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The global burden of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A systematic review and meta-analysis

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• Published: 11 August 2017

The global burden of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A systematic review and meta-analysis

• Shaun Wen Huey Lee, 
• Esther Mei Ching Chan & 
• Yin Key Lai 

Scientific Reports volume 7, Article number: 7984 (2017) Cite this article

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Abstract

Benign prostatic hyperplasia is a common non-malignant condition among older men, but the epidemiology is poorly characterised. We summarised and determined the global preval‎ence of benign prostatic hyperplasia. A systematic search on PubMed, EMBASE and CENTRAL was performed up until 31st July 2016. Studies that described the epidemiology of benign prostatic hyperplasia were included and cumulative plots of preval‎ence estimates were calculated. A total of 31 preval‎ence rate estimates from 25 countries were identified. The combined preval‎ence estimates showed that the lifetime preval‎ence of BPH was 26.2% (95% CI: 22.8–29.6%). We found that there was an increasing preval‎ence of BPH with age. However, we found no significant difference between (a) rural, urban or mixed sites, (b) different countries, (c) respondent representativeness. (d) sample size or (e) study quality. We also found no significant change in the preval‎ence over the past 20 years. While there is substantial variation between sites estimates, results suggest that nearly 1 in 4 men will suffer from BPH over their lifetime. The study revealed there are significant gaps in knowledge, which provides opportunities for future research to further enrich the epidemiological landscape with data.

양성 전립선 비대증은 

고령 남성에게 흔히 나타나는 비악성 질환이지만, 

그 역학은 제대로 밝혀지지 않았습니다. 

저희는 양성 전립선 비대증의 전 세계적 유병률을 요약하고 결정했습니다. 2016년 7월 31일까지 PubMed, EMBASE, CENTRAL에 대한 체계적인 검색이 수행되었습니다. 양성 전립선 비대증의 역학을 설명하는 연구가 포함되었고, 유병률 추정치의 누적 플롯이 계산되었습니다. 25개 국가에서 총 31개의 유병률 추정치가 확인되었습니다. 

종합된 유병률 추정치에 따르면, 

BPH의 평생 유병률은 26.2%(95% CI: 22.8–29.6%)였습니다. 

연령이 증가함에 따라 

BPH의 유병률이 증가한다는 사실이 밝혀졌습니다. 

그러나 

(a) 농촌, 도시 또는 혼합 지역, (b) 다른 국가, (c) 응답자 대표성 사이에는 유의미한 차이가 없었습니다. (d) 표본 크기 또는 (e) 연구의 질. 또한 지난 20년 동안 유병률에 큰 변화가 없음을 발견했습니다. 

연구 대상 지역마다 상당한 차이가 있지만, 

연구 결과에 따르면 

남성 4명 중 1명은 평생 동안 전립선 비대증으로 고통받을 것으로 보입니다. 

이 연구는 지식에 상당한 격차가 있음을 보여 주었으며, 이를 통해 향후 연구에서 데이터를 통해 역학 지형을 더욱 풍부하게 할 수 있는 기회를 제공할 수 있습니다.

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Introduction

Benign prostatic hyperplasia (BPH) is one of the most common urological diseases among men1. It is characterised by a benign overgrowth of prostatic tissue around the urethra which ultimately constricts the urethral opening, resulting in lower urinary tract symptoms (LUTS). Symptoms associated with LUTS include urgency, frequency, nocturia, incomplete urination, and weak urinary stream2. If left untreated, complications such as urinary retention, renal insufficiency and bladder stone can occur, requiring surgical intervention. BPH has also been associated with other medical morbidities, such as increased risk of falls3, reduced quality of life4 as well as increased annual healthcare cost5. As such, an understanding of the epidemiology of BPH is essential in health service planning as well as risk factor epidemiology.

