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American Journal of Epidemiology Advance Access originally published online on February 7, 2008
American Journal of Epidemiology 2008 167(8):925-934; doi:10.1093/aje/kwm389
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Dietary Patterns, Supplement Use, and the Risk of Symptomatic Benign Prostatic Hyperplasia: Results from the Prostate Cancer Prevention Trial

Alan R. Kristal1,2, Kathryn B. Arnold1, Jeannette M. Schenk1,2, Marian L. Neuhouser1, Phyllis Goodman1, David F. Penson3 and Ian M. Thompson4

1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA
2 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA
3 Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA
4 Department of Urology, University of Texas Health Sciences Center, San Antonio, TX

Correspondence to Dr. Alan R. Kristal, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: akristal{at}fhcrc.org).

Received for publication July 6, 2007. Accepted for publication December 11, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
This study examined dietary risk factors for incident benign prostatic hyperplasia (BPH) in 4,770 Prostate Cancer Prevention Trial (1994–2003) placebo-arm participants who were free of BPH at baseline. BPH was assessed over 7 years and was defined as medical or surgical treatment or repeated elevation (>14) on the International Prostate Symptom Score questionnaire. Diet, alcohol, and supplement use were assessed by use of a food frequency questionnaire. There were 876 incident BPH cases (33.6/1,000 person-years). The hazard ratios for the contrasts of the highest to lowest quintiles increased 31% for total fat and 27% for polyunsaturated fat and decreased 15% for protein (all ptrend < 0.05). The risk was significantly lower in high consumers of alcoholic beverages (0 vs. ≥2/day: hazard ratio (HR) = 0.67) and vegetables (<1 vs. ≥4/day: HR = 0.68) and higher in daily (vs. <1/week) consumers of red meat (HR = 1.38). There were no associations of supplemental antioxidants with risk, and there was weak evidence for associations of lycopene, zinc, and supplemental vitamin D with reduced risk. A diet low in fat and red meat and high in protein and vegetables, as well as regular alcohol consumption, may reduce the risk of symptomatic BPH.

alcohol drinking; diet; dietary supplements; prostatic hyperplasia

Abbreviations: BPH, benign prostatic hyperplasia; CI, confidence interval; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FFQ, food frequency questionnaire; HR, hazard ratio; IPSS, International Prostate Symptom Score; PCPT, Prostate Cancer Prevention Trial


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Benign prostatic hyperplasia (BPH) is one of the most common medical conditions in older men. Estimates of BPH prevalence range from 40 percent to 50 percent at 50 years of age to as high as 80 percent for men aged 70 years (1, 2). Both the high prevalence of BPH and the associated costs of medical care (approximately 4 billion dollars per year in the United States) strongly motivate research to better understand the causes of BPH and identify modifiable risk factors to prevent or delay the disease (3). The current literature on BPH risk factors is quite limited. Most reports have been based on case series, cross-sectional associations, or hospital-based case-control studies, and few studies have examined the risk of incident BPH using case definitions that reflect current medical practice and validated symptom questionnaires. The only well-established modifiable risk factor for BPH is obesity and, in particular, abdominal obesity (4–7). Of the studies examining diet, only two have examined dietary risk factors for incident BPH (8, 9). Large studies of diet and BPH incidence are needed to clarify how diet may affect BPH risk.

Symptomatic BPH is caused by two components: enlargement of the prostate and heightened tone in prostate smooth muscle, both of which can obstruct urinary flow. Although the pathogenesis of BPH is not well understood, age-related changes in hormonal and other growth-regulatory factors are the likely cause of cellular proliferation (10). Thus, dietary patterns that alter the hormonal milieu, such as a high-fat diet, or other regulator factors, such as insulin-like growth factors, could conceivably affect BPH risk. Prostate smooth muscle tone is controlled by the sympathetic nervous system, which is directly affected by many diet-related factors including energy intake, hyper- and hypoglycemia, and obesity (11, 12). BPH may also be caused or exacerbated by chronic inflammation and subsequent oxidative damage (13), and thus dietary factors such as {omega}-3 fatty acids, polyunsaturated fats, and antioxidants may also affect risk. Clearly, there are many mechanisms whereby dietary patterns could affect the risk of symptomatic BPH.

