Download Natural History, Epidemiology, and Evaluation of BPH: AUA 2006

Natural History, Epidemiology, and Evaluation of BPH: AUA 2006 Findings
Claus G. Roehrborn, MD
Introduction
The American Urological Association (AUA) Annual Meeting took place from May 20-25, 2006 in the
Georgia World Congress Center in Atlanta, Georgia. As in years past, the topic of lower urinary tract
symptoms (LUTS) and benign prostatic hyperplasia (BPH) was of significant interest, and of the 1725
abstracts presented, approximately 5% were dedicated to this topic. Poster sessions on basic research,
epidemiology, and natural history of BPH were presented. Other highlights included a poster and podium
session on surgery and new technologies and a podium session on medical and hormonal therapy. In
addition, the Endocrine Forum was dedicated this year to a discussion of LUTS and BPH, and a special
forum was held featuring the baseline results of the Boston Area Community Health (BACH) study, an
exciting new population-based study conducted by the New England Research Institute and supported by
a grant from the National Institutes of Health/National Institute of Diabetes & Digestive & Kidney
Diseases.
Natural History, Epidemiology, and Evaluation
Data from the Integrated Healthcare Information Services, Inc. (IHCIS) National Medicare Benchmark
Database, which includes information on more than 30 managed care plans and covers 25 million lives,
were analyzed by Naslund and colleagues.[1] Among 1,134,491 male patients over the age of 50 with a
total of 963,425 years of follow-up, they found that BPH is the fourth most common treated disease with a
prevalence rate of 13.5%, following coronary artery disease and hyperlipidemia, hypertension, and type 2
diabetes mellitus. Incidentally, prostate cancer at a 7.8% prevalence rate ranks number 10 in this
population. The authors also analyzed the costs associated with the treatment for these 10 most common
conditions and found that prostate cancer and BPH were among the 10 most costly diseases to treat,
according to this database, with prostate cancer being first and BPH eighth on the list. This finding
highlights the enormous socio-economic importance of prostate diseases, both benign and malignant, to
our society and healthcare delivery system.
A topic that has generated great interest recently is the association of male pelvic diseases such as LUTS
and BPH, as well as erectile dysfunction, with the metabolic syndrome. Parsons and coworkers [2]
examined metabolic factors associated with BPH using data on 422 adult men who had undergone
magnetic resonance imaging of the prostate as part of the Baltimore Longitudinal Study of Aging. The
study authors attempted to determine whether body mass index (BMI), fasting glucose, and diabetes
mellitus were associated with prostate enlargement and AUA Symptom Score, adjusting for age and
serum testosterone level. The authors defined prostate enlargement as a prostate volume of greater than
40 cc at the first visit. They found that the odds ratio (OR) for having an enlarged prostate was
significantly greater in men with a BMI of greater than 35 (OR = 3.52), but also for those with a fasting
glucose of greater than 110 (OR = 2.98) compared with those with a fasting glucose of less than 110.
They conclude that obesity, elevated fasting plasma glucose, and diabetes mellitus -- in short, those
factors contributing to the metabolic syndrome -- are all risk factors for BPH. This adds further information
to our already existing knowledge base regarding the relationship between the metabolic syndrome and
BPH.[3,4]
Roehrborn and colleagues[5] analyzed baseline data from 5 BPH trials and 1 prostate cancer prevention
trial (REDUCE ), involving over 19,000 men in all, to determine whether there is a relationship between
alcohol consumption and measures of LUTS and BPH as well as to study explanatory variables for sexual
dysfunction in this group of men. The participants were classified into 4 groups stratified by units of
alcohol consumption per week ranging from "never drink any alcohol" to "drinking more than six units per
week." Surprisingly, there were no differences with regard to age or BMI among the 4 groups. Prostate
size was slightly smaller in those with regular alcohol consumption than in those who never drink alcohol,
serum prostate-specific antigen (PSA) was slightly higher in those with regular alcohol consumption, and
PSA density ranged from 10.1 ng/mL in those who never consume alcohol to 11.5 ng/mL in those who
consume more than 6 units per week. Dihydrotestosterone (DHT) and testosterone levels, however, were
not significantly different among the groups studied. LUTS severity was significantly worse on all
measures in those claiming never to drink any alcohol compared with those who drank occasionally or
regularly. This was true for the total symptom score, the irritative and obstructive score, as well as for the
maximum urinary flow rate (Figure 1). Men who never drink any alcohol were significantly less likely to be
sexually active compared with those who admitted to the consumption of alcohol either occasionally or
regularly (OR 1.406).
