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Prostate news article, August 2007


LIFESTYLE AND THE UROLOGIST

 

Article by:   Professor Roger Kirby, Chairman, Prostate UK and Dr Michael Kirby

 Roger Kirby

“Lifestyle” is currently a buzz word, but unfortunately those clinicians who predominantly deal with prostate-related illnesses seldom pay sufficient attention to this important aspect of their patients’ problems. However, evidence is steadily accumulating that lifestyle and diet are extremely important components in both the causes of and remedies for both prostate-related disorders and sexual dysfunction.

More and more men nowadays are either overweight or obese(1) and the typical “pot belly”  that they exhibit is strongly linked with both the metabolic syndrome and diabetes mellitus (Figure 1). Cholesterol levels in males are also often too high carrying increased risks of cardiovascular disease and premature death. Obesity has recently been proposed as a risk factor for prostate cancer in a paper by Ribeiro et al(2), and it also undoubtedly increases the risks of complications during and after surgical intervention for the disease, whether open or laparoscopic.

An increased waist circumference and/or body mass index (BMI) is significantly associated with increased cardiovascular risk as well as all the other deleterious components of the metabolic syndrome, including diabetes mellitus. Exhortation by clinicians to adopt a more sensible diet and to increase the amount of regular exercise is therefore in order. The beneficial effect of a high intake of fruit and vegetables has been reinforced by a recently published meta-analysis(3). If urologists feel uneasy with this unaccustomed role they might be encouraged by the recent smaller study by Giovannucci et al(4) which demonstrated that men who undertook more than 3 hrs of vigorous exercise per week reduced their risk of developing advanced prostate cancer or dying from the disease by around 70%. If this approach seems too daunting to the urological patient, he may sometimes be brought on side by the counter proposal that regular alcohol intake in men appears to offer some protection against coronary artery disease(5).

Erectile dysfunction has been shown to lead to decreased quality of life in men(6). Moreover, there is convincing epidemiological evidence that links the subsequent risk of erectile dysfunction to the presence of risk factors for cardiovascular disease, which include increased body weight, hypertension, diabetes and dyslipidaemia(7). It is endothelial dysfunction that links ED to heart disease, and potency problems should therefore prompt investigation for cardiovascular disease in asymptomatic men(8). The metabolic syndrome is characterised by abnormal endothelial function and there is a clear incremental increase in the prevalence of ED that is associated with a linear impairment of endothelial function score as the number of components of the metabolic syndrome increase(9). It has been shown that lifestyle changes, which include detailed advice about how to achieve a reduction in total body weight of 10% or more and individual guidance on increasing their level of physical activity over a 2 year period, led to an improvement in sexual function in about one-third of obese men with erectile dysfunction at baseline(10).

It has been known for years that exercise and weight reduction alone will yield beneficial effects on lipid profiles and weight(11). However, if total and LDL cholesterol are significantly elevated there is now abundant evidence that lowering these with a statin will result in a significant reduction in cardiovascular risk. Statins possess a variety of pleiotropic effects with vasculoprotective and cardioprotective activity, which may be attributable, at least in part, to inhibition of vascular smooth muscle cell proliferation and the way they accelerate reendotheliasation(12). Their beneficial effects on endothelial cells as well as on endothelial cell function, appears to be related to improved nitric oxide bioavailability. Statins induce endothelial nitric oxide synthase mRNA stability in endothelial cells and promote endothelial nitric oxide synthase activity through a P13K/Akt dependent pathway, which is the common signal transduction pathway shared by growth factors such as vascular endothelial growth factors or fibroblast growth factors (FGFs). Statins may influence reendothelialisation by their effects on mobilising, differentiating and improving the survival of endothelial progenitor cells(13). It has been proposed that these mechanisms might all contribute to the improved nitric oxide (NO) bioavailability(14). A recent meta-analysis revealed that a 1 mmol/L reduction in LDL cholesterol translated into an 18% reduction of heart attack or stroke(15). Intriguingly, there is also emerging evidence that statins may not only reduce PSA levels but also offer some chemopreventative protection against prostate cancer(16). In addition one might expect statins to be beneficial in ED; preliminary data on the beneficial effect of statins on ED has been reported(17-20).