Here, we give results of a prospective cohort study examining the 7-year incidence of symptomatic BPH among men participating in the Prostate Cancer Prevention Trial (PCPT). Data from the PCPT include rigorous assessment of both the symptoms and treatment of BPH, as well as extensive information on diet and other lifestyle factors that may affect BPH risk. This report examines whether dietary patterns, supplement use, and alcohol consumption affect the risk of incident, symptomatic BPH in a population of healthy men aged 55 years or older.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Data are from placebo arm participants in the PCPT, a randomized, placebo-controlled trial testing whether finasteride, a 5{alpha}-reductase inhibitor, could reduce the 7-year period prevalence of prostate cancer. Details regarding study design and participant characteristics have been described previously (14). Briefly, 18,880 men aged 55 years or older with normal digital rectal examinations and prostate-specific antigen levels of 3 ng/ml or below, as well as no history of prostate cancer, severe BPH (defined as an International Prostate Symptom Score (IPSS) of 19 or lower), or clinically significant coexisting conditions (judged by the clinic physician to affect survival until or eligibility for the end-of-study biopsy at 7 years postrandomization), were randomized to receive finasteride (5 mg/day) or placebo. During the PCPT, a prostate biopsy was recommended for participants with an abnormal digital rectal examination or a prostate-specific antigen level of 4.0 ng/ml or greater; all men were requested to undergo biopsy at 7 years postrandomization.

Data collection
Extensive data are available on the demographic and lifestyle characteristics of PCPT participants. Details regarding age, race/ethnicity, education, and history of smoking were collected at baseline by self-administered questionnaires. The level of physical activity was assessed by use of a six-item questionnaire and categorized as "sedentary," "light," "moderate," and "very active" (15). Height and weight were measured at the baseline clinic visit.

At 1 year postrandomization, men completed a 15-page diet and supplement questionnaire, and clinic staff measured height, weight, and body circumferences as part of an ancillary study protocol. Diet was assessed with a food frequency questionnaire (FFQ) developed specifically for this population of older men. This FFQ consisted of questions on the usual consumption over the past year of 99 foods or food groups and nine beverages, along with 13 questions on food preparation and purchasing and three questions on usual consumption of fruits, vegetables, and fried foods. Algorithms for analysis of this questionnaire are available at http://www.fhcrc.org/science/shared_resources/nutrition/ffq/tech_doc.pdf. The dietary supplement questionnaire and its analysis have been described in detail previously (16). In brief, participants reported usual pills per day for multivitamins and antioxidant mixtures and both pills per day and dose for β-carotene, vitamin C, vitamin E, calcium, and zinc. In addition, participants reported whether they used stress-type multivitamins, vitamin D, fish oil, B-complex, iron, vitamin A, selenium, or niacin at least three times a week. We conducted an inter- and intramethod reliability study in 150 randomly selected men, to compare nutrients calculated from the initial FFQ, from six 24-hour recalls collected over the following year and from an additional FFQ completed after all 24-hour recalls had been collected. Based on the 128 men who completed at least five 24-hour recalls, correlations between the first FFQ and 24-hour recalls (adjusted for energy and deattenuated for measurement error in the 24-hour recalls) were as follows: total fat, 0.71; polyunsaturated fat, 0.66; monounsaturated fat, 0.66; saturated fat, 0.75; alcohol, 0.84; carbohydrate, 0.70; lycopene, 0.58; β-carotene, 0.58; vitamin D, 0.57; docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA), 0.87; vitamin C, 0.62; calcium, 0.62; vitamin C, 0.40; and zinc, 0.87. Correlations between repeat FFQs were above 0.60 for all nutrients with the exception of 0.54 for EPA plus DHA.

Extensive medical data, including physician diagnosis of and treatment for BPH, prostatitis, diabetes, cardiovascular disease, and cancer, were collected at the baseline clinic visit, each annual and 6-month clinic visit, and every 3- and 9-month phone contact between scheduled clinic visits. At recruitment, randomization, and each annual follow-up clinic visit, participants completed the seven-item IPSS self-administered questionnaire (17).

