- Email: [email protected]
Effects of Obesity and Weight Loss in Patients With Nononcological Urological Disease
Review Article
Effects of Obesity and Weight Loss in Patients With Nononcological Urological Disease Vivek Natarajan,*,† Viraj Master† and Kenneth Ogan‡ From the Department of Urology, Emory University School of Medicine, Atlanta, Georgia
Abbreviations and Acronyms BMI ⫽ body mass index BPH ⫽ benign prostatic hyperplasia ED ⫽ erectile dysfunction Submitted for publication August 29, 2008. * Correspondence: The Emory Clinic, Department of Urology, 1365 Clifton Rd., Suite B, Atlanta, Georgia 30322 (telephone: 404-778-3038; FAX: 404-778-4006; e-mail [email protected]). † Nothing to disclose. ‡ Financial interest and/or other relationship with Cook Urological.
Editor’s Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 2834 and 2835.
Purpose: We reviewed the effects of obesity and long-term weight loss on nononcological urological disease, particularly urinary stone formation, erectile dysfunction, female sexual dysfunction, voiding dysfunction and urinary incontinence. Materials and Methods: A literature search was conducted using Ovid’s MEDLINE®, accessed through Emory University’s Health Sciences Library web site. The subject headings obesity, weight loss surgery, urolithiasis, sexual dysfunction, erectile dysfunction, benign prostatic hyperplasia and urinary incontinence were used as indices for the search. Articles published earlier than 10 years before the literature review (performed in summer of 2007) were not used. Results: There is ample evidence to support an increased risk of urolithiasis in obese patients. However, the effects of long-term weight loss on urinary stone formation have not been studied as extensively in the literature. It is unclear whether the decreased food intake after surgical weight loss procedures may negate the associated risk of malabsorption and decrease the risk of urolithiasis in the long term. The incidence and severity of erectile dysfunction in men increase with obesity. Female sexual dysfunction also appears to be positively correlated with obesity, although the literature is less clear as to the extent to which this is true. Despite a scarcity of relevant data, preliminary evidence indicates that weight loss improves sexual function in men and women. Obesity is associated with an increased incidence of benign prostatic hyperplasia and subsequent lower urinary tract symptoms in men, as well as an increased incidence of stress urinary incontinence in women. Despite a lack of relevant data, there is preliminary evidence that stress urinary incontinence and benign prostatic hyperplasia may be reversible after weight loss. Conclusions: Despite the abundant evidence that indicates a correlation between obesity and several urological diseases, there is a paucity of data regarding the effects of long-term weight loss on these conditions. However, the preliminary data indicate that the detrimental effects of obesity are reversible, and that long-term weight loss may decrease the incidence and severity of urological disease. Therefore, further research is needed to elucidate the impact of longterm surgical and medical weight loss on urolithiasis, lower urinary tract symptoms and incontinence, and sexual dysfunction. Key Words: urolithiasis; bariatric surgery; sexual dysfunction, physiological; prostatic hyperplasia; urinary incontinence
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0022-5347/09/1816-2424/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 181, 2424-2429, June 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.01.107
OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
BODY mass index, the preferred metric used in clinical settings to evaluate obesity, is calculated as weight (kg) divided by height squared (m2). In 2000 the WHO published a classification system for overweight and obesity based on BMI (see table).1 In the last 15 years there has been a staggering increase in the prevalence of obesity in the United States. In 1991 the Centers for Disease Control Behavioral Risk Factor Surveillance System reported that 4 states had an obesity prevalence rate of 15% to 19% and that no state had a rate greater than 20%. By the year 2000 the prevalence of obesity was greater than 20% in 22 states. In 2005 only 4 states had an obesity prevalence rate of less than 20%, while 17 states had a prevalence rate of 25% or greater, including with 3 with a rate of 30% or greater.2 Obesity is a significant risk factor for metabolic syndrome, a descriptor for a clustering of risk factors including hypertension, hypertriglyceridemia, decreased high density lipoprotein and insulin resistance. It is also associated with several cardiovascular, gastrointestinal, respiratory, musculoskeletal, neurological and psychological comorbidities. In 2004 Mydlo reviewed the associations between obesity and a number of urological illnesses, including stress urinary incontinence, lower urinary tract symptoms, erectile dysfunction, infertility, urinary stone formation, renal disease, and cancers of the prostate, kidneys, bladder and testes.3 Additionally, significant improvements in obesity related comorbidities have been observed after longterm weight loss. In 2006 Bouldin et al reviewed the effects of surgical therapy for morbid obesity on type II diabetes, hypertension, dyslipidemia, metabolic syndrome, sleep apnea, asthma, gastroesophageal reflux disease, degenerative joint disease and urinary incontinence.4 All were significantly ameliorated with surgical weight loss therapy. We review the effects of obesity and long-term weight loss on nononcological urological disease, particularly urinary stone formation, erectile dysfunction, female sexual dysfunction, voiding dysfunction, and urinary incontinence.
BMI classifications outlined by the WHO BMI
Classification
Less than 18.5 18.5–24.9 25–29.9 30–34.9 35–39.9 Greater than 40
Underweight Normal weight Overweight (pre-obese) Obese class I Obese class II Obese class III (morbidly obese)
A patient with a BMI of 30 to 39.9 and 1 or more significant comorbidities is sometimes classified as morbidly obese.
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MATERIALS AND METHODS A literature search was conducted using Ovid’s MEDLINE, accessed through Emory University’s Health Sciences Library website. The subject headings obesity, weight loss surgery, urolithiasis, sexual dysfunction, erectile dysfunction, benign prostatic hyperplasia and urinary incontinence were used as indices for the search. Articles published earlier than 10 years before the time of the literature review (performed in summer of 2007) were not used.