Several longitudinal population based studies have provided some insights into the risk of BPH symptoms and progression. For example, the Olhmsted County study found that there was an increasing preval‎ence of moderate to severe symptoms of LUTS in men, increasing from 13% in men aged 40 to 49 years and 28% in men older than 70 years6. This number is expected to increase over the next few decades, mainly due to the increase in number of geriatrics as well as life expectancy. Several scholarly narrative reviews have been recently published in the past decade on the preval‎ence of BPH, but there has been substantial variation in the reported preval‎ence, ranging from 14% to 30% for men aged 50 or older depending on the definition used7,8,9. Many factors are thought to influence the clinical profile of patients presenting with BPH, including the differences in treatment culture, health service utilisation, degree of urbanisation and ethnicity.

Unfortunately, much of these data is heterogeneous, with variable methodological quality. In addition, most of these studies have yet to be subjected to the rigour of a systematic review and meta-analysis. This lack of synthesis makes it difficult for healthcare professionals and government officials to apply these any findings in their daily practice and public health planning. In the present study, we conducted a systematic review and meta-analysis to provide an initial baseline estimate of the preval‎ence of BPH in men worldwide and determine the various factors that are thought to influence the variations in reported preval‎ence.

소개

양성 전립선 비대증(BPH)은

남성에게 가장 흔한 비뇨기과 질환 중 하나입니다1.

이 질환은

요도 주변의 전립선 조직이 양성으로 과도하게 성장하여

궁극적으로 요도 입구를 수축시켜

요로 증상(LUTS)을 유발하는 것이 특징입니다.

LUTS와 관련된 증상으로는

절박뇨,

빈뇨,

야뇨증,

불완전 배뇨,

약한 배뇨2 등이 있습니다.

치료하지 않고 방치하면

요폐, 신장 기능 부전, 방광 결석과 같은 합병증이 발생하여

수술이 필요할 수 있습니다.

또한,

BPH는

낙상 위험 증가3,

삶의 질 저하4,

연간 의료비 증가5와 같은 다른 건강상의 문제와도 관련이 있습니다.

따라서 BPH의 역학에 대한 이해는 위험 인자 역학뿐만 아니라 의료 서비스 계획에도 필수적입니다.

여러 종단적 인구 기반 연구에서 BPH 증상 및 진행의 위험성에 대한 통찰력을 제공했습니다. 예를 들어, 올햄스테드 카운티 연구에 따르면, 40~49세 남성의 13%에서 70세 이상 남성의 28%로 증가하는 등, 남성에서 중등도에서 중증의 LUTS 증상이 점점 더 많이 발생하는 것으로 나타났습니다6. 이 수치는 향후 수십 년 동안 증가할 것으로 예상되는데, 이는 주로 노인 인구의 증가와 기대 수명의 증가에 기인합니다. 지난 10년 동안 전립선비대증의 유병률에 관한 여러 학술 논문이 발표되었지만, 보고된 유병률에는 상당한 차이가 있었는데, 50세 이상의 남성에서 14%에서 30%에 이르는 것으로 나타났습니다. 이는 사용된 정의에 따라 차이가 발생합니다7,8,9. 치료 문화, 의료 서비스 이용, 도시화 정도, 민족성 등 여러 요인이 전립선 비대증 환자의 임상 프로파일에 영향을 미치는 것으로 여겨집니다.

불행히도, 이러한 데이터의 대부분은 방법론적 품질이 다양하고 이질적입니다. 게다가, 이러한 연구의 대부분은 아직 체계적인 검토와 메타분석의 엄격한 과정을 거치지 않았습니다. 이러한 종합적인 분석의 부족으로 인해 보건의료 전문가와 정부 관계자들이 일상적인 업무와 공중보건 계획에 이러한 연구 결과를 적용하는 것이 어렵습니다. 본 연구에서는 전 세계 남성들의 전립선비대증 유병률에 대한 초기 기준 추정치와 보고된 유병률의 변화에 영향을 미치는 것으로 여겨지는 다양한 요인을 결정하기 위해 체계적인 검토와 메타분석을 실시했습니다.

Results

This systematic review identified a total of 31 studies6, 10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39 with sufficiently suitable data (Fig. 1) obtained from 25 countries. They comprised of fourteen published population based studies, thirteen community based studies, as well as four published studies estimated from clinic based cohorts. Twelve took place in Asia, 11 in Western Europe, 6 in North America and 2 in Australia and New Zealand and 1 in Africa. The number of participants per study varied considerably, ranging from 288 to 26,446 participants and all participants included were aged 30 years and above (Table 1).