Incident BPH was defined as either the first report of treatment or the second report of an IPSS of 15 or higher. Treatments included use of {alpha}-blockers, finasteride, or any surgical intervention (transurethral prostatectomy, balloon dilation, or laser prostatectomy). Men who reported a physician diagnosis of BPH alone, in the absence of symptoms or treatment, were not included as cases in this analysis. We did complete analyses that included men reporting a physician diagnosis only as BPH cases and report the few differences in the Results section below.

Statistical methods
All analyses were based on the time between randomization and the estimated time of incident BPH. For cases defined by the IPSS, we assigned incidence time as the midpoint between the second elevated IPSS and preceding IPSS (most often the previous year). For cases defined by treatment, which was assessed every 3 months, we assigned incidence time as the midpoint between the two annual visits when BPH treatment was first reported. Follow-up was censored at the last reported IPSS or at the time of prostate cancer diagnosis. We calculated simple incidence rates as the annual incidence per 1,000 person-years of observation. We used Cox proportional hazards models to calculate the associations of diet with the relative hazards of BPH; p < 0.05 was considered statistically significant, and p values are reported in the text rounded to the third decimal place.

This study is based on 9,457 placebo arm participants, from whom we excluded 33.8 percent with a history of BPH at baseline (542 for surgery, 12 for medication use, 1,090 for an IPSS of 15 or higher at either the recruitment or randomization visit, and 1,548 who reported a previous BPH diagnosis). We excluded an additional 502 men who were missing at least half of the expected number of postrandomization IPSS values, leaving 5,763 participants. We then excluded 993 men with missing data (404 missing food frequency questionnaires, 281 with unreliable dietary data (energy <800 or >5,000 kcal), and 308 missing complete anthropometry data), leaving 4,770 men for analyses. Most men missing diet and anthropometry measures were enrolled at study sites that chose not to participate in the special dietary and anthropometry assessment protocols.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
There were 876 incident BPH cases during the 7 years of follow-up, corresponding to an incidence rate of 33.6 per 1,000 person-years. Most BPH endpoints were based on medical treatment (52 percent) or elevated IPSS (41 percent), and only 7 percent were based on surgery. Table 1 gives distributions of participants' baseline demographic and health-related characteristics, as well as the unadjusted incidence rates for BPH stratified by these characteristics. The mean age of participants was 62.6 (standard deviation: 5.5) years and ranged from 54 years to 86 years. Only 24 percent of men were normal weight (body mass index: <25 kg/m2), and 21 percent had a waist/hip ratio of 1.0 or greater. BPH incidence rates increased with increasing age, body mass index, and waist/hip ratio, and they were higher in African Americans and Hispanics compared with Caucasians.


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  		TABLE 1. Demographic and health-related characteristics of the study sample and their associations with the incidence of symptomatic benign prostatic hyperplasia, Prostate Cancer Prevention Trial placebo arm, 1994–2003

 
Table 2 gives the adjusted hazard ratios for BPH associated with energy and macronutrient intake. There was no association of energy intake with BPH risk. For each macronutrient, we give results from two statistical models, labeled "percent energy" and "total energy." Percent energy models examine the percentage of energy from each macronutrient (for alcohol, models used categorized drinks per day), use a linear term for total energy as a covariate, and can be interpreted as the effect of substituting energy from each specific macronutrient for other macronutrients. Total energy models examine energy from each macronutrient (for alcohol, models used categorized drinks per day), use a linear term for energy from all other macronutrients as a covariate, and can be interpreted as the effect of increasing energy from a specific macronutrient while keeping the energy from each other macronutrient constant. In percent energy models, there were statistically significant increases in BPH risk associated with high percentages of energy from total and polyunsaturated fats and significant decreases in risk associated with a high percentage of energy from protein and number of alcoholic drinks per day (all ptrend < 0.05). Comparing men in the highest and lowest quintiles, risk was 31 percent higher for total fat (p = 0.018), 27 percent higher for polyunsaturated fat (p = 0.025), and 15 percent lower for protein (p = 0.134); compared with less than 1 drink/month, consuming two or more drinks/day was associated with a 33 percent (p < 0.001) reduction in risk. Overall, this pattern of findings was similar in the total energy models. We also fit a model with linear terms for energy from fat, carbohydrate, and protein, plus alcohol categorized by drinks per week, and found significant associations with fat (4.5 percent increase per 100 kcal, p = 0.003), protein (5.1 percent decrease per 100 kcal, p = 0.008), and alcohol (comparing <1/month with ≥2/day: 30 percent reduction, p = 0.002). Finally, we examined whether the finding of increased risk associated with total fat was attributable to saturated, monounsaturated, or polyunsaturated fats specifically. We fit a set of percent energy models that controlled for total fat and a single total energy model that included energy from each type of fat; however, in all of these models, there were no significant associations of any specific type of fat with risk (data not shown).