Figure 1. Relationship between alcohol consumption and mean total IPSS.
In a second analysis using data from the same collection, Roehrborn and coworkers [6] tried to determine
whether age, BMI, and International Prostate Symptoms Score (IPSS) were associated with sexual
activity, erectile dysfunction, decreased libido, and sexual dysfunctions as assessed by the Problem
Assessment Scale of the Sexual Function Inventory (PAS SFI). Age, BMI, and LUTS symptom severity as
measured by the IPSS were significantly related to all 4 measures of sexual function. In general, elderly
men and men with high BMI had a deterioration of their sexual function. While this finding is certainly
expected, the surprising finding was that sexual inactivity, decreased libido, and erectile dysfunction all
increased in prevalence with increasing IPSS, while the PAS SFI score decreased dramatically in the
same direction. These findings corroborate several cross-sectional, population-based studies, which also
found a strong correlation between LUTS severity and measures of erectile function.[7] Additional data
supporting this relationship are expected from the BACH study. While not implying a causal link, it
appears quite clear that both conditions may result from a common pathophysiologic background, and
further basic research is needed to better understand these mechanisms, perhaps involving the nitric
oxide synthase/nitric oxide system, pelvic ischemia, or even inflammatory conditions in the male pelvis.
The pharmaceutical company, sanofi-aventis, is currently supporting a BPH registry and patient survey
which has enrolled over 6900 men at 402 sites across the United States. The objective of this BPH
registry is to examine patient management practices of primary care providers and urologists, and to
assess patient outcomes, including symptom amelioration and disease progression, in a real-world
setting. At this year's AUA meeting, several abstracts were presented from the baseline data of the
registry.[8-10] One of the original research questions was the difference between the management styles of
primary care physicians and urologists. It was found that not only were there significant differences
between specialists and nonspecialists regarding the evaluation of men with LUTS and BPH, but also
regarding the use of medication. Urologists were far more likely to use combination therapy and 5alphareductase inhibitors, and less likely to use non-selective alpha blockers, compared with the primary care
providers (Figure 2).
Figure 2. Difference between prescribing patterns of urologists and primary care
providers in the treatment of LUTS/BPH.
The issue of ejaculatory disorders and their correlation with LUTS severity in men with BPH was also
examined by Rosen and Fitzpatrick.[11] In this study, 2442 sexually active men in Europe were asked to
complete the IPSS questionnaire and Male Sexual Health Questionnaire (MSHQ). Men with more severe
LUTS symptomatology experienced worse ejaculatory function than those with mild or moderate
symptoms (Table 1). It is perhaps unexpected to see such an extraordinarily high prevalence of reduced
ability to ejaculate, delayed ejaculation, decreased force of ejaculation, and decreased amounts of semen
as well as general bother associated with ejaculation. Particularly surprising is the fact that, overall,
25.9% of men claimed to experience pain and discomfort during ejaculation, a number that increased
from 15.4% for those with mild LUTS to 43.2% for those with severe LUTS.
Table 1. Correlation of Ejaculatory Disorders With LUTS Severity in Men With BPH
IPSS IPSS IPSS
< 8 8-19 20-35
Reduced ability to ejaculate (%)
43.3
56.7
67.3
Delayed ejaculation (%)
39.4
52.4
62.9
Decreased force of ejaculate (%)
61.9
76.4
80.9
Decreased amount of semen (%)
59.3
70.9
74.1
Pain/discomfort during ejaculation (%) 15.4
25.8
43.2
Bother associated with ejaculation (%) 37.9
48.6
59.9
Frequency-volume charts (FVC) or voiding diaries have been far more commonly used in Europe than in
the United States. It seems logical to ask patients to fill out information about the frequency of their
urination as well as the expelled urine volume over a period of 48 to 72 hours prior to their visit with a
healthcare provider, as such data form an excellent basis for the discussion of drinking habits and fluid
intake vs volume output, and these data provide objective information regarding actual frequency and
nocturia. Why American healthcare providers have been reluctant to embrace this as a standard
assessment tool is unclear. However, 3 groups reported their findings with FVC in the section on
epidemiology and evaluation of LUTS and BPH.
Anneveld and colleagues[12] demonstrated that the FVC has discriminatory value in analyzing micturition
disorders and recommended its use as a first-time diagnostic test in evaluating men with LUTS and BPH.