결과

이 체계적인 검토를 통해

총 31건의 연구가 확인되었습니다6, 10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,2 5,26,27,28,29,30,31,32,33,34,35,36,37,38,39

25개국에서 얻은 충분히 적절한 데이터(그림 1)를 사용했습니다. 이 데이터는 14개의 인구 기반 연구, 13개의 커뮤니티 기반 연구, 그리고 클리닉 기반 코호트에서 추정된 4개의 연구로 구성되어 있습니다. 12개는 아시아에서, 11개는 서유럽에서, 6개는 북미에서, 2개는 호주와 뉴질랜드에서, 1개는 아프리카에서 진행되었습니다. 연구당 참가자 수는 288명에서 26,446명에 이르기까지 매우 다양했으며, 포함된 모든 참가자는 30세 이상(표 1)이었습니다.

Figure 1

Flow of the study.

Full size image

Table 1 Summary of studies which examined the preval‎ence of benign prostatic hyperplasia.

Full size table

Most of the included studies in the current review were cross sectional which had gathered data prospectively from surveys or interviews. These surveys can cover the whole country, as in the case of study with Egan and colleagues38, or a specific geographical area within the country, such as Shanghai in China39. The case definition of LUTS/BPH varied substantially across studies, depending on the criteria used. Ten studies used both objective as well as subjective parameters including measurement of prostate size as well as uroflowmetry while seventeen studies relied solely upon the presence of moderate to severe LUTS. Four studies only used objective measurements as the case definition for LUTS/BPH. The most common tool used for measuring severity of LUTS was the AUA -SI or IPSS, which was used in 24 studies, while 2 studies used a urinary dysfunction questionnaire and 1 used the Madsen questionnaire. When using the modified Newcastle-Ottawa quality assessment criteria, 2 studies received the maximum 5 points, 11 received 4 points, 7 received 3 points, 6 received 2 points and 5 received 1 point (Supplementary Table S1).

Epidemiology

In general, the preval‎ence of BPH increases with increasing age, with the highest preval‎ence in participants aged 70 and above. The median point preval‎ence was 25.2% and the 10% and 90% quartiles ranged from 19.0% to 37.9%. The highest preval‎ence of BPH was reported by Naslund and colleagues31 who surveyed patients from their clinic from 6 US states in 2007 while the lowest preval‎ence was found in Da and colleagues in Shanghai, China39. Meta-analysis of 30 studies using a random effects model yielded a summary preval‎ence of 26.2% (16,437/76,246 individuals; 95% CI: 22.8–29.8%). However, a high level of heterogeneity was observed (I 2 = 99.2%, Q-value = 3493.89, τ = 0.01, p < 0.01). Serial exclusion of each study in the sensitivity analysis demonstrated that no individual study influenced the overall preval‎ence by more than 1% (Supplementary Table S2).

To provide a range of BPH preval‎ence estimates due to the methodologically diverse studies, estimates were stratified according to diagnostic criteria and study level characteristics. When eval‎uated by BPH diagnostic criteria, summary preval‎ence estimates ranged from 26.2% for studies that used only objective measurements (798/2,837 individuals, 95% CI, 22.8–29.6%, Q = 3.60, τ2 = 0.001, I 2 = 44.5%) to 28.8% when using only subjective questionnaires such as the AUA-SI or the IPSS (8,417/28,421 individuals, 95% CI, 25.2–32.3%, Q = 654.93, τ2 = 0.006, I 2 = 97.7%). In the 11 studies that used both objective and subjective questionnaires, it yielded a lower preval‎ence estimates of 22.6% (7,221/44,723 individuals, 95% CI: 18.4–26.9%, Q = 877.60, τ2 = 0.005, I 2 = 98.9%).