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  		TABLE 2. Association of energy and macronutrient intake with risk of total incident symptomatic benign prostatic hyperplasia, Prostate Cancer Prevention Trial placebo arm, 1994–2003

 
Table 3 gives associations of micronutrients with BPH risk. We give results for nutrients for which we hypothesized an association with BPH risk because of antioxidant, antiinflammatory, or growth-regulatory properties. We report results for diet alone and for "total" (diet plus supplements) where appropriate. Results for dietary vitamin E and selenium are not reported because, on the basis of very poor correlations between FFQ-based dietary intake of these nutrients and serum concentrations (18–23), we believe they cannot be assessed using an FFQ. Both dietary and total zinc were associated with reduced BPH risk. Compared with men in the lowest quintile of total zinc intake, those in the highest quintile had a 32 percent (p = 0.002) lower BPH risk. Total but not dietary vitamin D was associated with reduced risk. Compared with men in the lowest quintile of total vitamin D intake, those in the highest quintile had an 18 percent reduced BPH risk (ptrend = 0.032). There was a suggestive but not statistically significant 18 percent reduction in BPH risk associated with high lycopene intake (ptrend = 0.056). This association was modestly stronger when physician diagnosis of BPH was included as an endpoint (quintile 1 vs. quintile 5: hazard ratio (HR) = 0.79, 95 percent confidence interval (CI): 0.63, 0.98; ptrend = 0.023). Neither vitamin C, calcium, nonlycopene carotenoids, nor long-chain {omega}-3 fatty acids were associated with risk.


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  		TABLE 3. Association of energy and micronutrient intake with risk of total incident symptomatic benign prostatic hyperplasia, Prostate Cancer Prevention Trial placebo arm, 1994–2003

 
Table 4 gives associations of dietary supplement use with BPH risk. Supplement use is categorized as low, corresponding to no or infrequent use of a supplement, medium, corresponding to the amounts generally obtained from multivitamins, and high, corresponding to amounts that are generally only possible from using high-dose single supplements. The exceptions were EPA plus DHA and single vitamin D supplements, for which we had data only on whether they were used at least three times per week. Thus, EPA plus DHA was coded as 0 or 0.5 g/day, and vitamin D from a single supplement was coded as 0 or 10 µg/day. Because the vitamin D content of multivitamins is also 10 µg, only men who used both multivitamins and single vitamin D supplements could be in the high-dose vitamin D category. There were no associations of supplement use with BPH risk, with the exception of a trend for decreasing BPH risk with increasing dose of supplemental vitamin D (ptrend = 0.048). We also examined results excluding multivitamin users, because regular multivitamin users have, by definition, at least moderate intakes of many micronutrients. In these analyses (not shown), there were no associations of any supplement with BPH risk. In particular, the hazard ratio contrasting users with nonusers of vitamin D supplements was 1.00 (95 percent CI: 0.65, 1.52).


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  		TABLE 4. Association of dietary supplement use with the risk of total incident symptomatic benign prostatic hyperplasia, Prostate Cancer Prevention Trial placebo arm, 1994–2003    

 
Table 5 gives associations of food groups often associated with prostate health. Compared with men eating red meat less than once per week, men eating red meat at least daily had a 38 percent increased BPH risk (p = 0.044) and, compared with men eating fewer than one serving of vegetables per day, men eating four or more servings had a 32 percent decreased BPH risk (p = 0.011). There were no clear dose-response effects for either red meat or vegetables; however, the largest associations were in the contrasts between extreme quintiles. In analyses adding physician-diagnosed BPH as an endpoint, the association with red mean was attenuated and no longer statistically significant (<1 vs. ≥4 servings/day: HR = 1.30, 95 percent CI: 0.97, 1.75), while there was a significant dose response for vegetables with reduced risk (ptrend = 0.023). Neither cruciferous vegetables, fruit, nor dairy products were associated with BPH risk.