These evidence-based observations lead to the conclusion that the urologist of the future should develop a broader, more holistic view of his or her role as a specialist in Men’s Health(21). Instead of focusing exclusively on the prostatic or sexual dysfunction, attention should be paid to other concomitant medical issues, especially dyslipidaemia, but also diabetes and hypertension, many of which may in fact pose a greater threat to quality of life and longevity than the urological problem itself(22). Most of these conditions can be easily ameliorated with some focused lifestyle advice and the judicious introduction of medical therapy including a statin. This medical approach in our view provides the way ahead for our specialty for the future.

References:

  1. Vasan RS, Pencina MJ, Cobain M et al.  Estimated risks for developing obesity in the Framingham Heart Study. Ann Intern Med 2005 143: 473-480.
  2. Ribeiro R, Lopes C, Medeiros R The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives. Prostate Cancer and Prostatic Diseases 2006; 9:19-24.
  3. He FJ, Nawson CA, MacGregor GA. Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet 2006; 367: 320-226.
  4. Giovannucci EL, Liu Y, Leitzmann MJ et al A prospective study of physical activity and incident and fatal prostate cancer. Arch Int Med 2005,165:1005-10.
  5. Tolstrup J, Jensen MK, Tjonneland et al. Prospective study of alcohol drinking patterns and coronary heart disease in women and men. BMJ 2006;322:1244-7
  6. Litwin MS, Nied RJ, Dhanani N. Health related quality of life in men with erectile dysfunction. J Gen Intern Med 1998; 13: 159-166. 
  7. Fung MM, Bettencourt R, Barrett-Connor H. Heart disease risk factors predict erectile dysfunction 25 years later. J Am Col Cardiol 2004; 43: 1405-1411.
  8. Blumentals WA, Gomez-Caminero A, Joo S et al. Should erectile dysfunction be considered as a marker for acute myocardial infarction? Int J Clin Impot Res 2004; 16: 350-353.
  9. Eposito K, Giugliano F, Martedi E et al. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005, 28; 5: 1201-1203.
  10. Esposito K, Giugliano F, Di Palo C et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomised controlled trial. JAMA 2004, 291; 24: 2978-2984.)
  11. Vu Tran Z, Weltman A.  Differential effects of exercise on serum lipid and lipoprotein levels seen with changes in body weight: a meta-analysis.  JAMA 1985;254:919-24
  12. Corsini A, Pazzucconi F, Pfister P et al. Inhibitor of proliferation of arterial smooth muscle cells by fluvastatin. Lancet 1996; 348: 1584.
  13. Walter DH, Rittig K, Ferdinand H et al. Statin therapy accelerates reendothelialisation. Circulation 2002; 105: 3017-3024.
  14. Walter DH, Dimmeler S, Zeiher AM. Effects of statins on endothelium and endothelial progenitor cell recruitment. Semin Vasc Med 2004, 4; 4: 385-93.
  15. Cholesterol Treatment Trialists Collaborators.  Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90056 participants in 14 randomized trials of statins.  The Lancet 2005; 366:12671278.
  16. Shannon J, Tewoderos S Garzotto M et al Statins and prostate cancer risk: a case control study. Am J Epidemiol 2005, 162:318-25.
  17. Saltzman EA, Guay AT, Jacobson J.  Improvement in erectile dysfunction in men with organic erectile dysfunction by correlation of elevated cholesterol levels: a clinical observation.  J Urol 2004; 172:255-258.
  18. Goldstraw M, Kirby RS, Amoroso P Do statins protect against prostate cancer? BJI Int 2006 97:1147
  19. Herrman HC, Levine LA, Macaluso J Jr, Walsh M, Bradbury D, Schwartz S, Mohler ER III, Kimmel SE.  Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil?  Hypothesis and Pilot Trial Results.  J Sex Med 2006; 3: 303-308.
  20. Cyrus-David M, Weinberg A, Thompson T, Kadmon D. The effect of statins on serum prostate specific antigen levels in a cohort of airline pilots: a preliminary report. J Urol 2005; 173:1923-1925.
  21. Kirby RS, The urologist as an advocate of men’s health. BJU Int 2005; 95:929.
  22. Kirby RS, Kirby MG, Amoroso P, Dean J and Gould D, Steps by which better overall health for men could be achieved. BJU Int 2006 98:285-8.

Fig 1. Features of the metabolic syndrome.

Lifestyle risks

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