With such a low rate of overall seroconversion (1.9%), having this many participants missing in action (8.8%) is a serious problem. One common method of estimating the seriousness of a missing data problem it is to estimated the extreme situations. For example, assume all of missing men from the control group became infected and none of the missing men from the intervention group and calculate the odds ratio. Then make the opposite assumptions. For the three RCTs (References 3, 4, 5, respectively), the first assumption would lead to odds ratios of 0.09, 0.12, and 0.07. The second assumption would lead to odds rations of 2.63, 3.41, and 5.67. This wide of a swing indicates a serious missing data problem.

Finally there is a length bias. Because the trials were planned to be of short duration (24 months) and terminated before completion, it is impossible to know what the long-term outcomes of the trial would be. Also there was no consistent patterns of the timing of seroconversion between the studies.

The RCTs also had other potential flaws. In a randomized trial, randomization should result in an even distribution of demographic factors between the two groups. This did not happen in the trail from South Africa.[3] Also, the number of contacts with members of the two groups should be similar. The men randomized to have immediate circumcision had two to three additional contacts with researchers as part of the procedure and the visits associated with monitoring the recovery process. It is up to the researchers to prove that these additional contacts did not influence or alter participant’s behaviors.

The RCTs were overpowered. Overpowered studies will find a difference that is statistically significant, but perhaps clinically unimportant. While a 50% reduction sounds dramatic, the intervention impacted only a small percentage of the participants (0.67 to 1.25 per 100 patient years).

The numbers of infected men in the three studies (20, 22, and 22 in the three intervention groups and 49, 47, and 45 in the control groups) is strikingly similar, but this could have happen simply by chance.

The studies also made no attempt to determine if the HIV-infections were from heterosexual contacts or nosocomial in origin. Several men who seroconverted in the trial claimed to have had no sexual contacts between their blood tests. It is thought that 20% or more of HIV infections in Africa are from contaminated syringes.[19]

With studies designed with all of the built-in biases supporting an increased treatment effect, one has to question whether a well designed and executed observational study can produce more reliable results than a poorly designed randomized trial.

Other results associated with the three African RCTs have been published since August 2008. Two suggested that those randomized to immediate circumcision were at lower risk for human papillomavirus (HPV) infection.[20,21] As part of the design, both studies sampled only the glans of the penis. Several previously published studies had established that the preferential penile location for HPV differs by circumcision status. For example, HPV is more likely to cultured from the shaft of the circumcised penis and from the glans of the normal penis.[22-26] A study from the University of Washington had shown that if you sample only the glans of the penis of men known to have genital HPV infections, 35% more men with a foreskin will be identified as HPV positive than circumcised men.[22] So it is no great surprise that by sampling only the glans of the penis that both RCTs found that circumcision reduced the risk of HPV infection by 35%. These “dramatic” findings are illusory and can be completely attributed to sampling bias.[27-29]

Two of the RCTs have also reported their experience with genital herpes simple virus type-2 (HSV2) infections. One study failed to find a statistically significant difference.[30] Given that this study was overpowered, is remarkable. The other study reported a significant reduction in genital HSV2 infections in those randomized to immediate circumcision, but made no effort to adjust for lead-time bias.[20] If the 4 to 6 weeks that those randomized to immediate circumcision were essentially out of the race are taken out of the events-per-time denominator and the infections rate comparisons are recalculated, the differences are no longer statistically significantly different.[27]

The RCTs failed to find any difference in the risk of gonorrhea or syphilis.[20] No RCTs have looked at the risk of chancroid infections. While the risk of genital ulcerative disease is lower (which includes syphilis, herpes, and chancroid) in circumcised men,[20,31] the ability to identify the causative agent of genital ulcers in African men in one study was unsuccessful 58% of the time. This study also failed to identify chancroid in any of the 81 men with genital ulcers.[32] Circumcised men, by contrast are at great risk for genital discharge syndrome (which includes gonorrhea, Chlamydia, and non- specific urethritis.)[33]

The reported impact of circumcision on genital infections in their female partners has been a mixed picture.[34,35] Perhaps most disturbing is the clearly unethical trial that found that when an HIV-infected man was randomized to immediate circumcision, this increased the HIV-infection risk of his HIV-negative female partner by 50%.[36] Fortunately, the study was halted before more women were put at risk for infection. Inexplicably, the authors of the study recommended that HIV-positive men continue to be circumcised so these men can avoid stigmatization. This indicates that the authors of the study thought it is more important for an HIV-positive man to “fit in” than it is to reduce the risk HIV-infections in women.

