1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
2 Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, NY.
3 Channing Laboratory, Brigham and Womens Hospital, Harvard Medical School, Boston, MA.
4 Department of Nutrition, Harvard School of Public Health, Boston, MA.
5 Department of Epidemiology, Harvard School of Public Health, Boston, MA.
6 The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD.
Received for publication July 11, 2003; accepted for publication October 8, 2003.
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ABSTRACT |
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nutrition surveys; obesity; prostate; surgery; urinary tract
Abbreviations: Abbreviations: BMI, body mass index; LUTS, lower urinary tract symptoms; NHANES III, Third National Health and Nutrition Examination Survey.
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INTRODUCTION |
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Prostate size or prostate growth rate has been found to be positively associated with anthropometric measures such as body mass index (BMI) or waist-to-hip ratio (2), but the associations are less clear for LUTS and noncancer prostate surgery, including transurethral resection of the prostate. Positive associations between anthropometric measures of obesity and LUTS as well as noncancer prostate surgery were observed in one cohort study (3) but not in another (4).
By using data from NHANES III, a nationally representative sample of noninstitutionalized US men (5), we examined cross-sectionally the association between obesity, especially central adiposity, and the frequency of LUTS in men aged 60 years or older. We explored body weight and BMI in early adulthood as well as changes in BMI as risk factors for LUTS and noncancer prostate surgery (as an indicator of more severe symptomatic LUTS).
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MATERIALS AND METHODS |
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Outcome assessment
Men aged 60 years or older were asked about the following symptoms: 1) How many times per night do you usually get up to urinate (pass water)? ("nocturia"); 2) when you urinate (pass water), do you usually feel like you have not completely emptied your bladder? ("incomplete emptying"); 3) do you usually have trouble starting to urinate (pass water)? ("hesitancy"); and 4) has the force of your urinary stream of water decreased over the years? ("weak stream"). Additionally, men were asked whether they had ever had surgery for their prostate not related to cancer ("noncancer prostate surgery").
The four above-mentioned symptoms are components of the American Urological Association symptom index (6), which further includes questions on frequency, intermittence, and urgency. This index discriminates between men with benign prostatic hyperplasia and controls in the clinical setting (6). Because the frequency, intermittence, and urgency symptoms were not assessed in NHANES III, we could not compute the standardized symptom index. Thus, in the present analysis, men were considered LUTS cases if they reported three or four of the symptoms (excluding those men who reported noncancer prostate surgery). Nocturia was included as a symptom when men had to get up at least twice per night. Men who reported ever having had noncancer prostate surgery were considered a separate group of cases. These men are likely those with the most severe or bothersome LUTS. The comparison group consisted of men who did not report any of the four symptoms and who never had noncancer prostate surgery. Because individually these symptoms are not specific for benign prostatic hyperplasia, men who had only one or two symptoms were not considered cases, nor were they included in the comparison group.
Exposure assessment
Self-reported current body weight, body weight at age 25 years, highest body weight ever, and current height were used to calculate BMI (body weight in kilograms divided by the square of height in meters) for each assessed point in life. Current body weight and height were also assessed during a physical examination that was part of NHANES III. However, since only self-reported weight was available for former ages and self-reported and measured current BMI were highly correlated (r = 0.93), we used self-reported current height and body weight to be consistent over time. Results for BMI in which measured height and weight were used gave similar inferences, however. BMI was categorized as <25.0 kg/m2 (normal), 25.029.9 kg/m2 (overweight), and 30.0 kg/m2 (obese). Additionally, we computed change in BMI from age 25 years to the age at interview as well as change in BMI between age 25 years and the highest BMI ever. For BMI increase, we considered men with a small BMI gain, from 0 to 0.99 kg/m2, as the comparison group and created tertiles for men whose BMI gain was
1.00 kg/m2. Current waist and hip circumferences were measured during the physical examination. We divided waist circumferences into three categories: low (<94.0 cm), medium (94.0101.9 cm), and high (
102 cm). The cutpoints have been suggested as indicators for weight management (7).
Statistical analysis
Statistical analyses were performed by using SAS version 8.1 (SAS Institute, Inc., Cary, North Carolina) and SUDAAN software (8). We used sample weights that took into account several features of the NHANES III survey: the specific probabilities of selection for the individual domains that were oversampled as well as nonresponse and differences between the sample and the total US population (5).
