Male LUTS, OAB, Sex: natural history JR Sathiya
Definitions Newer concepts of LUTs Natural history of BPH Prevalence of LUTs
Definition BPH- represents a histologic diagnosis that refers to the proliferation of smooth muscle and epithelial cells within the prostatic transition zone. BPE- is defined as prostatic enlargement due to histologic benign prostatic hyperplasia. The term prostatic enlargement should be used in the absence of prostatic histology BOO- is the generic term for obstruction during voiding and is characterized by increased detrusor pressure and reduced urine flow rate.
ICS(2002) Definition of LUTS Subjective indicator of a disease or change in condition as perceived by patient, caregiver/partner and may lead him/her to seek help from health care professionals Storage symptoms include increased micturition frequency, nocturia, urinary urgency, and urinary incontinence Voiding symptoms include slow or weak stream, hesitancy, and terminal dribble Postmicturition symptoms include the sensation of incomplete emptying and postmicturition dribble
ICS Definition of OAB Urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathology.
Newer Concepts of LUTs Previously BPH used interchangeably with LUTs. Bladder and prostate as a single functional unit. LUTs- multifactorial LUTs association with chronic disease, metabolic syndrome, sexual dysfunction
Figure 91 1. Diagram showing the relationship between histologic hyperplasia of the prostate (BPH), lower urinary tract symptoms (LUTS), benign prostate enlargement (BPE), and bladder outlet obstruction (BOO). The size of the circles does not represent actual proportions but rather illustrates the partial overlap between the different disease definitions. (From Roehrborn CG. Pathology of benign prostatic hyperplasia. Int J Impot Res 2008;20[Suppl. 3]:S11 8.) Claus G. Roehrborn- Prostatic Hyperplasia: Etiology, Pathophysiology, Epidemiology, and Natural History; Campbell-Walsh Urology 10th Edition
LUTS Storage Voiding Post- Micturition Urgency Frequency Urge Incontinence Nocturia Slow or Intermittent Stream Straining Hesitation Feeling of Incomplete Emptying Post- Micturition Dribble DO BOO Detrusor Underactivity BOO Detrusor Underactivity (Male/Female) OAB (Male) (Female) BPH Undefined (Male) (Female) BOO Undefined Drug Discovery Today: Therapeutic Strategies Figure 1. Lower urinary tract symptoms (LUTS) by type, key symptoms, underlying pathophysiology and relation to disease entity.
Risk factors of BPH/LUTs
Natural History of BPH
Natural history The natural history of a disease process refers to the prognosis of the disease over time. In other words, the measurement of changes in parameters of interest and the incidence rates of significant outcomes constitute what is commonly referred to as the natural history of a disease.
How to elucidate natural history of LUTS? Longitudinal studies of untreated cohorts of men diagnosed with LUTS and clinical BPH by any definition (watchful waiting cohorts). Studies of the behavior of men diagnosed with LUTS and BPH and enrolled in controlled studies of LUTS and BPH (control groups) and receiving: no treatment (compared with active intervention) placebo treatment (compared with medical treatment)eg PLESS, MTOPS sham treatment (compared with device or surgical treatment) Longitudinal studies of unselected (i.e., undiagnosed) men living in the community who are less likely to progress and request or require therapy (longitudinal population-based studies)-olmstead County
Problems with untreated cohorts and controlled groups Ethical issues with regards to following up symptomatic men Contact with healthcare personnel establishes bias Requirement of treatment during follow-up causes dropout from study Inclusion/Exclusion criteria renders the study population unnatural
Longitudinal population based studies Difficult to conduct Expensive Some bias remains when tests are conducted to understand the disease progression (i.e. flow rate, IPSS, prostate volume, etc) Probably the best in understanding natural history of any disease