One RCT provided data on men’s sexual satisfaction both before and after undergoing circumcision.[37] They found that men scored sex as being nearly perfect regardless. One possible interpretation of this result is that if a man is looking for the ultimate in sexual satisfaction, he should go to Uganda. On a more practical level, the tool used to measure sexual satisfaction was probably not sensitive enough to document differences. It is analogous to a teacher giving a spelling test where the words are too easy and everyone gets a perfect score. Such a test would not differentiate the strong from the weak spellers. The other possible explanation for the near perfect scores may be that the participants, who were well compensated for their participation, did not want to disappoint their benefactors and answered the surveys accordingly. The same RCT yielded data on the sexual satisfaction of the female partners of men circumcised in the trial.[38] Given the amount the men were paid to participate and the pressure these men could exert on their female partners to satisfy their benefactors, it is difficult to know if their responses were valid. The results of these trials are exactly the opposite of what has been reported in the past.[39-44] Another possible explanation is that the data was collected too soon following the circumcision.

I would like to response to some of the earlier posted comments. First, when accusing someone of cherry-picking, give specific examples. The authors have described their literature search techniques sufficiently that it can be repeated and yield the same results. This is not the case for another recently published “review” that made no attempt to survey the medical literature.[45]

Second, how is it possible that 33% of men can develop illnesses attributable to their foreskin during their lifetime? Let’s do the math. The risk of pathological phimosis, primarily from balanitis xerotica obliterans is less than 2%.[46] The risk of balanitis in a lifetime is 2% to 4%.[47] The risk of penile cancer, which is primarily associated with phimosis (so we may be double counting here) is 0.04%. So the running total is at most 6.04%. Where does the other 26.96% come from? For the circumcised male there is a 1 to 2% risk of immediate bleeding, a 1 to 2% risk of infection (including a 12-fold increased risk of a MRSA infection), a 1% chance of phimosis, a 3 to 5% chance of balanitis (especially in the first three years of life), a 1 to 2% chance of a skin bridge needing surgical separation, a 1 to 2% risk of a circumcision revision, a 5 to 8% chance of needing a meatotomy, a small (but real) risk of death, the small risk of partial or complete amputation of the glans of the penis,[48] and an overall increased risk of developing a sexually transmitted infection.[unpublished meta-analysis] So excluding the STI, major complications, and death risks, the running total is as high as 21%.

Finally, no one is allowed to touch my blanket without my permission.

Footnotes:

1. Nayir A. Circumcision for the prevention of significant bacteriuria in boys. Pediatr Nephrol 2001; 16: 1129-34.

2. Newman CGH, O’Neill P, Parker A. Pyuria in infancy, and the role of suprapubic aspiration of urine in the diagnosis of infections of the urinary tract. Br Med J 1967; 2: 277-9.

3. Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 Trial. PLoS Med 2005; 2(11): e298.

4. Bailey RC, Moses S, Parker CB, Agot K, Krieger JN, Williams CFM, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643-56.

5. Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369: 657-66.

6. Donovan B, Ross MW. Preventing HIV: determinants of sexual behaviour. Lancet 2000; 355: 1897-901.

7. Halperin DT, Bailey RC. Male circumcision and HIV infection: 10 years and counting. Lancet 1999; 354: 1813-5.

8. Bailey RC, Muga R, Poulussen R, Abicht H. The acceptability of male circumcision to reduce HIV infections in Nyanza Province, Kenya. AIDS Care 2002; 14(1): 27-40.