RESULTS AND DISCUSSION Urinary Stone Formation Several studies have indicated an association between obesity and increased urinary excretion of several electrolytes, as well as an inverse association between BMI and urinary pH. Increased urinary excretion of calcium, oxalate and uric acid can lead to supersaturation of these substances and subsequent formation of calcium oxalate stones. As urinary pH decreases, uric acid becomes more insoluble and precipitates out to crystallize into stones. Taylor and Curhan studied data from the cohorts in the Health Professionals Follow-Up Study and the Nurses’ Health Studies I and II, and observed a positive relationship between BMI and urinary excretion of calcium, oxalate, citrate, uric acid, sodium, potassium and phosphate.5 Urinary pH decreased with increased BMI. Taylor et al further determined that in each cohort there was a significant association between increased BMI and relative risk of developing symptomatic urinary stones.6 Siener et al studied 527 calcium oxalate stone formers and found a positive relationship between BMI and urinary excretion of uric acid, sodium, ammonium and phosphate, as well as an inverse relationship between BMI and urinary pH.7 Likewise, Powell et al retrospectively evaluated 5,942 patients with urinary stone disease and observed that those patients classified as obese had increased urinary excretion of calcium, oxalate and uric acid, as well as a decreased urinary pH. Additionally, the mean number of stone episodes was greater in obese vs nonobese women (3.38 and 2.98, respectively) but not significantly different in obese vs nonobese men (3.55 and 3.56, respectively).8 Most recently Yun et al studied 153 patients who presented with a first time stone episode and found that obesity was significantly correlated with recurrent stone formation.9 Ekeruo et al retrospectively reviewed the metabolic risk factors for obese stone formers and the response to dietary and medical therapy.10 That cohort was compared to a group of age and sex matched nonobese stone formers. Uric acid stones accounted for 63% of stones formed in 83 obese patients analyzed compared to only 11% of
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OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
those in the nonobese patients. After directed dietary and medical therapy the obese patient group demonstrated a decrease in new stone formation from 1.8 to 0.2 stones formed per patient per year and the nonobese patients showed a similar decrease from 1.7 to 0.1. The effects of bariatric surgery on urinary stone formation and risk factors have not been demonstrated extensively in the literature. This relationship is becoming increasingly more important as the number of bariatric surgeries has dramatically increased in the last decade, with an estimated 177,600 cases performed in 2006.11 Several studies have demonstrated that bariatric surgery results in significant hyperoxaluria. Palomar et al studied 35 morbidly obese patients who underwent biliopancreatic diversion surgery for weight loss, and observed decreased urinary calcium and citrate excretion but increased oxalate excretion 1 year postoperatively.12 Pedro et al studied 13 patients who underwent laparoscopic Roux-en-Y gastric bypass surgery and found an increased risk of hyperoxaluria and supersaturation of calcium oxalate 3 months after surgery.13 Asplin and Coe compared urine chemistry profiles of 132 patients with nephrolithiasis who underwent jejunoileal bypass or bariatric surgery (gastric banding or bypass procedures).14 Patients who underwent either surgery showed a significantly increased incidence of hyperoxaluria compared to that in other urinary stone formers who had not undergone surgery. Sinha et al studied 60 patients who underwent Roux-en-Y gastric bypass and in whom urinary stones subsequently developed.15 Calcium oxalate supersaturation was significantly increased while uric acid supersaturation was decreased. The authors hypothesized that fat malabsorption reduced calcium absorption, which in turn led to larger amounts of uncomplexed oxalate being delivered to the colon (enteric hyperoxaluria). However, not all studies have demonstrated an association between bariatric surgery and hyperoxaluria. Leitao et al studied 1,726 morbidly obese patients who underwent Roux-en-Y gastric bypass and found no correlation between the procedure and risk of urinary stone formation.16 In summary, there is ample evidence to support an increased risk of urolithiasis in obese patients. The effects of long-term weight loss are not as immediately apparent. Intestinal bypass surgeries, which cause significant malabsorption, may lead to hyperoxaluria and increase subsequent stone formation. At this time it is unclear whether the decreased food intake associated with bariatric procedures may negate these risks and actually lower stone risk in the long term. Similarly the effects of medical weight loss on stone risk have not been extensively investigated. Clearly further studies are needed to
elucidate the overall impact that bariatric procedures and other weight loss options have on the formation of urinary stones. Sexual Dysfunction It is well-known that obesity is associated with an increased risk of ED but the extent to which it may be correlated with female sexual dysfunction is unclear. Larsen et al reviewed the literature and found obesity to be strongly associated with ED in prospective and cross sectional studies.17 However, only 1 study described obesity and female sexual dysfunction, and found that there was no significant association. Several other studies have shown a positive association between BMI and ED.18 Bacon et al conducted a prospective study and found that the relative risk of incident erectile dysfunction during a 14-year followup was 1.99 for obese men.19 Corona et al studied this association and determined that obese men had more severe ED and hypogonadism, which can further exacerbate sexual dysfunction, than nonobese men.20 Additionally, they found higher levels of anxiety in obese men and hypothesized that the somatization of this anxiety was a factor in the increased risk of ED. The cause and effect relationship between hypogonadism in men (ie low testosterone) and the metabolic syndrome is controversial. Recent studies have indicated that a relative androgen deficiency may predict the development of insulin resistance and that supplementing testosterone can improve the metabolic profile in obese men.21 Other studies have indicated that supplementation of testosterone has a role in weight loss and decreasing plasma lipid levels but has no direct effect on insulin