Higher preval‎ence estimates were found among studies conducted in the United States versus elsewhere (3,765/14,284, 29.2% [95% CI, 22.3% to 36.1%] vs 12,672/61,962, 25.5% [95% CI, 21.5% to 29.4%]; Q = 0.85, P = 0.36), but this was not statistically significant. Similarly, no statistically significant difference in preval‎ence estimates were noted when stratified between rural, urban or mixed populations (Q = 0.58, p = 0.90), comparing respondent representativeness (Q = 0.04, p = 0.85), cohort sample size (Q = 0.01, p = 0.99) or study quality (Q = 0.22, p = 0.64). However, the preval‎ence rate was much lower in the study conducted among Africans compared to those conducted among Asian or Caucasians (Q = 101.34, p < 0.01). In the meta-regression analysis, none of the covariates analysed were significantly associated were associated with heterogeneity of preval‎ence estimates (Table 2).

역학

일반적으로,

BPH의 유병률은 나이가 들수록 증가하며,

70세 이상 참가자의 유병률이 가장 높습니다.

유병률의 중앙값은 25.2%였고, 10% 및 90% 사분위수는 19.0%에서 37.9%까지였습니다.

BPH의 가장 높은 유병률은 2007년 미국 6개 주에 있는 병원의 환자들을 대상으로 설문조사를 실시한 Naslund와 동료들이 보고한 바 있으며, 가장 낮은 유병률은 중국 상하이의 Da와 동료들이 보고한 바 있습니다39. 랜덤 효과 모델을 사용한 30개 연구의 메타 분석 결과, 요약 유병률은 26.2%(16,437/76,246명, 95% CI: 22.8–29.8%)로 나타났습니다. 그러나 높은 수준의 이질성이 관찰되었습니다(I 2 = 99.2%, Q-값 = 3493.89, τ = 0.01, p < 0.01). 민감도 분석에서 각 연구를 연속적으로 배제하는 과정에서 개별 연구가 전체 유병률에 1% 이상 영향을 미치지 않는다는 사실이 입증되었습니다(보충표 S2).

방법론적으로 다양한 연구로 인해 BPH 유병률 추정치의 범위를 제공하기 위해, 진단 기준과 연구 수준 특성에 따라 추정치를 계층화했습니다. BPH 진단 기준에 따라 평가했을 때, 객관적 측정만을 사용한 연구의 경우, 26.2%(798/2,837명, 95% CI, 22.8–29.6%, Q = 3.60, τ2 = 0.001, I 2 = 44.5%)에서 26.2%의 유병률을 추정했습니다. AUA-SI 또는 IPSS와 같은 주관적 설문지만을 사용할 경우 28.8%(8,417/28,421명, 95% CI, 25.2–32.3%, Q = 654.93, τ2 = 0.006, I 2 = 97.7%). 객관적 설문지와 주관적 설문지를 모두 사용한 11개 연구에서 22.6%(7,221/44,723명, 95% CI: 18.4–26.9%, Q=877.60, τ2=0.005, I 2=98.9%)의 낮은 유병률 추정치가 나왔습니다.

미국에서 실시한 연구에서 다른 나라에 비해 더 높은 유병률 추정치가 발견되었습니다(3,765/14,284, 29.2% [95% CI, 22.3% ~ 36.1%] vs 12 ,672/61,962, 25.5% [95% CI, 21.5% to 29.4%]; Q = 0.85, P = 0.36), 그러나 이것은 통계적으로 유의미하지 않았습니다. 마찬가지로, 농촌, 도시 또는 혼합 인구 집단을 구분할 때 응답자 대표성(Q=0.04, p=0.85), 코호트 표본 크기(Q=0.01, p=0.99) 또는 연구 품질(Q=0.22, p=0.64)을 비교할 때 유병률 추정치에 통계적으로 유의미한 차이가 발견되지 않았습니다. 그러나 아프리카인을 대상으로 한 연구에서 유병률은 아시아인이나 백인을 대상으로 한 연구에 비해 훨씬 낮았습니다(Q=101.34, p<0.01). 메타 회귀 분석에서 분석된 공변량 중 어느 것도 유병률 추정치의 이질성과 유의미한 관련이 없었습니다(표 2).

Table 2 Association between study variables and BPH preval‎ence estimates.