9. Lagarde E, Dirk T, Puren A, Reathe RT, Bertran A. Acceptability of male circumcision as a tool for preventing HIV infection in a highly infected community in South Africa. AIDS 2003; 17: 89-95.

10. Kebaabetswe P, Lockman S, Mogwe S, Mandevu R, Thior I, Essex M, et al. Male circumcision: an acceptable strategy for HIV prevention in Botswana. Sex Transm Infect 2003; 79: 214-9.

11. Rain-Taljaard RC, Lagarde E, Taljaard DJ, Campbell C, MacPhail C, Williams B, et al. Potential for an intervention based on male circumcision in a South African town with high levels of HIV infection. AIDS Care 2003; 15: 315-27.

12. Mattson CL, Muga R, Poulussen R, Onyango T, Bailey RC. Feasibility of medical male circumcision in Nyanza Province, Kenya. East Afr Med J 2004; 81: 230-5.

13. Mattson CL, Bailey RC, Muga R, Poulussen R, Onyango T. Acceptability of male circumcision and predictors of circumcision preference among men and women in Nyanza Province, Kenya. AIDS Care 2005; 17: 182-94.

14. Halperin DT, Fritz K, McFarland W, Woelk G. Acceptability of adult male circumcision for sexually transmitted disease and HIV prevention in Zimbabwe. Sex Transm Dis 2005; 32: 238-9.

15. Scott BE, Weiss HA, Viljoen JI. The acceptability of male circumcision as an HIV intervention among a rural Zulu population, Kwazulu-Natal, South Africa. AIDS Care 2005; 17: 304-13.

16. Lukobo MD, Bailey RC. Acceptability of male circumcision for prevention of HIV infection in Zambia. AIDS Care 2007; 19: 471-7.

17. Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, et al. Randomized trial stopped early for benefit: a systematic review. JAMA 2005; 294: 2203-2209.

18. Mills E, Siegfried N. Cautious optimism for new HIV/AIDS prevention strategies. Lancet 2006; 368: 1236.

19. Gisselquist D. Double standard in research: not protecting participants and their families. Int J STD AIDS 2009; 20: 839-45.

20. Tobian AAR, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, et al. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med 2009; 360: 1298-309.

21. Auvert B, Sobngwi-Tambekou J, Cutler E, Nieuwoudt M, Lissaouba P, Puren A, et al. Effect of male circumcision on the prevalence of human- risk human papillomavirus in young men: results of a randomized controlled trial conducted in Orange Farm, South Africa. J Infect Dis 2009; 199: 14-9.

22. Weaver BA, Feng Q, Holmes KK, Kiviat N, Lee SK, Meyer C, et al. Evaluation of genital sites and sampling techniques for detection of human papillomavirus DNA in men. J Infect Dis 2004; 189: 677-85.

23. Cook LS. Koutsky LA. Holmes KK. Clinical presentation of genital warts among circumcised and uncircumcised heterosexual men attending an urban STD clinic. Genitourin Med 1993; 69: 262-4.

24. Aynaud O, Piron D, Bijaoui G, Casanova JM. Developmental factors of urethral human papillomavirus lesions: correlation with circumcision. BJU Int 1999; 84: 57-60.

25. Hernandez BY, Wilkens LR, Zhu X, McDuffie K, Thompson P, Shvetsov YB, et al. Circumcision and human papillomavirus infection in men: a site- specific comparison. J Infect Dis 2008; 197: 787-94.

26. Nielson CM, Schiaffino MK, Dunne EF, Salemi JL, Giuliano AR. Associations between male anogenital human papillomavirus infection and circumcision by anatomic site sampled and lifetime number of female sex partners. J Infect Dis 2009; 199: 7-13.

27. Storms MR. Male circumcision for the prevention of HSV-2 and HPV infections. N Engl J Med 2009; 361: 307.

28. Van Howe RS. Sampling bias explains association between human papillomavirus and circumcision. J Inf Dis 2009; 200: 832.