For several indicators of body habitus, logistic regression was used to calculate odds ratios and 95 percent confidence intervals for having three or four LUTS or of having had noncancer prostate surgery compared with having no symptoms or surgery. We adjusted for age (in 5-year categories) and race (non-Hispanic Black, non-Hispanic White, Mexican American, other). Including other possible risk factors for LUTS and benign prostatic hyperplasia in the models, such as cigarette smoking (never, former, current), alcohol intake (at least one alcoholic drink per month or less; assessed by using a food frequency questionnaire), frequency of leisure-time moderate and vigorous physical activity (assessed by interview), and energy intake (assessed by using a 24-hour dietary recall), did not substantially alter the results. Trend tests were performed by assigning to each subject the median value for the category of the risk factor in which the subject belonged and modeling this term as a continuous variable, the coefficient for which was evaluated by using the Wald test.
We determined the joint association of waist circumference (<102, 102 cm) and current BMI (<30 or
30 kg/m2) with LUTS or noncancer prostate surgery by entering into the model terms for the combination of the two anthropometric variables; the reference category was normal-to-overweight current BMI and a low-to-medium current waist circumference. We tested for multiplicative interaction by including a cross-product term for waist circumference (<102,
102 cm) and current BMI (<30 or
30 kg/m2) along with the main effect terms for each in the logistic regression model. The statistical significance of the cross-product term was evaluated by using the Wald test. Similar analyses were conducted to examine the joint effects of BMI at age 25 years (using a cutoff point of
25 kg/m2 to ensure a sufficient sample size in each group since men were leaner at age 25 years than they were at the time of the interview) and increase in BMI between age 25 years and the highest BMI ever, and joint effects between BMI at age 25 years and current waist circumference.
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RESULTS |
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We also examined whether the inverse association between BMI at age 25 years and LUTS later in adulthood was modified by current waist circumference (table 4). Compared with men with a normal BMI at age 25 years and a current smaller waist circumferences (<94 cm), men with a low BMI at age 25 years and a larger current waist circumference had an elevated odds of LUTS, whereas men with a higher BMI at age 25 years and a larger waist did not have a higher odds of LUTS. Men with a higher BMI at age 25 years and a smaller waist circumference had a nonsignificantly lower odds of LUTS compared with men with a normal BMI at age 25 years and a lower current waist circumference.
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DISCUSSION |
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We observed a higher prevalence of LUTS among men with a larger waist circumference, which is consistent with results from the Health Professionals Follow-up Study (3), but we did not observe a statistically significant association with current BMI. Haidinger et al. (9) found a positive association between LUTS and waist circumference but no association between LUTS and current BMI or body weight. BMI and waist circumference capture different aspects of adiposity. BMI is the most commonly used indicator of obesity, but it is not a good indicator of body fat distribution and of the amount of body fat itself since it correlates with body fat as well as with lean body mass. The proportion of lean body mass represented by BMI in older men is smaller than in younger men, thus possibly producing differential effects of BMI on hormones by age. In contrast, waist circumference reflects mainly the variation in subcutaneous and visceral abdominal fat (10).
Waist circumference is positively correlated with plasma insulin levels (10), and the association between waist circumference and LUTS could reflect an effect of insulin on the development of LUTS. This explanation is supported by the attenuation of the association between current BMI and LUTS after we mutually adjusted for waist circumference as well as the observation that currently overweight or obese men with a larger waist circumference had an elevated odds of LUTS whereas men with a high BMI but a smaller waist circumference did not. Hammarsten and Högstedt (2), who found a positive association of insulin level with prostate volume and growth, hypothesized that the trophic effect of a high insulin level might induce an enlarged prostate. An increased insulin concentration is also associated with increased sympathetic nervous system activity, which may additionally contribute to LUTS symptoms.
A larger waist circumference is associated with lower testosterone and sex hormone-binding globulin concentrations independently of BMI (11), whereas estradiol seems to increase with increasing adiposity in men (12). A higher ratio of estrogen to testosterone in overweight or obese men may be postulated to increase the risk of LUTS by enhanced induction of the estrogen receptor and decreased net dihydrotestosterone formation in the prostate. Indeed, higher circulating estradiol concentration has been found to be associated with a higher risk of surgery for benign prostatic hyperplasia (4) and larger prostate volume (13). However, in contrast to this hypothesis, Platz et al. (14) observed an inverse association between serum estradiol levels and benign prostatic hyperplasia in a large sample.