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  		TABLE 5. Association of food use with the risk of incident symptomatic benign prostatic hyperplasia, Prostate Cancer Prevention Trial placebo arm, 1994–2003

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
In this large prospective study, we found that diets high in total fat were associated with increased risk of symptomatic BPH and that diets high in protein and alcohol were associated with decreased risk. In analyses of foods, high vegetable consumption was associated with lower risk, and high red meat consumption was associated with increased risk. There were no associations of antioxidant nutrients, including supplemental vitamin E and selenium or total vitamin C, with risk. Dietary but not supplemental zinc was associated with reduced risk, and use of vitamin D supplements was associated with reduced risk. Finally, there was a suggestion that high intake of lycopene, but not other carotenoids, was associated with reduced risk.

Before discussing the consistency of our findings with those in the published literature, it is important to note that research on dietary patterns and BPH is very limited. Most reports are from small case-control studies in which cases were men undergoing surgical treatment (24–27) or from cross-sectional studies examining associations of lower urinary tract symptoms with current diet (28, 29) or serum micronutrient concentrations (30). Two studies used a longitudinal design to examine true BPH incidence, using either surgery (8) or the combination of medical and surgical treatment plus the development of severe lower urinary tract symptoms (9) as BPH endpoints. For dietary assessment, two studies used a FFQ (9, 25, 31), one used serum micronutrients (30), and the rest collected limited information on specific foods or food groups. Given these differences in study design, BPH endpoints, and dietary assessment methods, inconsistencies in findings across studies are expected.

Our finding that total fat was associated with increased BPH risk, with no evidence that associations were specific to type of fat, was in part consistent with the two previous studies that have examined macronutrients and BPH risk. The large study by Suzuki et al. (31) reported modest increases in the 6-year period prevalence of BPH associated with high intakes of energy, animal protein, polyunsaturated fat, and long-chain {omega}-3 fatty acids. Lagiou et al. (25), in a very small case-control study, reported a nonsignificant increased risk associated with high intake of polyunsaturated fat. Our finding that regular alcohol consumption was associated with reduced risk was consistent with findings from many studies that have examined this question (8, 26, 29, 32, 33) and probably due to the effects of alcohol on the production and metabolism of testosterone (34). We did examine whether the alcohol finding could be attributed to avoiding beverages to reduce symptoms; however, BPH incidence was not associated with consumption of either tea or coffee. We did not confirm the previous finding of an increased risk associated with long-chain {omega}-3 fatty acids, and our finding of a decreased risk associated with high protein intake is novel and requires replication.

Both our study and previously published studies do not support an association of antioxidant nutrients with BPH risk. In the only other longitudinal study, Rohrmann et al. (9) reported decreased risks for 8-year BPH period prevalence associated with high intakes of vitamin C from foods (but not supplements) and individual carotenoids (but not lycopene and β-carotene) and no associations with tocopherols. They also found no significant associations of antioxidants with BPH incidence. Lagiou et al. (25) reported no significant associations with antioxidants, although there were nonsignificant reduced risks associated with high intakes of vitamins C and E. Rohrmann et al. (30) reported no significant cross-sectional associations of serum antioxidants with lower urinary tract symptoms, although men in the lowest quintiles of {alpha}-tocopherol, lycopene, and selenium were approximately twice as likely to report symptoms as were men with higher serum antioxidant levels. We judge it unlikely that dietary antioxidants play an important role in preventing symptomatic BPH.

Results from previous studies of specific foods and food groups are generally consistent with our finding that diets high in vegetables are associated with lower BPH risk. The largest studies reported an 11 percent reduction in BPH prevalence when comparing the lowest and highest quintiles of vegetable intake (9) and a 30 percent reduced risk of symptoms when comparing less than daily with daily consumption of fresh vegetables (28). There is also some support of our finding that high intake of red meat increases risk (28, 31).