sensitivity.22 In 2005 Chen et al reviewed the relationship between plasma androgen levels, obesity and metabolic profile, and found it likely that in the obesityhypogonadism association obesity was likely to be the causative factor for decreasing testosterone in men.23 The association between low testosterone (particularly in older men) and the development of ED is well-known. Thus, it would be expected that significant weight loss would help to improve sexual dysfunction in men. The relationship between female sexual dysfunction and obesity has not been as well documented, although a study by Kolotkin et al indicated that higher BMI was associated with higher impairment in sexual quality of life in women, as measured by the Impact of Weight on Quality of Life-Lite questionnaire.24 Long-term weight loss appears to have a positive impact on male and female sexual dysfunction. Esposito et al conducted a 2-year clinical trial in which 110 obese men were randomized to an intervention group given detailed advice about how to achieve significant weight loss or a control group given more
OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
general information regarding weight loss. After 2 years mean BMI decreased from 36.9 to 31.2 in the intervention group compared to a less dramatic decrease from 36.4 to 35.7 in controls. The International Index of Erectile Function was used to assess the level of sexual dysfunction in each group. Mean International Index of Erectile Function score improved in the intervention group (13.9 to 17) but remained stable in the control group (13.5 to 13.6).25 However, Derby et al prospectively followed a cohort of men 40 to 70 years old during an 8-year period and found that baseline obesity was significantly associated with an increased risk of ED regardless of followup weight loss.26 Female sexual function also appears to improve with long-term weight loss. Kinzl et al studied the effects of gastric banding surgery on the sexual attitudes of 82 morbidly obese women, and found that 63% stated that they enjoyed sex more and 20% reported that their partnership had improved after losing weight.27 Kim et al conducted a clinical trial in which 46 overweight and obese women were randomized to an intervention group who received behavioral therapy and the selective serotonin reuptake inhibitor sibutramine for weight loss, and a control group who received only behavioral therapy. After 8 weeks the mean weight loss was 6.03% in the intervention group vs 0.38% in the control group. The Female Sexual Function Index was used to assess the level of sexual dysfunction in each group. Mean Female Sexual Function Index score improved 1.37 points in the intervention group and decreased 0.93 points in the control group (p ⬍0.05).28 In summary, the incidence and severity of ED increase with obesity in men. Female sexual disorders also appear to be greater in obese women, although this is more difficult to measure. However, there is convincing preliminary evidence that weight loss improves sexual function in both sexes. Voiding Dysfunction/Incontinence Several studies have correlated obesity with various urinary disorders. In men abdominal obesity has been demonstrated to be associated with increased incidence and severity of BPH and its associated urinary symptoms.29 –31 The exact mechanism by which obesity leads to increased prostate volume is not clear but proposed causative factors include increased estrogen/testosterone, fasting glucose and hyperinsulinemia in obese men compared to those in men of normal weight. Additionally, obesity has been associated with increased nocturia in women and to a lesser extent in men. Tikkinen et al performed a population based study to analyze the association of nocturia with overweight and obesity in 6,000 Finnish men and women.32 The age standardized attributable fraction of increased BMI for
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nocturia was 17.7% in men and 18.5% in women (p ⬍0.001). Obesity has also been demonstrated to be correlated with increased intra-abdominal pressure, which produces increased bladder pressure and can lead to stress urinary incontinence. Sugerman et al studied 84 anesthetized patients before gastric bypass surgery and found that bladder pressure was greater in obese than nonobese patients (18 vs 7 cm H2O, respectfully, p ⬍0.001).33 McGrother et al prospectively studied a cohort of 12,570 women and found that obese women had significantly higher odds of developing stress urinary incontinence (longitudinal OR 2.3, p ⬍0.001).34 Long-term weight loss has been shown to have a significant effect on bladder pressure and urinary incontinence.4 Subak et al conducted a clinical trial in which 48 overweight and obese women were randomized to an intervention group consisting of a 3-month liquid diet weight reduction program or a control group.35 After 3 months the weight loss group experienced a 60% reduction in urinary incontinence episodes compared to a 15% reduction in the control group. Surgically induced weight loss has shown similar effects. Sugerman studied 15 morbidly obese patients who underwent gastric bypass surgery and observed a mean decrease in bladder pressure from 17 to 10 cm H2O 1 year after surgery.36 Furthermore, while 7 patients complained of incontinence episodes before surgery, none reported incontinence after surgery. Similarly Bump et al studied 13 patients undergoing surgically induced weight loss and found that while 12 of these women experienced incontinence episodes before surgery, only 1 reported issues with incontinence after surgery (p ⬍0.004).37 Finally, Kristal et al examined risk factors for BPH, which was assessed using the International Prostate Symptom Score.38 They studied 5,667 patients in the placebo arm of a prostate cancer trial and found that each 0.05 increase in waist-to-hip ratio (a measure of central obesity) was associated with a 10% increased risk of total and severe BPH (p ⬍0.003 and ⬍0.02, respectively). The authors suggested that weight loss could be helpful in the treatment and prevention of BPH and its associated urinary symptoms. In summary, obesity is associated with an increased incidence of BPH and lower urinary tract symptoms in men and urinary incontinence in women. The effects of long-term weight loss on urinary comorbidities have not been studied to a great extent, although there is preliminary evidence that stress urinary incontinence and BPH may be reversible after weight loss. There is a need for more research into the effects of medically and surgically induced weight loss on urinary disorders including weak stream, increased frequency/urgency and nocturia.