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Age specific preval‎ence

Of the total 31 studies, only 25 studies reported age-specific stratified data for analysis. Grouped summary data showed that there was an increasing preval‎ence of LUTS/BPH with age, with a pooled preval‎ence of 14.8%, 20.0%, 29.1%, 36.8% and 38.4% for age groups of 40–49 years, 50–59 years, 60–69 years, 70–79 years and 80 years and above respectively (Fig. 2), but there was a high level of heterogeneity.

연령별 유병률

총 31건의 연구 중 25건의 연구만이 연령별 계층화된 데이터를 분석에 보고했습니다. 그룹화된 요약 데이터에 따르면, 연령이 증가함에 따라 LUTS/BPH의 유병률이 증가하는 것으로 나타났으며, 14.8%, 20.0%, 29.1%, 36.8%, 38.4%의 유병률을 보였습니다. 연령 그룹은 각각 40-49세, 50-59세, 60-69세, 70-79세, 80세 이상(그림 2)으로 나뉘지만, 이질성이 높았습니다.

Figure 2

Unadjusted benign prostatic hyperplasia preval‎ence based across different age groups.

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Preval‎ence rates across the years

The preval‎ence rates of BPH for the survey years of 1990–1999, 2000–2009, and 2010 till present were 26.6%, 27.8% and 22.8% respectively. The preval‎ence rates were not significantly change with baseline survey year (slope = −0.24% per calendar year increase; 95% CI: −0.71 to 0.23; p = 0.30; Fig. 3). No significant interaction was detected when we tested the interactive effects with different study characteristics, suggesting that preval‎ence estimates were not affected by time in geographical regions or study methods.

Figure 3

Benign prostatic hyperplasia preval‎ence by year of data collection.

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Sensitivity analyses

Sensitivity analyses showed that there was very little difference in preval‎ence estimates when studies were excluded sequentially, or stratified by sample size and study quality. However, visual inspection of funnel plot was asymmetrical, suggesting that there was some evidence for bias due to small-study effects (Supplementary Fig. S1).

Discussion

BPH is a common condition that affects millions of men worldwide. In this study, we systematically reviewed studies to estimate the preval‎ence of BPH. We found that the pooled preval‎ence was 26.2% (95% CI: 22.8–29.6%), with estimates differing across studies, because of different BPH definitions, survey methods, response options, geographical locations and sample populations. Despite this, we found that the preval‎ence of BPH increases as patient age increase, from 14.8% in younger males aged 40 to 36.8% in males aged 80 and above. In most traditional preval‎ence studies, estimates are usually obtained based upon the population living in a specified area. However, this introduces a selection bias to the study as these boundaries (e.g., cities, county or even nations) may be suboptimal for the detection of variation of disorder between or even within a specific population. Similarly, factors such as age or even migration patterns can influence these estimate. The preval‎ence of BPH is also thought to vary across difference ethnicities, urban/rural settings and countries. Some of these differences may be attributable to the methodological differences but these variation does exist even in a multinational study which had identical BPH definitions, survey and response format. We also found that there was considerable variability even within studies in the same country. These differences may result from many different sociocultural and environmental factors that can affect prostate health, in addition to genetic factors.

Some potential reasons for the marked difference in estimated preval‎ence could be due to the methodological differences used by different studies. For example, in the study by Trueman and colleagues25, the presence of BPH was assessed using a self-administered questionnaire. In contrast, a study by Goh and associates40 in Korea reported a preval‎ence rate of 20%. Participants were surveyed by trained investigators and prostate disease was assessed by a physical examination and measurement of prostate volume and serum prostate specific antigen. The current AUA guideline defines LUTS/BPH as the presence of voiding and/or storage symptoms41. The absence of a specific, universally accepted operational criterion has led to a diversity of definition and variance in incidence estimates. These methodological differences are in part, likely to account for some of the differences in findings between studies.

The definition of BPH has been problematic due to the variation in case definition used by different studies. In many older studies identified, BPH is commonly described as a chronic urinary symptom experienced by elderly men. However, some studies had defined BPH using radiographically determined prostate enlargement, while others had used the definition of decreased in urinary flow rates, urinary symptoms and in some cases physician-diagnosed BPH. However, the most commonly used measures by which BPH is diagnosed are the AUA-SI and its internationally validated counterpart, the IPSS. This heterogeneity in BPH definition is thought to account for some differences in BPH preval‎ence rates.