Yap and coworkers[13] studied the relationship between FVCs and IPSS and found no simple relationship
between these data. There was no strong association between the self-rated IPSS measure of urinary
symptoms and the measures of voiding behavior based on objective data. The authors suggested that
this is somewhat unexpected given the fact that several questions of the IPSS questionnaire are similar to
the variables assessed in an FVC. For example, the IPSS questionnaire asks specifically about frequency
of urination and nocturia, clearly information that is gathered in an FVC. This is not an entirely new
finding, as other authors have reported that the patients' perception of frequency and nocturia as reported
on the IPSS questionnaire does not necessarily match the actual frequency of urination nor the episodes
of nightly urination. Kaplan and colleagues[14] suggested that the FVC is actually a better measure than
IPSS of improvement of LUTS symptoms in men treated with medications for LUTS and BPH. In a
treatment trial with an alpha blocker, the IPSS improved by 25.7% and the maximum flow rate by 15%;
however, urinary frequency and nocturia on an FVC improved by 33.7% and 33%, respectively, a
significantly greater margin of improvement. All of these observations together suggest that healthcare
providers engaging in the counseling and treatment of men with LUTS and BPH should take more
frequent advantage of this tool in their practice.
References
1. Naslund MJ, Issa MM, Fenter TC. The prevalence, costs, and burden of enlarged prostate (EP) in
men =50 years of age. Program and abstracts of the American Urological Association 2006
Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1345.
2. Parsons JK, Ballentine Carter H, Partin AW, et al. Metabolic factors associated with benign
prostatic hyperplasia: the Baltimore Longitudinal Study of Aging. Program and abstracts of the
American Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia.
Abstract 1344.
3. Hammarsten J, Hogstedt B. Hyperinsulinaemia as a risk factor for developing benign prostatic
hyperplasia. Eur Urol. 2001;39:151-158. Abstract
4. Rohrmann S, De Marzo AM, Smit E, Giovannucci E, Platz EA. Serum C-reactive protein
concentration and lower urinary tract symptoms in older men in the Third National Health and
Nutrition Examination Survey (NHANES III). Prostate. 2005;62:27-33. Abstract
5. Roehrborn CG, Marberger M, Wolford E, et al. Relationships between alcohol use and measures
of LUTS/BPH severity: baseline data from dutasteride studies involving a total of 18,914 subjects.
Program and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25,
2006; Atlanta, Georgia. Abstract 1350.
6. Roehrborn C, Marberger M, Wolford E, Wilson T. Explanatory variables for measures of sexual
dysfunction in LUTS/BPH and prostate cancer risk reduction studies: baseline data from
dutasteride studies involving a total of 18,914 subjects. Program and abstracts of the American
Urological Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1348.
7. Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual dysfunction:
the multinational survey of the aging male (MSAM-7). Eur Urol. 2003;44:637-649. Abstract
8. Steers WD, Nuckolls J, Seftel AD, et al. Differences between PCPs and urologists in the
evaluation of men with LUTS/BPH. Program and abstracts of the American Urological
Association 2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 6.
9. Wei JT, Nuckolls J, Miner M, et al. Differences in medical management of LUTS/BPH between
PCPs and urologists. Program and abstracts of the American Urological Association 2006 Annual
Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 7.
10. Rosen RC, Marks L, McVary K, Roehrborn C, O'Leary M, Lue T. Association between ejaculatory
dysfunction and therapy among men enrolled in the BPH registry & patient survey. Program and
abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006;
Atlanta, Georgia. Abstract 921.
11. Rosen RC, Fitzpatrick J. All components of ejaculation are impaired in men with LUTS suggestive
of BPH. Program and abstracts of the American Urological Association 2006 Annual Meeting;
May 20-25, 2006; Atlanta, Georgia. Abstract 1360.
12. Anneveld M, van Haarst E, Heldeweg E. A comparison of frequency-volume-charts in men with
and without voiding complaints. Program and abstracts of the American Urological Association
2006 Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1351.
13. Yap TL, Cromwell D, Van der Meulen J, Emberton M. The relationship between frequencyvolume chart data and the International Prostate Symptom Score (IPSS) in men with lower
urinary tract symptoms. Program and abstracts of the American Urological Association 2006
Annual Meeting; May 20-25, 2006; Atlanta, Georgia. Abstract 1355.
14. Kaplan SA, Kaplan J, Gonzalez R, Te A. The use of a voiding diary to evaluate urinary frequency
and nocturia is a better indicator than the IPSS in assessing alpha blocker efficacy in men with
lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Program
and abstracts of the American Urological Association 2006 Annual Meeting; May 20-25, 2006;
Atlanta, Georgia. Abstract 1359.