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OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
CONCLUSIONS Obesity has reached epidemic proportions in the United States as well as the rest of the world. This rapidly increasing prevalence of obesity should be concerning to urologists due to the number of urological comorbidities with which it is associated, including but not limited to urolithiasis, erectile dysfunction, female sexual dysfunction, BPH, nocturia and stress urinary incontinence. More importantly however, preliminary data indicate that these detrimental effects of obesity are reversible, and that the incidence and severity of these urological conditions may be significantly reduced by long-term weight loss. Further research is still needed to elucidate the impact of long-term surgically and medically induced weight loss on urolithiasis, sexual dysfunction and lower urinary tract symptoms/incontinence. Urologists may be able to have a significant role in reducing the prevalence of urological disease by helping obese patients develop and implement a long-term weight loss strategy. The importance of a balanced, healthier diet consisting of moderately sized meals with more fruits, vegetables, nuts and whole grains, and reduced intake of sugars and fats should be stressed. The Dietary Guidelines for Americans recommends creating an energy deficit of 500 kcal/day to achieve optimal weight loss.39 Recently Carels et al performed a randomized clinical trial in which they investigated the effects of following these recommendations on weight loss during a 14-week period.40 Individuals who averaged an energy deficit of at least 500 kcal per day lost nearly 4 times as
much weight as those who had a deficit of less than the recommended amount. The Weight Loss Maintenance trial, a 4-center randomized trial designed to improve methods for long-term weight maintenance, was conducted during a 30-month period. The results of the initial 6 months of the study were recently published.41 Several recommendations were made for overweight and obese patients to maximize weight loss, including consume approximately 500 fewer kcal each day, exercise a total of 180 minutes each week, keep daily records of food and exercise habits, eat 9 to 12 servings of fruit daily, eat 2 to 3 servings of low fat dairy foods daily, limit fats to 25% or less of daily caloric intake, eat 2,400 mg or less of sodium daily and limit alcoholic intake to 1 drink per day for women or 2 drinks per day for men. The study subjects demonstrated an average weight loss of 13 pounds in the first 6 months of the study, which was determined to be a clinically significant short-term weight loss. This information is provided primarily as an introduction to current dietary and behavioral recommendations for achieving long-term weight loss. It is unrealistic to expect urologists to micromanage patient diets and exercise regimens. However, given the significant association of obesity with urological disease, urologists should be prepared to offer simple dietary guidelines for patients to follow and recommend a nutritionist or dietician for further weight loss management. These simple interventional steps should ultimately reduce the incidence of urological disease in the patient population.
REFERENCES 1. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organization Technical Report Series, 894. Geneva: World Health Organization 2007; pp i–xii. 2. CDC: Behavioral Risk Factor Surveillance System. Available at www.cdc.gov/brfss. Accessed January 19, 2009. 3. Mydlo JH: The impact of obesity in urology. Urol Clin North Am 2004; 31: 275. 4. Bouldin MJ, Ross LA, Sumrall CD, Loustalot FV, Low AK and Land KK: The effect of obesity surgery on obesity comorbidity. Am J Med Sci 2006; 331: 183.
7. Siener R, Glatz S, Nicolay C and Hesse A: The role of overweight and obesity in calcium oxalate stone formation. Obes Res 2004; 12: 106. 8. Powell CR, Stoller ML, Schwartz BF, Kane C, Gentle DL, Bruce JE et al: Impact of body weight on urinary electrolytes in urinary stone formers. Urology 2000; 55: 825. 9. Yun SJ, Ha Y-S, Kim TH, Kim Y-J, Lee S-C and Kim WJ: Obesity and phosphaturia as the important predictors for recurrence in first-time urinary stone formers. J Urol, suppl., 2007; 177: 452, abstract 1369.
12. Palomar R, Fernandez-Fresnedo G, DominguezDiez A, Lopez-Deogracias M, Olmedo F, Martin de Francisco AL et al: Effects of weight loss after biliopancreatic diversion on metabolism and cardiovascular profile. Obes Surg 2005; 15: 794. 13. Pedro RN, Duffey B, Weiland D, Melquist J, Kriedberg C, Ikramuddin S et al: Impact of bariatric surgery on urinary stone risk factors in the morbidly obese. J Urol, suppl., 2007; 177: 451, abstract 1367. 14. Asplin JR and Coe FL: Hyperoxaluria in kidney stone formers treated with modern bariatric surgery. J Urol 2007; 177: 565.
5. Taylor EN and Curhan GC: Body size and 24-hour urine composition. Am J Kidney Dis 2006; 48: 905.
10. Ekeruo WO, Tan YH, Young MD, Dahm P, Maloney ME, Mathias BJ et al: Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients. J Urol 2004; 172: 159.
15. Sinha MK, Collazo-Clavell ML, Rule A, Milliner DS, Nelson W, Sarr MG et al: Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney Int 2007; 72: 100.
6. Taylor EN, Stampfer MJ and Curhan GC: Obesity, weight gain, and the risk of kidney stones. JAMA 2005; 293: 455.
11. American Society for Metabolic and Bariatric Surgery. Available at www.asbs.org. Accessed January 19, 2009.
16. Leitao VA, Mutafyan G, Haleblian GE, Robinson MR, Pierre SA, Pryor A et al: Correlation between stone formation and weight loss after Roux-en-Y
OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
gastric bypass. J Urol, suppl., 2007; 177: 450, abstract 1366. 17. Larsen SH, Wagner G and Heitmann BL: Sexual function and obesity. Int J Obes 2007; 31: 1189. 18. Muller A and Mulhall JP: Cardiovascular disease, metabolic syndrome and erectile dysfunction. Curr Opin Urol 2006; 16: 435. 19. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB and Rimm EB: A prospective study of risk factors for erectile dysfunction. J Urol 2006; 176: 217. 20. Corona G, Mannucci E, Schulman C, Petrone L, Mansani R, Cilotti A et al: Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. Eur Urol 2006; 50: 595. 21. Boyanov MA, Boneva Z and Christov VG: Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6: 1. 22. Liu PY, Wishart SM, Celermajer DS, Jimenez M, Pierro ID, Conway AJ et al: Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin. Eur J Endocrinol 2003; 148: 55. 23. Chen RYT, Wittert GA and Andrews GR: Relative androgen deficiency in relation to obesity and metabolic status in older men. Diabetes Obes Metab 2006; 8: 429. 24. Kolotkin RL, Binks M, Crosby RD, Ostbye T, Gress RE and Adams TD: Obesity and sexual quality of life. Obesity 2006; 14: 472.