Our findings on dietary zinc and supplemental vitamin D are difficult to interpret. The correlation between dietary zinc and protein, controlled for energy, was 0.52; in models that included dietary zinc and protein, both associations were attenuated and not statistically significant and, in models that included total zinc and protein, only protein was significant (p = 0.017). Combined with the observation that supplemental zinc was not associated with risk, it is possible that the dietary zinc finding is the result of collinearity with protein. It is also possible that there is a threshold above which zinc has no additional effect on risk. In analyses cross-classifying men by dietary and supplemental zinc intake using quintile 1 of dietary zinc without supplements as the comparison group, the hazard ratios were 0.69 (95 percent CI: 0.52, 0.91) for quintile 1 with supplements, 0.60 (95 percent CI: 0.48, 0.77) for quintiles 2–5 without supplements, and 0.61 (95 percent CI: 0.48, 0.78) for quintiles 2–5 with supplements. Vitamin D supplementation was associated with reduced risk, but our calculated dose of total vitamin D is imprecise, and the association was observed only among men who used both multivitamins and single vitamin D supplements. Larger studies with more detailed data on supplement use, including frequency, dose, and duration, will be needed to further address whether high-dose vitamin D supplementation is associated with BPH risk.

Many of the dietary factors that we found to be associated with BPH risk can affect both steroid hormone concentrations and the sympathetic nervous system. The dietary pattern characterized by low fat, moderate alcohol, and high vegetables is associated with less obesity (15), lower serum estrogens and androgens, and higher sex hormone binding globulin (34, 35) and probably also less sympathetic nervous stimulation (36). It is possible that these physiologic effects moderate both the hormonally regulated prostate growth and heightened smooth muscle tone that cause BPH. Planned future analyses, based on assays of serum steroid hormone, cytokine, and adipokine concentrations, may provide insight into whether these mechanisms underlie associations of diet with BPH risk.

There are several strengths to this study, including the longitudinal design, the large sample size, the standardized and frequent assessments of BPH treatment and symptoms, and the use of incident rather than prevalent BPH as a study endpoint. There are also several limitations. First, all information used to define BPH endpoints was based on self-report, including medical and surgical treatment and lower urinary tract symptoms. We used specific interviewer-administered probes to collect treatment information every 3 months during the duration of the trial, but we did not have access to medical records to validate responses. We also used a standardized and well-validated, self-administered questionnaire to collect symptom data annually, but reporting of symptoms is highly subjective and may differ across racial, ethnic, and socioeconomic groups. Second, we used data from a FFQ to assess diet. Although we did not analyze nutrients that are very poorly ascertained by FFQ, we and many others are concerned by recent studies suggesting that FFQs correlated poorly with unbiased biomarkers of diet and perform poorly compared with dietary records (37). Finally, our assessment of supplement use was incomplete, and in particular we lacked frequency and dose information for selenium, vitamin D, and fish oil.

In conclusion, we found evidence that a dietary pattern high in vegetables and protein, moderate in alcohol, and low in fat and red meat may protect men from developing symptomatic BPH. We found no evidence that antioxidant nutrients, from either supplements or food, were associated with reduced BPH risk, nor did we find evidence that consumption of long-chain {omega}-3 fatty acids, zinc, or calcium was associated with reduced risk. Although confirmatory studies are needed, it is possible that dietary modification could be useful for preventing BPH and the management of BPH symptoms.


   ACKNOWLEDGMENTS
 
This work was supported by National Institutes of Health grants DK63303, CA37429, CA18964, and CA108964.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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A. R. Kristal, J. M. Schenk, Y. Song, K. B. Arnold, M. L. Neuhouser, P. J. Goodman, D. W. Lin, F. Z. Stanczyk, and I. M. Thompson
Serum Steroid and Sex Hormone-Binding Globulin Concentrations and the Risk of Incident Benign Prostatic Hyperplasia: Results From the Prostate Cancer Prevention Trial
Am. J. Epidemiol., December 15, 2008; 168(12): 1416 - 1424.
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