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 5alpha-reductase 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
< 8 / IPSS
8-19 / IPSS
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 frequency-volume 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.