29. Van Howe RS, Storms MR. Circumcision to prevent HPV infection. Lancet Oncol 2009; 10: 746-7.

30. Sobngwi-Tambekou J, Taljaard D, Lissouba P, Zarca K, Puren A, Legarde E, et al. Effect of HSV-2 serostatus on acquisition of HIV by young men: results of a longitudinal study in Orange Farm, South Africa. J Infect Dis 2009; 199: 958-64.

31. Auvert B, Bailey R, Gray R. Results of the South African trial, the Kenyan trial, and the Rakai Trial. Centers for Disease Control and Prevention Consultation on Public Health Issues Regarding Male Circumcision in the United States for the Prevention of HIV Infection and Other Health Consequences. Atlanta, Georgia. April 26, 2007.

32. Gray RH, Serwadda D, Tobian AA, Chen MZ, Makumbi F, Suntoke T, Kigozi G, Nalugoda F, Iga B, Quinn TC, Moulton LH, Laeyendecker O, Reynolds SJ, Kong X, Wawer MJ. Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: Analyses from the Rakai trials. PLoS Med 2009; 6(11): e1000187.

33. Van Howe RS. Genital ulcer disease and sexually transmitted urethritis and circumcision: a meta-analysis. Int J STD AIDS 2007; 18: 799-809.

34. Turner AN, Morrison CS, Padian NS, Kaufman JS, Salata RA, Chipato T, Mmiro FA, Mugerwa RD, Behets FM, Miller WC. Men's circumcision status and women's risk of HIV acquisition in Zimbabwe and Uganda. AIDS 2007; 21: 1779-89.

35. Gray RH, Kigozi G, Serwadda D, Makumbi F, Nalugoda F, Watya S, Moulton L, Chen MZ, Sewankambo NK, Kiwanuka N, Sempijja V, Lutalo T, Kagayii J, Wabwire-Mangen F, Ridzon R, Bacon M., Wawer MJ. The effects of male circumcision on female partners’ genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. Am J Obstetr Gynecol 2009; 200: e1-7.

36. Wawer MJ, Makumbi K, Kigozi G, Serwadda D, Watya S, Nalugoda F, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 2009; 374: 229-237.

37. Kigozi G, Watya S, Polis CB, Buwenbo D, Kiggundu V, Wawer MJ, et al. The effect of male circumcision on sexual satisfaction and function, results from a randomized trial of male circumcision for human immunodeficiency virus prevention, Rakai, Uganda. BJU Int 2008; 101: 65-70.

38. Kigozi G, Lukabwe I, Kagaayi J, Wawer MJ, Nantume B, Kigozi G, et al. Sexual satisfaction of women partners of circumcised men in a randomized trial of male circumcision in Rakai, Uganda. BJU Int 2009; 104: 1698-701.

39. O’Hara K, O’Hara J. The effect of male circumcision on the sexual enjoyment of the female partner. BJU Int 1999; 83 (suppl 1): 79-84.

40. Fink KS, Carson CC, DeVellis RF. Adult circumcision outcomes study: effect on erectile function, penile sensitivity, sexual activity and satisfaction. J Urol 2002; 167: 2113-6.

41. Coursey JW, Morey AF, Summerton DJ, Secrest C, White P, al. Erectile function after anterior urethroplasty. J Urol 2001; 166: 2273-6.

42. Collins S, Upshaw J, Rutchik S, Ohannessian C, Ortenberg J, Albertsen P. Effects of circumcision on male sexual function: debunking a myth? J Urol 2002; 167: 2111-2.

43. Shen Z, Chen S, Zhu C, Wan Q, Chen Z. [Erectile function evaluation after adult circumcision] Zhonghua Nan Ke Xue 2004; 10: 18-9.

44. Kim DS, Pang M-G. The effect of male circumcision on sexuality. BJU Int 2007; 99: 619-622.

45. Tobian AAR, Gray RH, Quinn TC. Male circumcision for the prevention of acquisition and transmission of sexually transmitted infections: the case for neonatal circumcision. Arch Pediatr Adolesc Med 2010; 164: 78-84.