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25. Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F et al: Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004; 291: 2978.
34. McGrother CW, Donaldson MMK, Hayward T, Matthews R, Dallosso HM, Hyde C et al: Urinary storage symptoms and comorbidities: a prospective population cohort study in middle-aged and older women. Age Ageing 2006; 35: 16.
26. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB and McKinlay JB: Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology 2000; 56: 302.
35. Subak LL, Whitcomb E, Shen H, Saxton J, Vittinghoff E and Brown JS: Weight loss: a novel and effective treatment for urinary incontinence. J Urol 2005; 174: 190.
27. Kinzl JF, Trefalt E, Fiala M, Hotter A, Biebl W and Aigner F: Partnership, sexuality, and sexual disorders in morbidly obese women: consequences of weight loss after gastric banding. Obes Surg 2001; 11: 455.
36. Sugerman HJ: Effects of increased intra-abdominal pressure in severe obesity. Surg Clin North Am 2001; 81: 1063.
28. Kim KK, Kang HC, Kim SS and Youn BB: Influence of weight reduction by sibutramine on female sexual function. Int J Obes 2006; 30: 758. 29. Lee S, Min HG, Choi SH, Kim YJ, Oh SW, Kim YJ et al: Central obesity as a risk factor for prostatic hyperplasia. Obesity 2006; 14: 172. 30. Parsons JK, Carter HB, Partin AW, Windham BG, Metter EJ, Ferrucci L et al: Metabolic factors associated with benign prostatic hyperplasia. J Clin Endocrinol Metab 2006; 91: 2562. 31. Xie L-P, Bai Y, Zhang X-Z, Zheng X-Y, Yao K-S, Xu L et al: Obesity and benign prostatic enlargement: a large observational study in China. Urology 2007; 69: 680. 32. Tikkinen KA, Auvinen A, Huhtala H and Tammela TLJ: Nocturia and obesity: a population-based study in Finland. Am J Epidemiol 2006; 163: 1003. 33. Sugerman H, Windsor A, Bessos M and Wolfe L: Intra-abdominal pressure, sagittal abdominal diameter and obesity comorbidity. J Int Med 1997; 241: 71.
37. Bump RC, Sugerman HJ, Fantl JA and McClish DK: Obesity and lower urinary tract function in women: effect of surgically induced weight loss. Am J Obstet Gynecol 1992; 167: 392. 38. Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Weiss N, Goodman P et al: Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial. J Urol 2007; 177: 1395. 39. U.S. Department of Health and Human Service USDoA: Dietary Guidelines for Americans, 6th ed. Washington, D. C.: Government Printing Office 2005. 40. Carels RA, Young KM, Coit C, Clayton AM, Spencer A and Hobbs M: Can following the caloric restriction recommendations from the Dietary Guidelines for Americans help individuals lose weight? Eat Behav 2008; 9: 328. 41. Hollis JF, Gullion CM, Stevens VJ, Brantley PJ, Appel LJ, Ard JD et al: Weight loss during the intensive intervention phase of the weight-loss maintenance trial. Am J Prev Med 2008; 35: 118.
Effects of Obesity and Weight Loss in Patients With Nononcological Urological Disease Vivek Natarajan,*,† Viraj Master† and Kenneth Ogan‡ From the Department of Urology, Emory University School of Medicine, Atlanta, Georgia
Abbreviations and Acronyms BMI ⫽ body mass index BPH ⫽ benign prostatic hyperplasia ED ⫽ erectile dysfunction Submitted for publication August 29, 2008. * Correspondence: The Emory Clinic, Department of Urology, 1365 Clifton Rd., Suite B, Atlanta, Georgia 30322 (telephone: 404-778-3038; FAX: 404-778-4006; e-mail [email protected]). † Nothing to disclose. ‡ Financial interest and/or other relationship with Cook Urological.
Editor’s Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 2834 and 2835.