Vol 155.595-600. February 1996 Prrnfed 111 U.S.A. NATURAL HISTORY OF PROSTATISM: LONGITUDINAL CHANGES IN VOIDING SYMPTOMS IN COMMUNITY DWELLING MEN STEVEN J. JACOBSEN," CYNTHIA J. GIRMAN, HARRY A. GUESS, THOMAS RHODES, JOSEPH E. OESTERLING AND MICHAEL M. LIEBER From th~a Departments of Health Sciences Research (Section of Clinical Epidemiology) and Urology, Mavo Clinic and Mayo Foundatcon, Rorhester, Minnesota, Merck Research Laboratories, Blue Bell, Pennsylvania, and Michigan Prostate Institute and University of Michigan, Ann Arbor, Michigan Olmsted County Study 0022-5347/95/1535-1510$03.00/0 THE JOURNAL OF UROLOGY Copyright 0 1995 by AME~lclw UROLOCICAL ASSOCIATION, INC. VOI. 153, 1510-1515, May 1995 Printed in U.S.A. NATURAL HISTORY OF PROSTATISM: RELATIONSHIP AMONG SYMPTOMS, PROSTATE VOLUME AND PEAK URINARY FLOW RATE CYNTHIA J. GIRMAN, STEVEN J. JACOBSEN, HARRY A. GUESS, JOSEPH E. OESTERLING, CHRISTOPHER G. CHUTE, LAUREL A. PANSER AND MICHAEL M. LIEBER From the Department of Epidemiology, Merck Research Laboratories, West Point, Pennsylvania, Section of Clinical Epidemiology, Health Sciences Research and Department of Urology, Mayo Clinic, Rochester, Minnesota, Departments of Epidemiology and Biostatistics, University of North Carolina, Chapel Hill, North Carolina, and Section of Urology, University of Michigan and The Michigan Prostate Institute, Ann Arbor, Michigan
Olmsted County Study The Olmsted County Study was initiated in 1990 and followed for 12 years a randomly selected cohort of 2115 men aged 40 79 years. It provides the largest body of evidence that BPH is an age-related and progressive disease.
Round 1 Round 2 Round 3 229 replacements 103 replacements 19 dead 33 dead I 95 FIG. 1. Design of Olmsted County Study of Urinary Symptoms and Health Status Among Men. FIG. 2. Movement of baseline cohort across categories of lower urinary tract symptom severity. Round 2o-mild in round 1. Round Ph-moderate to severe in round 1. Round 3c and e-mild in round 2. Round 3d and f-moderate to severe in round 2. Median interval was 18 months between rounds 1 and 2, and 42 months between rounds 1 and 3.
Olmsted County Trial At inclusion, 26% of men aged 40 49 years had moderate to severe LUTS, and this increased to 46% in men aged 70 79 years The median peak flow rate decreased from 21.2 ml/s to 14.2 ml/s in men in the respective age groups.
Olmsted County Study At the follow-up, the severity of LUTS increased and the peak flow rate decreased, with time and age TABLE 1 Changes in IPSS, peak flow rate, prostate size and cumulative incidence of serious outcomes in the Olmsted County study Variable Age, years Overall 40 49 50 59 60 69 70 Number of patients 2115 839 587 434 252 IPSS [5] Baseline, mean 6.3 5.3 6.2 7.3 7.8 Mean (SD) change/year 0.18 (1.22) 0.05 (1.06) 0.18 (1.19) 0.44 (1.35) 0.14 (1.43) Peak flow rate [4] n assessments 466 191 133 93 49 Baseline, median 21.2 21.3 16.3 14.2 Median change/year, % 2.1 1.1 2.7 2.3 6.2 Prostate volume [6] Median growth per year, % 1.9 1.9 1.9 1.8 1.6 Cumulative incidence of AUR events over 4 years, n (%) [7] 57 (2.7) 10 (1.2) 9 (1.5) 16 (3.7) 22 (8.7) Cumulative incidence of surgical procedures over 6 years [8], n (%) TURP 45 (2.1) 1 (0.1) 5 (0.9) 21 (4.8) 18 (7.1) MIST 19 (0.9) 0 6 (1.0) 7 (1.6) 6 (2.4) Total 64 (3.0) 1 (0.1) 11 (1.9) 28 (6.5) 24 (9.5) MIST, minimally invasive surgical therapies.
Olmsted County Study There was a mean increase in the AUASI/IPSS of 0.18 points per year, ranging from 0.05 in men in their forties to 0.44 in men in their sixties. The annual increase in AUASI/IPSS was low (0.14) in men aged 70 79 years, but there was no obvious reason for this. The study also showed a decrease in median peak flow rate of 2.1% per year that was also age-related, with men aged 70 years showing a more rapid decline (6.2% per year) than men in their fifties (1.1% per year).