The significant heterogeneity observed in this study led to a subgroup analysis as well as a meta-regression analyses to determine the potential sources. Effect estimates were similar when studies were grouped according to patient characteristics, suggesting that much of the heterogeneity remains unexplained. As with most meta-analysis of summary data, this study failed to identify the main source of heterogeneity. However, the meta-regression approach has several drawbacks. Firstly, it uses only the average value of a particular characteristic rather than individual values, thus decreasing the power to detect associations. Secondly, the meta-analysis also depended on the availability of published data, and more often than not, most of the methodology is incomplete.

This study has several strengths. To our knowledge, this is the first meta-analysis that attempts to examine and summarise the global preval‎ence of BPH. This systematic review conforms to the guidelines of Meta-Analysis of Observational Studies in Epidemiology (MOOSE)42 recommendations. Another strength of this study include a comprehensive and broad search strategy, as well as relevance of finding to clinical practice and research.

This study has some limitations. Firstly, as mentioned, the differences in study methodology and population may have considerable effects on the results. These effect contribute to the substantial variability in reported BPH rates, and it is difficult, if not impossible to separate these effects from the true geographical, cultural, economic and psychosocial differences. Secondly, we also restricted our search to only articles published in English, and thus we may have missed some important data. We did not search “grey literature”, as we felt that most of these data would not be sufficiently informative43. The current study could not take in consideration other risk factors associated with LUTS/BPH including diet, diabetes, or even body mass index which has substantially changed over the past 3 decades. Similarly, this study could not account for the variation in criteria of LUTS/BPH that has been revised. As such, inclusion of older studies may have led to an underestimation of the preval‎ence rates.

In summary, the current review provides a benchmark on the preval‎ence estimates for BPH. However, the wide range of preval‎ence estimates and case definition suggest that a standard criteria needs to be applied given the importance of understanding the preval‎ence of BPH and its implication on public health given the increasingly rapid growth of elderly worldwide. Additional research is needed in various areas especially on economic parameters.

토론

BPH는 전 세계 수백만 명의 남성에게 영향을 미치는 흔한 질환입니다. 이 연구에서는 BPH의 유병률을 추정하기 위해 체계적으로 연구를 검토했습니다. 연구 결과, BPH의 유병률은 26.2%(95% CI: 22.8–29.6%)로 조사되었으며, BPH의 정의, 조사 방법, 응답 옵션, 지리적 위치 및 표본 모집단의 차이로 인해 연구마다 추정치가 달랐습니다. 그럼에도 불구하고, 우리는 환자의 나이가 증가함에 따라 BPH의 유병률이 증가한다는 사실을 발견했습니다. 40세 미만의 젊은 남성에서 14.8%에서 80세 이상의 남성에서 36.8%로 증가했습니다. 대부분의 전통적인 유병률 연구에서는 특정 지역에 거주하는 인구를 기준으로 추정치를 얻습니다. 그러나 이러한 경계(예: 도시, 카운티 또는 국가)는 특정 인구 집단 간 또는 특정 인구 집단 내의 장애 변이를 감지하는 데 최적화되어 있지 않을 수 있으므로 연구에 선택 편향이 발생합니다. 마찬가지로, 연령 또는 이주 패턴과 같은 요인이 이러한 추정치에 영향을 미칠 수 있습니다. BPH의 유병률은 민족, 도시/농촌 환경, 국가에 따라 차이가 있는 것으로 여겨집니다. 이러한 차이 중 일부는 방법론적 차이에 기인할 수 있지만, BPH의 정의, 설문조사 및 응답 형식이 동일한 다국적 연구에서도 이러한 차이가 존재합니다. 또한 같은 국가 내의 연구에서도 상당한 차이가 있음을 발견했습니다. 이러한 차이는 유전적 요인 외에도 전립선 건강에 영향을 미칠 수 있는 다양한 사회문화적, 환경적 요인에 기인할 수 있습니다.