46. Shankar KR, Rickwood AMK. The incidence of phimosis in boys. BJU Int 1999; 84: 101-2.

47. Escala JM, Rickwood AM. Balanitis. Br J Urol 1989; 63: 196-7.

48. Van Howe RS. A cost-utility analysis of neonatal circumcision. Med Decis Making 2004; 24: 584-601.

Competing interests:   None declared

I would like to add the function of foreskin/prepuce and also the the options for circumcision decision. --------------------------------- Foreskin Functions (new)

What is the function of foreskin? The World Health Organization (WHO) states that there is "debate about the role of the foreskin, with possible functions including keeping the glans moist, protecting the developing penis in utero, or to enhance sexual pleasure due to the presence of nerve receptors". (http://whqlibdoc.who.int/publications/2007/9789241596169_eng.pdf - page 18)

I would like to suggest an additional function of “foreskin” : Foreskin is a warm-waterproof blanket for the glans/penis-head

A Blanket What are the functions of a blanket? 1. To protect your body when the weather or environment is cold or hot (keep you warm). 2. To protect your body from mosquito or any insects bite.

Do you need to say thank you when someone give you a blanket? Yes, you need to, because a blanket can protect you from cold weather and insects. No, you don’t have to, you can reject it when the blanket can’t be used for keeping you warm or keep you away from insects, or it is an unusual blanket.

Do you need to clean your blanket? Yes, you have to clean it regularly, however when you were a kid your parent might help you washing it. If you don’t wash it, it can be dirty, stink and become a source of diseases.

Do you need a beautiful blanket? It is great if you are given a beautiful blanket; however a standard blanket should be good enough as long as it can make you warm and keep you away from insects.

Are you at risk if you allow unknown people using your blanket? Yes, other people can transmit their disease to you such as flu, skin diseases, etc. It is better for you to reject your blanket which was used by unknown people.

Summary: A blanket can be useful for you and can be a source of disease if you do not keep it clean. Without a blanket especially in cold environment, you will suffer more than others who still have blanket.

Your decision to keep or reject a blanket depends on: 1. whether you get a standard and useful blanket or not 2. whether you have commitment to clean it regularly or not 3. whether you want to prevent it being used by unknown people or not

The Foreskin

What are the functions of the foreskin? 1. To protect glans/penis-head (indirectly protect prostate) when the weather or environment is cold or hot (keep your glans and prostate warm) 2. To protect your glans from mosquito or any insects bite

Do you need to say thank you when God give you foreskin? Yes, you need to; because the foreskin can protect you from cold environment and insects. No, you don’t have to; you can reject (circumcise) it when the foreskin can’t be used for keeping you warm or you get an abnormal foreskin.

Do you need to clean your foreskin? Yes, you have to clean it regularly, however when you were a kid, your parent might help you clean it. If you don’t clean it, it can be dirty, stink and become a source of diseases.

Do you need a beautiful foreskin? It is great if you are given a beautiful foreskin; however a standard and normal foreskin should be good enough as long as it can make your glans warm.

Are you at risk if you allow unknown people using your foreskin (free sex habit)? Yes, if you have free sex habit or changing sex partner habit, you are at risk, you can be infected by diseases such as AIDS, Herpes, or other male genital disease. It is better for you not to use that foreskin again (circumcise it)

Summary: The foreskin can be useful for you and can be a source of disease if you do not keep it clean. Without foreskin especially in cold environment, you will suffer more than others who still have foreskin.

Your decision to circumcise (reject) or uncircumcised (keep) the foreskin depends on: 1. whether you get a standard/normal foreskin or not 2. whether you have commitment to clean it regularly or not 3. whether you want to prevent it from being used by unknown people or not (whether you want to avoid free sex or changing partner habit or not).