FIGURE 2. Mean urinary flow rates measured in 2,113 men from Olmsted County, Minnesota, reveal a decrease in rates with increasing age. Adapted with permission from Girman et al. J Urol 150: 887 892, 1993. 11
Olmsted County Study The cumulative incidence of AUR was 2.7% over 4 years, ranging from 1% in men in their fifties to 9% in men aged 70 years. Overall, 3% of men had TURP or a minimally invasive surgical procedure during a 6-year followup, and this was again strongly age-related (from 0.1% in men aged 40 49 years to 9.5% in men aged 70 79 years)
) e l 0.- 10 c "1 -r-- J-r------ A 0 - s 0 0 1 2 3 4 5 6 Time from baseline questionnaire (yr) Plot of cumulative incidence of acute retention by years of followup since com letion of baseline questionnaire. Different lines represent decades orage. Solid line re resents ages 40 to 49, small dashed line ages 50 to 59, medium dasled line ages 60 to 69 and large dashed line ages 70 to 79 years.
Olmsted County Study Prostate growth also increased with time by a median of 1.9% per year. Age had little influence on prostate growth but men with large prostates at baseline had higher median growth rates (2.2% per year for prostates of >30 ml vs 1.7% per year for prostates of 30 ml). Serious outcomes, such as AUR and the need for BPH-related surgery, appeared to be low in this community-based population.
NATURAL HISTORY OF PROSTATISM -- ms % L y s n r r f m u d ~ ysn rllh 8-30 30 = 20 P c w 9 2 10 0 Am40-49 50-59 60-69 70-79 40-49 50-59 60-69 70-79 (a) 96 with peak flow rate 4 10 mlh (b) % with prostate volune > 50 ml -hatched bars represent subjects with mild or no symptoms. Single hatched bars reflect those with mod
Prevalence of Male LUTS and OAB
european urology 50 (2006) 1306 1315 available at www.sciencedirect.com journal homepage: www.europeanurology.com Incontinence EPIC Population-Based Survey of Urinary Incontinence, Overactive Bladder, and Other Lower Urinary Tract Symptoms in Five Countries: Results of the EPIC Study Debra E. Irwin a, *, Ian Milsom b, Steinar Hunskaar c, Kate Reilly d, Zoe Kopp d, Sender Herschorn e, Karin Coyne f, Con Kelleher g, Christian Hampel h, Walter Artibani i, Paul Abrams j Study available at www.sciencedirect.com journal homepage: www.europeanurology.com EUROPEAN UROLOGY 56 (2009) 14 20 Platinum Priority Voiding Dysfunction Editorial by Christopher R. Chapple on pp. 21 23 of this issue Prevalence, Severity, and Symptom Bother of Lower Urinary Tract Symptoms among Men in the EPIC Study: Impact of Overactive Bladder Debra E. Irwin a, *, Ian Milsom b, Zoe Kopp c, Paul Abrams d, Walter Artibani e, Sender Herschorn f
EPIC Study The EPIC study was a population-based, crosssectional telephone survey of 19 165 adults aged >18 yr in five countries All respondents were asked about demographics, the presence of UTI, the presence of individual LUTS using current ICS definitions, and IPSS. IPSS scores were used to assess LUTS severity: 0, none; 1 7, mild; 8 19, moderate; 20 35, severe.