예상 유병률에 큰 차이가 나는 이유는 여러 연구에서 사용한 방법론의 차이에 기인할 수 있습니다. 예를 들어, Trueman과 동료들의 연구25에서는 자가진단 설문지를 사용하여 BPH의 유병률을 평가했습니다. 반면, 한국의 Goh와 동료들의 연구40에서는 20%의 유병률을 보고했습니다. 훈련된 조사관이 참가자들을 대상으로 설문조사를 실시했고, 전립선 질환은 신체 검사 및 전립선 부피와 혈청 전립선 특이 항원 측정을 통해 평가되었습니다. 현재의 AUA 지침은 배뇨 및/또는 저장 증상의 존재를 LUTS/BPH로 정의하고 있습니다41. 보편적으로 인정되는 구체적인 운영 기준이 없기 때문에 정의가 다양해지고 발생률 추정치가 달라지게 되었습니다. 이러한 방법론적 차이는 부분적으로 연구 간의 결과 차이의 일부를 설명할 수 있습니다.

BPH의 정의는 여러 연구에서 사용하는 사례 정의의 차이로 인해 문제가 되어 왔습니다. 확인된 많은 오래된 연구에서 BPH는 일반적으로 노인 남성이 겪는 만성 비뇨기 증상으로 묘사됩니다. 그러나 일부 연구에서는 방사선 촬영으로 결정된 전립선 비대를 사용하여 BPH를 정의한 반면, 다른 연구에서는 요로 흐름 속도 감소, 비뇨기 증상, 그리고 일부 경우 의사가 진단한 BPH의 정의를 사용했습니다. 그러나, BPH 진단에 가장 일반적으로 사용되는 방법은 AUA-SI와 국제적으로 검증된 IPSS입니다. BPH의 정의가 이처럼 다양하다는 것은 BPH의 유병률에 약간의 차이가 있다는 것을 설명하는 것으로 여겨집니다.

이 연구에서 관찰된 상당한 다양성은 잠재적 원인을 파악하기 위한 하위 그룹 분석과 메타 회귀 분석을 이끌어냈습니다. 환자 특성에 따라 연구를 그룹화했을 때 효과 추정치가 비슷하다는 것은 다양성의 상당 부분이 설명되지 않은 채로 남아 있음을 시사합니다. 대부분의 요약 데이터 메타 분석과 마찬가지로, 이 연구는 이질성의 주요 원인을 파악하지 못했습니다. 그러나 메타 회귀 분석 방식에는 몇 가지 단점이 있습니다. 첫째, 개별 값이 아닌 특정 특성의 평균값만 사용하므로 연관성을 감지하는 능력이 떨어집니다. 둘째, 메타 분석은 발표된 데이터의 가용성에 의존하기 때문에, 대부분의 방법론이 불완전합니다.

이 연구는 여러 가지 장점이 있습니다. 우리가 아는 한, 전립선비대증의 전 세계적인 유병률을 조사하고 요약하려는 최초의 메타분석입니다. 이 체계적인 검토는 역학 관찰 연구의 메타분석(MOOSE)42 권고사항의 지침을 준수합니다. 이 연구의 또 다른 장점은 포괄적이고 광범위한 검색 전략과 임상 실습 및 연구와의 관련성을 포함합니다.

이 연구에는 몇 가지 제한이 있습니다. 첫째, 앞서 언급했듯이 연구 방법론과 모집단의 차이는 결과에 상당한 영향을 미칠 수 있습니다. 이러한 영향은 보고된 BPH 비율의 상당한 변동성에 기여하며, 이러한 영향을 실제 지리적, 문화적, 경제적, 심리사회적 차이와 분리하는 것은 불가능하지는 않더라도 어렵습니다. 둘째, 우리는 또한 영어로 출판된 논문으로 검색을 제한했기 때문에 중요한 데이터를 놓쳤을 수 있습니다. 우리는 “그레이 리터러시(grey literature)”를 검색하지 않았습니다. 그 이유는 이러한 자료의 대부분이 충분한 정보를 제공하지 못할 것이라고 생각했기 때문입니다43. 현재의 연구는 식이요법, 당뇨병, 심지어 지난 30년 동안 크게 변화한 체질량 지수(BMI)를 포함하여 LUTS/BPH와 관련된 다른 위험 요소를 고려할 수 없었습니다. 마찬가지로, 이 연구는 개정된 LUTS/BPH 기준의 변동을 설명할 수 없었습니다. 따라서, 이전 연구가 포함되면서 유병률의 과소평가가 초래되었을 수 있습니다.