If all of your answers are “Yes”, then circumcision is not compulsory If one of your answers is “No” then circumcision is compulsory

Based on the explanations, we can understand the conclusion by many researchers to choose circumcision (reject the “blanket”) option to prevent HIV virus or other male genital diseases in several countries which habit of changing sex partner is the main caused of disease spreading.

Hope this can be an additional conclusion that circumcision can not be applied worldwide and can not be applied to all new born babies.

I also make an hypothesis about the effect of circumcision to prostate problems in my blog:

http://healthsecrets-rich.blogspot.com/

------------------ Thanks, Rich

Competing interests:   None declared

The foreskin is at least half of the skin of the normal penis. The complication rate of circumcision is 100% because in every case the ridged bands are either removed, or in relatively few cases, exposed to desiccation. The ridged bands contain thousands of the most sensitive nerve endings in the entire penis.

Regretfully, it is necessary to state that a person who circumcises is violating the Golden Rule; First, do no harm; is torturing his or her patient, by definition (look it up); is mutilating his patient, again by definition; is committing fraud; is violating 8 of the 9 Principles of Ethics of the AMA Code of Ethics; is violating the Nuremberg Code of Ethics. If these facts are not enough to stop someone from removing normal body parts from another person without their permission, I do not know what will.

Competing interests:   None declared

This review claims there is no randomized controlled trial (RCT) evidence for circumcision in prevention of urinary tract infections (UTI), not mentioning the very strong, consistent evidence from observational studies of a 10-fold protective effect. But THERE IS RCT evidence as well!! Nayir reported in Pediatr Nephrol in 2001 (vol 16, pp1129-34) the results of a RCT on UTIs in boys with UTI and found that circumcision reduced recurrence by 96% or more.

A thorough evaluation of the literature and simple calculations by J.H. Waskett (unpublished) have revealed that UTIs affect 1 in 3 uncircumcised males over their lifetime, but only 1 in 20 circumcised males, so by referring only to the rate in the first year of life, as Perera et al. do, obfuscates rather than informs.

Perera et al. say that “no other sexually transmitted infections were reported upon [sic!] in the RCT literature. This is also not true. There is a large body of RCT data that shows that circumcision prevents oncogenic human papillomavirus (that causes penile cancer and cervical cancer), herpes simplex type 2, Trachomonis vaginalis, syphilis and chancroid.

Their article refers to “apocrine glands in the inner prepuce [that] secrete a lysozyme that reportedly kills HIV-1 in vitro”, but cite a secondary reference, failing to check the original source, which is by Paul Fleiss, a notorious anti-circumcision activist and convicted felon, found guilty of money laundering for hiding the proceeds of his daughter Heidi’s escort services from the Internal Revenue Service in the USA. One might think that if there was a more credible source for Perera's claim then that is what should appear in a professional journal, not dubious anti-circumcision sources.

The tone of the review and the manner in which statements are made cause it to appear biased against circumcision. This detracts from the credibility one might expect in the medical literature, where impassioned, balanced communication is expected.

The authors say they retrieved approx. 1,200 references, yet based their review on only a few of these, thus omitting a huge body of quality scientific findings attesting to the benefits of circumcision. I would encourage the reader to read my very much more complete and up-to-date, evidence-based appraisal of circumcision that cites over 1,000 references. This can be found at http://www.circinfo.net.

Professor Brian J. Morris

Competing interests:   None declared

Thank you for inviting me to comment. I would like to alert readers to the fact that a detailed Cochrane review on the effectiveness of male circumcision for preventing HIV acquisition in heterosexual men was published in early 2009, prior to publication of this article. The full citation is:

Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD003362. DOI: 10.1002/14651858.CD003362.pub2.

The authors only refer to a previous Cochrane review of observational studies published in 2003 (reference #29) and not to the more recent review of RCTs. A small point is that the authors refer to a statement in the review regarding lysozyme which should be more correctly referenced as a citation in our review, rather than the review itself.

Competing interests:   I am the lead author on a Cochrane review evaluating the effectiveness of male circumcision for preventing the heterosexual transmission of HIV in men