Purpose: We reviewed the effects of obesity and long-term weight loss on nononcological urological disease, particularly urinary stone formation, erectile dysfunction, female sexual dysfunction, voiding dysfunction and urinary incontinence. Materials and Methods: A literature search was conducted using Ovid’s MEDLINE®, accessed through Emory University’s Health Sciences Library web site. The subject headings obesity, weight loss surgery, urolithiasis, sexual dysfunction, erectile dysfunction, benign prostatic hyperplasia and urinary incontinence were used as indices for the search. Articles published earlier than 10 years before the literature review (performed in summer of 2007) were not used. Results: There is ample evidence to support an increased risk of urolithiasis in obese patients. However, the effects of long-term weight loss on urinary stone formation have not been studied as extensively in the literature. It is unclear whether the decreased food intake after surgical weight loss procedures may negate the associated risk of malabsorption and decrease the risk of urolithiasis in the long term. The incidence and severity of erectile dysfunction in men increase with obesity. Female sexual dysfunction also appears to be positively correlated with obesity, although the literature is less clear as to the extent to which this is true. Despite a scarcity of relevant data, preliminary evidence indicates that weight loss improves sexual function in men and women. Obesity is associated with an increased incidence of benign prostatic hyperplasia and subsequent lower urinary tract symptoms in men, as well as an increased incidence of stress urinary incontinence in women. Despite a lack of relevant data, there is preliminary evidence that stress urinary incontinence and benign prostatic hyperplasia may be reversible after weight loss. Conclusions: Despite the abundant evidence that indicates a correlation between obesity and several urological diseases, there is a paucity of data regarding the effects of long-term weight loss on these conditions. However, the preliminary data indicate that the detrimental effects of obesity are reversible, and that long-term weight loss may decrease the incidence and severity of urological disease. Therefore, further research is needed to elucidate the impact of longterm surgical and medical weight loss on urolithiasis, lower urinary tract symptoms and incontinence, and sexual dysfunction. Key Words: urolithiasis; bariatric surgery; sexual dysfunction, physiological; prostatic hyperplasia; urinary incontinence
2424
www.jurology.com
0022-5347/09/1816-2424/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 181, 2424-2429, June 2009 Printed in U.S.A. DOI:10.1016/j.juro.2009.01.107
OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
BODY mass index, the preferred metric used in clinical settings to evaluate obesity, is calculated as weight (kg) divided by height squared (m2). In 2000 the WHO published a classification system for overweight and obesity based on BMI (see table).1 In the last 15 years there has been a staggering increase in the prevalence of obesity in the United States. In 1991 the Centers for Disease Control Behavioral Risk Factor Surveillance System reported that 4 states had an obesity prevalence rate of 15% to 19% and that no state had a rate greater than 20%. By the year 2000 the prevalence of obesity was greater than 20% in 22 states. In 2005 only 4 states had an obesity prevalence rate of less than 20%, while 17 states had a prevalence rate of 25% or greater, including with 3 with a rate of 30% or greater.2 Obesity is a significant risk factor for metabolic syndrome, a descriptor for a clustering of risk factors including hypertension, hypertriglyceridemia, decreased high density lipoprotein and insulin resistance. It is also associated with several cardiovascular, gastrointestinal, respiratory, musculoskeletal, neurological and psychological comorbidities. In 2004 Mydlo reviewed the associations between obesity and a number of urological illnesses, including stress urinary incontinence, lower urinary tract symptoms, erectile dysfunction, infertility, urinary stone formation, renal disease, and cancers of the prostate, kidneys, bladder and testes.3 Additionally, significant improvements in obesity related comorbidities have been observed after longterm weight loss. In 2006 Bouldin et al reviewed the effects of surgical therapy for morbid obesity on type II diabetes, hypertension, dyslipidemia, metabolic syndrome, sleep apnea, asthma, gastroesophageal reflux disease, degenerative joint disease and urinary incontinence.4 All were significantly ameliorated with surgical weight loss therapy. We review the effects of obesity and long-term weight loss on nononcological urological disease, particularly urinary stone formation, erectile dysfunction, female sexual dysfunction, voiding dysfunction, and urinary incontinence.
BMI classifications outlined by the WHO BMI
Classification
Less than 18.5 18.5–24.9 25–29.9 30–34.9 35–39.9 Greater than 40
Underweight Normal weight Overweight (pre-obese) Obese class I Obese class II Obese class III (morbidly obese)
A patient with a BMI of 30 to 39.9 and 1 or more significant comorbidities is sometimes classified as morbidly obese.
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MATERIALS AND METHODS A literature search was conducted using Ovid’s MEDLINE, accessed through Emory University’s Health Sciences Library website. The subject headings obesity, weight loss surgery, urolithiasis, sexual dysfunction, erectile dysfunction, benign prostatic hyperplasia and urinary incontinence were used as indices for the search. Articles published earlier than 10 years before the time of the literature review (performed in summer of 2007) were not used.
RESULTS AND DISCUSSION Urinary Stone Formation Several studies have indicated an association between obesity and increased urinary excretion of several electrolytes, as well as an inverse association between BMI and urinary pH. Increased urinary excretion of calcium, oxalate and uric acid can lead to supersaturation of these substances and subsequent formation of calcium oxalate stones. As urinary pH decreases, uric acid becomes more insoluble and precipitates out to crystallize into stones. Taylor and Curhan studied data from the cohorts in the Health Professionals Follow-Up Study and the Nurses’ Health Studies I and II, and observed a positive relationship between BMI and urinary excretion of calcium, oxalate, citrate, uric acid, sodium, potassium and phosphate.5 Urinary pH decreased with increased BMI. Taylor et al further determined that in each cohort there was a significant association between increased BMI and relative risk of developing symptomatic urinary stones.6 Siener et al studied 527 calcium oxalate stone formers and found a positive relationship between BMI and urinary excretion of uric acid, sodium, ammonium and phosphate, as well as an inverse relationship between BMI and urinary pH.7 Likewise, Powell et al retrospectively evaluated 5,942 patients with urinary stone disease and observed that those patients classified as obese had increased urinary excretion of calcium, oxalate and uric acid, as well as a decreased urinary pH. Additionally, the mean number of stone episodes was greater in obese vs nonobese women (3.38 and 2.98, respectively) but not significantly different in obese vs nonobese men (3.55 and 3.56, respectively).8 Most recently Yun et al studied 153 patients who presented with a first time stone episode and found that obesity was significantly correlated with recurrent stone formation.9 Ekeruo et al retrospectively reviewed the metabolic risk factors for obese stone formers and the response to dietary and medical therapy.10 That cohort was compared to a group of age and sex matched nonobese stone formers. Uric acid stones accounted for 63% of stones formed in 83 obese patients analyzed compared to only 11% of