The association of weight gain with LUTS may have reflected that the increase in BMI during adulthood is due largely to an increase in central adiposity and supports the hypothesis of an insulin-mediated effect on LUTS development. Alternatively, Gapstur et al. (11) showed in a prospective study that an increase in BMI during adulthood was associated with declining circulating levels of total and free testosterone as well as sex hormone-binding globulin. This change in the estradiol/testosterone ratio might be associated with maintenance of benign prostatic hyperplasia.
Men who were obese at age 25 years were less likely to have LUTS or noncancer prostate surgery later in life, even after we controlled for current waist circumference. Similarly, in the Health Professionals Follow-up Study (15), men whose BMI at age 21 years was high had a lower risk of prostate cancer later in life. It is likely that these men were also obese during puberty and adolescence, which may have influenced steroid hormone balance during prostate maturation. Obese boys have a delayed onset of puberty (16), likely because of lower testosterone and higher estrogen levels. Berry et al. (17) observed pathologic signs of benign prostatic hyperplasia at ages 3140 years and concluded that the initiation of benign prostatic hyperplasia growth is likely to start before age 30 years. The early phase of development of benign prostatic hyperplasia nodules is thought to be induced by dihydrotestosterone-mediated production of growth-stimulatory factors by the stroma that induce signal transduction within epithelial cells (18). Young obese men with higher estrogen and lower testosterone levels compared with leaner men possibly have lower intraprostatic dihydrotestosterone production. Lower dihydrotestosterone levels might protect against initial development of benign prostatic hyperplasia nodules earlier in adulthood.
No positive associations of current BMI, highest BMI ever, and waist circumference with noncancer prostate surgery were observed. A higher risk of benign prostatic hyperplasia surgery for men with a larger waist circumference was observed in the Health Professionals Follow-up Study (3) but not in another cohort study (4). Daniell et al. (19), who found that obesity was a risk factor for prostate enlargement but not for prostate surgery due to obstructive uropathy in men aged 6074 years, concluded that the risk factors for prostate enlargement and for obstructive uropathy that requires surgical treatment might be different. However, not all men who have an enlarged prostate develop symptoms, and, among those who are symptomatic, not all will choose to have surgery. It might be possible that obese men choose surgery less often than lean men do.
In NHANES III, body weight was assessed retrospectively and cross-sectionally for multiple time points throughout a subjects lifetime, enabling us to consider differences in the influence of adiposity at different stages of life on LUTS and noncancer prostate surgery. We used self-reported current weight and height to be consistent with self-reported weight at age 25 years and highest weight ever. Self-reported current weight and height correlated very highly with current weight and height measured during the physical examination, indicating no serious under- or overreporting of weight or height in this group of men. We found no association between BMI and LUTS after adjustment for age and race. Further adjustment for current waist circumference revealed a stronger inverse association between measured current BMI and LUTS compared with use of self-reported BMI. We cannot completely rule out the possibility that obese people might have underestimated their previous weight, but misreport of past weight is unlikely to be differential with respect to LUTS. We assessed BMI and waist circumference concurrently with LUTS and after noncancer prostate surgery. Therefore, results reflect associations and do not necessarily reflect causal effects. We evaluated the body habitus hypothesis in a sample representative of the US population of older men, aiding in the broad generalizability of these results. In addition, the elderly were oversampled, allowing for stable estimates in our analysis. During the NHANES III interview, participants reported on four of the seven symptoms of the American Urological Association symptom index (6). To preclude a high false-positive rate, we included in our analysis only those men with at least three of the four symptoms, who are more likely to have LUTS than are men with only one or two symptoms. Finally, these results pertain to a selected array of urinary symptoms in men who do not have such symptoms because of factors such as paralysis or being bedridden.
In conclusion, our results suggest that being overweight in young adulthood may be associated with a lower prevalence of LUTS later in life. Weight gain and central adiposity in adulthood are possibly associated with a higher prevalence of LUTS. To directly investigate the findings from our study, we are currently examining the association of glucose and insulin metabolism with LUTS, which might mediate the effect of central adiposity on LUTS. Obesity is an increasing health problem in the United States and other Western countries. If an association between weight gain associated with central adiposity and LUTS exists, it would have an impact on the health of millions of men, affecting their daily life. The advice to avoid weight gain during adulthood could possibly be part of preventive strategies for this common set of urinary symptoms in the general population of noninstitutionalized older men.
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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