EPIC Study The presence of OAB symptoms was determined by a response of yes to either of the following questions: Do you experience a sudden compelling desire to urinate which is difficult to put off?; and Do you leak urine with a sudden compelling desire to urinate? Respondents who reported UTI were excluded from this cohort
EPIC Study-Results in the General Population Among men in the general population sample (n = 7210), 62.5% reported experiencing one or more LUTS; 37.7% (ie, 60% of all men reporting any LUTS) reported experiencing only one LUTS subtype, whereas 24.8% (ie, 40% of all men reporting any LUTS) reported experiencing one or more LUTS subtype. The most commonly reported clusters of LUTS subtypes were storage plus voiding LUTS 10.8% of men had urgency (hallmark symptom of OAB)
LUTS
all men with OAB symptoms (n = 502) reported urgency; 29.3% reported only storage symptoms. Men with OAB symptoms reported a greater prevalence of multiple LUTS subtypes than men in the general population ( p < 0.05). All three LUTS subtypes were reported by 37.3% of men with OAB symptoms, 21.3% reported voiding plus storage symptoms, and 12.2% reported postmicturition plus storage symptoms OAB
The most common storage symptom was nocturia among men in the general population (48.6%;), which increased with age (p < 0.05)
Nocturia was the second most common storage symptom among men with OAB symptoms (75.3%) after urgency (100%) The prevalence of storage LUTS increased with age ( p < 0.05)
Terminal dribble (general population, 14.2%; OAB cases, 36.9%) and the sensation of incomplete emptying (general population, 13.5%; OAB cases, 36.9%)were the most frequently reported voiding and postmicturition symptoms
Among men with OAB symptoms, prevalence of voiding and postmicturition LUTS were variable with increasing age
Fig. 3 Distribution (%) of number of lower urinary tract symptoms (LUTS) by age group among (a) men in the general population (n = 7210) and (b) men in the overactive bladder (OAB) population (n = 502). The number of individual LUTS reported by each respondent increased with age ( p < 0.05), particularly among men with OAB symptoms The overall prevalence of any LUTS increased with age in the general population, from 51.3% for men <40 yr to 80.7% for men >60 yr ( p < 0.05).
Symptom severity & bother More than 6% of men in the general population reported moderate (5.4%) or severe (0.7%) LUTS, as scored by the IPSS. By contrast, almost 30% of men with OAB symptoms reported moderate (25.5%) or severe (4.4%) LUTS. For both populations, the proportional increase in men reporting any LUTS (mild, moderate, or severe) with age was significant (p<0.05). Overall, mean IPSS was nearly three times higher among men with OAB symptoms versus the general population sample
Sex
Boston Area Community Health (BACH) survey population-based random sample survey on prevalence of LUTS and association with risk factors Association with chronic diseases eg DM, hypertension, heart disease,depression Association with metabolic syndrome Association with erectile dysfunction
Relationship Between Lower Urinary Tract Symptoms and Erectile Dysfunction: Results From the Boston Area Community Health Survey Sara T. Brookes,* Carol L. Link, Jenny L. Donovan and John B. McKinlay From the Department of Social Medicine, University of Bristol, Bristol, United Kingdom and New England Research Institutes (CLL, JBM), Watertown, Massachusetts d severity by age and AUA-SI score. Moderate and severe LUTS were combined due to relatively smal
European Urology European Urology 44 (2003) 637 649 Lower UrinaryTract Symptoms and Male Sexual Dysfunction: The Multinational Survey of the Aging Male (MSAM-7) Raymond Rosen a,*, Jens Altwein b, Peter Boyle c, Roger S. Kirby d, B. Lukacs e, Eric Meuleman f, Michael P. O Leary g, Paolo Puppo h, Chris Robertson c, Francois Giuliano i Sexual activity was reported by 83% of the sample, with 71% reporting at least one episode of sexual activity during the previous 4 weeks. Sexual disorders and their bothersomeness were strongly related to both age and severity of LUTS
Base: Total sample 10 98 8.6 7.6 6.6 7 6 5 4 3 2 1 0 LUTS Severity Age Cohort 0 4.9 Mild Moderate Servere 5.7 5.7 0 4.6 3.7 4.0 3.5 Mild Moderate Servere 0 2.6 1.7 Mild Moderate Servere 50-59 years 60-69 years 70-79 years Fig. 1. Average number of sexual activities, including intercourse, per month. (a) In% 100 90 80 70 60 50 40 30 20 10 0 LUTS Severity Age Cohort 27 45 14 25 12 2 2 5 17 0 Mild Base: Total sample 50 70 53 Moderate Severe 40 33 7 0 Mild 49 43 6 Net reduction of stiffness No, I cannot get an erection 89 83 83 65 53 12 64 19 Moderate Severe 57 41 16 0 Mild 70 50 52 20 31 45 44 Moderate Severe 50-59 years 60-69 years 70-79 years