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those in the nonobese patients. After directed dietary and medical therapy the obese patient group demonstrated a decrease in new stone formation from 1.8 to 0.2 stones formed per patient per year and the nonobese patients showed a similar decrease from 1.7 to 0.1. The effects of bariatric surgery on urinary stone formation and risk factors have not been demonstrated extensively in the literature. This relationship is becoming increasingly more important as the number of bariatric surgeries has dramatically increased in the last decade, with an estimated 177,600 cases performed in 2006.11 Several studies have demonstrated that bariatric surgery results in significant hyperoxaluria. Palomar et al studied 35 morbidly obese patients who underwent biliopancreatic diversion surgery for weight loss, and observed decreased urinary calcium and citrate excretion but increased oxalate excretion 1 year postoperatively.12 Pedro et al studied 13 patients who underwent laparoscopic Roux-en-Y gastric bypass surgery and found an increased risk of hyperoxaluria and supersaturation of calcium oxalate 3 months after surgery.13 Asplin and Coe compared urine chemistry profiles of 132 patients with nephrolithiasis who underwent jejunoileal bypass or bariatric surgery (gastric banding or bypass procedures).14 Patients who underwent either surgery showed a significantly increased incidence of hyperoxaluria compared to that in other urinary stone formers who had not undergone surgery. Sinha et al studied 60 patients who underwent Roux-en-Y gastric bypass and in whom urinary stones subsequently developed.15 Calcium oxalate supersaturation was significantly increased while uric acid supersaturation was decreased. The authors hypothesized that fat malabsorption reduced calcium absorption, which in turn led to larger amounts of uncomplexed oxalate being delivered to the colon (enteric hyperoxaluria). However, not all studies have demonstrated an association between bariatric surgery and hyperoxaluria. Leitao et al studied 1,726 morbidly obese patients who underwent Roux-en-Y gastric bypass and found no correlation between the procedure and risk of urinary stone formation.16 In summary, there is ample evidence to support an increased risk of urolithiasis in obese patients. The effects of long-term weight loss are not as immediately apparent. Intestinal bypass surgeries, which cause significant malabsorption, may lead to hyperoxaluria and increase subsequent stone formation. At this time it is unclear whether the decreased food intake associated with bariatric procedures may negate these risks and actually lower stone risk in the long term. Similarly the effects of medical weight loss on stone risk have not been extensively investigated. Clearly further studies are needed to
elucidate the overall impact that bariatric procedures and other weight loss options have on the formation of urinary stones. Sexual Dysfunction It is well-known that obesity is associated with an increased risk of ED but the extent to which it may be correlated with female sexual dysfunction is unclear. Larsen et al reviewed the literature and found obesity to be strongly associated with ED in prospective and cross sectional studies.17 However, only 1 study described obesity and female sexual dysfunction, and found that there was no significant association. Several other studies have shown a positive association between BMI and ED.18 Bacon et al conducted a prospective study and found that the relative risk of incident erectile dysfunction during a 14-year followup was 1.99 for obese men.19 Corona et al studied this association and determined that obese men had more severe ED and hypogonadism, which can further exacerbate sexual dysfunction, than nonobese men.20 Additionally, they found higher levels of anxiety in obese men and hypothesized that the somatization of this anxiety was a factor in the increased risk of ED. The cause and effect relationship between hypogonadism in men (ie low testosterone) and the metabolic syndrome is controversial. Recent studies have indicated that a relative androgen deficiency may predict the development of insulin resistance and that supplementing testosterone can improve the metabolic profile in obese men.21 Other studies have indicated that supplementation of testosterone has a role in weight loss and decreasing plasma lipid levels but has no direct effect on insulin sensitivity.22 In 2005 Chen et al reviewed the relationship between plasma androgen levels, obesity and metabolic profile, and found it likely that in the obesityhypogonadism association obesity was likely to be the causative factor for decreasing testosterone in men.23 The association between low testosterone (particularly in older men) and the development of ED is well-known. Thus, it would be expected that significant weight loss would help to improve sexual dysfunction in men. The relationship between female sexual dysfunction and obesity has not been as well documented, although a study by Kolotkin et al indicated that higher BMI was associated with higher impairment in sexual quality of life in women, as measured by the Impact of Weight on Quality of Life-Lite questionnaire.24 Long-term weight loss appears to have a positive impact on male and female sexual dysfunction. Esposito et al conducted a 2-year clinical trial in which 110 obese men were randomized to an intervention group given detailed advice about how to achieve significant weight loss or a control group given more
OBESITY AND WEIGHT LOSS IN UROLOGICAL DISEASE
general information regarding weight loss. After 2 years mean BMI decreased from 36.9 to 31.2 in the intervention group compared to a less dramatic decrease from 36.4 to 35.7 in controls. The International Index of Erectile Function was used to assess the level of sexual dysfunction in each group. Mean International Index of Erectile Function score improved in the intervention group (13.9 to 17) but remained stable in the control group (13.5 to 13.6).25 However, Derby et al prospectively followed a cohort of men 40 to 70 years old during an 8-year period and found that baseline obesity was significantly associated with an increased risk of ED regardless of followup weight loss.26 Female sexual function also appears to improve with long-term weight loss. Kinzl et al studied the effects of gastric banding surgery on the sexual attitudes of 82 morbidly obese women, and found that 63% stated that they enjoyed sex more and 20% reported that their partnership had improved after losing weight.27 Kim et al conducted a clinical trial in which 46 overweight and obese women were randomized to an intervention group who received behavioral therapy and the selective serotonin reuptake inhibitor sibutramine for weight loss, and a control group who received only behavioral therapy. After 8 weeks the mean weight loss was 6.03% in the intervention group vs 0.38% in