요약하면, 현재의 검토는 BPH의 유병률 추정치에 대한 기준을 제공합니다. 그러나, 유병률 추정치와 사례 정의의 폭이 넓다는 것은 전 세계적으로 고령 인구의 증가가 가속화되고 있는 상황에서 BPH의 유병률과 공중 보건에 미치는 영향을 이해하는 것이 중요하다는 점을 감안할 때 표준 기준을 적용해야 한다는 것을 시사합니다. 특히 경제적인 변수에 관한 다양한 영역에서 추가적인 연구가 필요합니다.

Methods

Search strategy and selection criteria

We performed a literature search up until 31 July 2016 using a combination of search terms (Appendix 1) on the following database: Pubmed, EMBASE, Cinahl plus, AMED, CENTRAL and Web of Science for articles describing the preval‎ence of BPH among males. Keywords used include: preval‎ence, incidence, prostate enlargement, benign prostate hyperplasia, benign prostatic hypertrophy, bladder outlet obstruction and lower urinary tract symptoms. Two authors independently (SWHL & EMCC) reviewed the records to identify for potentially studies and full text of studies were retrieved if necessary. We also manually search bibliographies of included studies and any relevant review articles for additional references. In the event of multiple publications of identical data, the most informative version of the study was used. Any discrepancies were resolved by open discussion.

Definition

While the term BPH is correctly defined as histopathological hyperplastic changes in the prostate41, most studies and clinicians commonly use the term to describe a clinical syndrome that comprised of LUTS, prostatic enlargement and bladder outlet obstructions. In this study, we used the case definition for BPH as stated in the study. In the event that this was not stated, BPH was defined as the presence of moderate to severe LUTS, and used a cut off score of >7 for the American Urological Association Symptom Index (AUA-SI)44 or the shorter version International Prostate Symptom Score (IPSS). Countries were regarded as industrialised if they fell within the high income definition as defined by the World Health Organisation.

Data extraction and assessment

Two authors separately extracted the studies using a standardised extraction template, including study level characteristics (e.g., urban/rural, study design, year study was conducted, definition of BPH and data collection methods) as well population characteristics (e.g., age-specific rates and ethnicity/race). Study authors were contacted for data clarification if necessary. The methodological quality of each study was judged using a modified version of the Newcastle-Ottawa Scale45, which includes 4 criteria namely, sample representativeness and size, comparability between respondents and non-respondents, ascertainment of BPH symptoms and statistical quality. Studies were judged to be low risk of bias if they had a minimum score of 3 points of the maximum 5 points.

Statistical analysis

We conducted a meta-analysis of incidence data and pooled the estimates and 95% confidence intervals (CI) using the metaprop command developed by the Unit Cancer Epidemiology in Brussel46, and used the random-effects model since we expect the presence of heterogeneity. We subsequently conducted a subgroup analysis, and stratified the studies according to study geographic regions, number of cases of BPH, tools used to detect BPH as well as age groups as reported by the study. Potential small study publication bias was assessed using the Begg & Eggers test, as well as visual inspection of the funnel plot. Between studies heterogeneity was assessed using I2 and Cochran’s Q method. In the event of substantial heterogeneity, a random-effects meta-regression analysis was conducted to determine the effects of variables such as population demographics, study characteristics and indicators of error or bias on preval‎ence estimates. Any factor(s) which was significant in the univariate analysis were included into a multiple regression model. We also performed several sensitivity analyses to assess how our primary estimates differed when we excluded studies sequentially as well as studies with lower methodological quality such as those with poor sampling methods or sample sizes less than 1000 participants. We also assessed the possibility of change in preval‎ence patterns over time by examining preval‎ence rates across different study years. All analyses was conducted using Stata version 13.0 (StataCorp, College TX).

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