the control group. The Female Sexual Function Index was used to assess the level of sexual dysfunction in each group. Mean Female Sexual Function Index score improved 1.37 points in the intervention group and decreased 0.93 points in the control group (p ⬍0.05).28 In summary, the incidence and severity of ED increase with obesity in men. Female sexual disorders also appear to be greater in obese women, although this is more difficult to measure. However, there is convincing preliminary evidence that weight loss improves sexual function in both sexes. Voiding Dysfunction/Incontinence Several studies have correlated obesity with various urinary disorders. In men abdominal obesity has been demonstrated to be associated with increased incidence and severity of BPH and its associated urinary symptoms.29 –31 The exact mechanism by which obesity leads to increased prostate volume is not clear but proposed causative factors include increased estrogen/testosterone, fasting glucose and hyperinsulinemia in obese men compared to those in men of normal weight. Additionally, obesity has been associated with increased nocturia in women and to a lesser extent in men. Tikkinen et al performed a population based study to analyze the association of nocturia with overweight and obesity in 6,000 Finnish men and women.32 The age standardized attributable fraction of increased BMI for
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nocturia was 17.7% in men and 18.5% in women (p ⬍0.001). Obesity has also been demonstrated to be correlated with increased intra-abdominal pressure, which produces increased bladder pressure and can lead to stress urinary incontinence. Sugerman et al studied 84 anesthetized patients before gastric bypass surgery and found that bladder pressure was greater in obese than nonobese patients (18 vs 7 cm H2O, respectfully, p ⬍0.001).33 McGrother et al prospectively studied a cohort of 12,570 women and found that obese women had significantly higher odds of developing stress urinary incontinence (longitudinal OR 2.3, p ⬍0.001).34 Long-term weight loss has been shown to have a significant effect on bladder pressure and urinary incontinence.4 Subak et al conducted a clinical trial in which 48 overweight and obese women were randomized to an intervention group consisting of a 3-month liquid diet weight reduction program or a control group.35 After 3 months the weight loss group experienced a 60% reduction in urinary incontinence episodes compared to a 15% reduction in the control group. Surgically induced weight loss has shown similar effects. Sugerman studied 15 morbidly obese patients who underwent gastric bypass surgery and observed a mean decrease in bladder pressure from 17 to 10 cm H2O 1 year after surgery.36 Furthermore, while 7 patients complained of incontinence episodes before surgery, none reported incontinence after surgery. Similarly Bump et al studied 13 patients undergoing surgically induced weight loss and found that while 12 of these women experienced incontinence episodes before surgery, only 1 reported issues with incontinence after surgery (p ⬍0.004).37 Finally, Kristal et al examined risk factors for BPH, which was assessed using the International Prostate Symptom Score.38 They studied 5,667 patients in the placebo arm of a prostate cancer trial and found that each 0.05 increase in waist-to-hip ratio (a measure of central obesity) was associated with a 10% increased risk of total and severe BPH (p ⬍0.003 and ⬍0.02, respectively). The authors suggested that weight loss could be helpful in the treatment and prevention of BPH and its associated urinary symptoms. In summary, obesity is associated with an increased incidence of BPH and lower urinary tract symptoms in men and urinary incontinence in women. The effects of long-term weight loss on urinary comorbidities have not been studied to a great extent, although there is preliminary evidence that stress urinary incontinence and BPH may be reversible after weight loss. There is a need for more research into the effects of medically and surgically induced weight loss on urinary disorders including weak stream, increased frequency/urgency and nocturia.
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CONCLUSIONS Obesity has reached epidemic proportions in the United States as well as the rest of the world. This rapidly increasing prevalence of obesity should be concerning to urologists due to the number of urological comorbidities with which it is associated, including but not limited to urolithiasis, erectile dysfunction, female sexual dysfunction, BPH, nocturia and stress urinary incontinence. More importantly however, preliminary data indicate that these detrimental effects of obesity are reversible, and that the incidence and severity of these urological conditions may be significantly reduced by long-term weight loss. Further research is still needed to elucidate the impact of long-term surgically and medically induced weight loss on urolithiasis, sexual dysfunction and lower urinary tract symptoms/incontinence. Urologists may be able to have a significant role in reducing the prevalence of urological disease by helping obese patients develop and implement a long-term weight loss strategy. The importance of a balanced, healthier diet consisting of moderately sized meals with more fruits, vegetables, nuts and whole grains, and reduced intake of sugars and fats should be stressed. The Dietary Guidelines for Americans recommends creating an energy deficit of 500 kcal/day to achieve optimal weight loss.39 Recently Carels et al performed a randomized clinical trial in which they investigated the effects of following these recommendations on weight loss during a 14-week period.40 Individuals who averaged an energy deficit of at least 500 kcal per day lost nearly 4 times as
much weight as those who had a deficit of less than the recommended amount. The Weight Loss Maintenance trial, a 4-center randomized trial designed to improve methods for long-term weight maintenance, was conducted during a 30-month period. The results of the initial 6 months of the study were recently published.41 Several recommendations were made for overweight and obese patients to maximize weight loss, including consume approximately 500 fewer kcal each day, exercise a total of 180 minutes each week, keep daily records of food and exercise habits, eat 9 to 12 servings of fruit daily, eat 2 to 3 servings of low fat dairy foods daily, limit fats to 25% or less of daily caloric intake, eat 2,400 mg or less of sodium daily and limit alcoholic intake to 1 drink per day for women or 2 drinks per day for men. The study subjects demonstrated an average weight loss of 13 pounds in the first 6 months of the study, which was determined to be a clinically significant short-term weight loss. This information is provided primarily as an introduction to current dietary and behavioral recommendations for achieving long-term weight loss. It is unrealistic to expect urologists to micromanage patient diets and exercise regimens. However, given the significant association of obesity with urological disease, urologists should be prepared to offer simple dietary guidelines for patients to follow and recommend a nutritionist or dietician for further weight loss management. These simple interventional steps should ultimately reduce the incidence of urological disease in the patient population.
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