A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation

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1 Alimentary Pharmacology & Therapeutics A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation A. WALD*, C. SCARPIGNATO, S. MUELLER-LISSNERà, M.A.KAMM,U.HINKEL, I.HELFRICH, C. SCHUIJT &K.G.MANDEL** *Section of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Laboratory of Clinical Pharmacology, Department of Human Anatomy, Pharmacology and Forensic Sciences, University of Parma, Parma, Italy; àpark-klinik Weissensee, Humboldt University, Berlin, Germany; St Vincent s Hospital and Melbourne University, Melbourne, Australia, and Imperial College, London, UK; Department of Medicine, Consumer Healthcare, Boehringer Ingelheim GmbH, Ingelheim, Germany; **KGM Innovation Associates, Inc., Fairfield, OH, USA Correspondence to: Ulrika Hinkel, Boehringer Ingelheim GmbH, CD Medicine Medicine CHC, Ingelheim am Rhein, Germany. ulrika.hinkel@boehringeringelheim.com Publication data Submitted 27 March 2008 First decision 6 April 2008 Resubmitted 26 June 2008 Accepted 14 July 2008 Epub Accepted Article 17 July 2008 SUMMARY Background While numerous studies report prevalence of constipation, use of laxatives is poorly understood. Aim To conduct a survey in seven countries evaluating prevalence of constipation and laxative use in its treatment. Methods Thirteen thousand eight hundred seventy-nine adults [approximately 2000 each from US, UK, Germany (GE), France (FR), Italy (IT), Brazil (BR) and South Korea (SK)] completed questionnaires assessing occurrence, frequency, duration and laxative use for treating constipation. Results Overall, 12.3% of adults had constipation [range: 5% (GE) to 18% (US)] in the prior year. A greater percent of women from all countries and elderly from all except SK and BR reported constipation; odds ratios for constipation among women and elderly were 2.43 (95% CI: ) and 1.5 (95% CI: ) vs. men and young subjects. Among those with constipation, 16% (SK) to 40% (US) used laxatives. Laxative use was generally associated with increasing age, symptom frequency and lower income and education. A similar percentage of men and women with constipation reported using laxatives; a greater percentage of women used laxatives for a longer time. Conclusions Prevalence of self-defined constipation and laxative use varies among countries. Prevalence is generally related to gender and age, whereas laxative use is related to age, but not to gender. Aliment Pharmacol Ther 28, ª 2008 Boehringer Ingelheim GmbH 917 doi: /j x

2 918 A. WALD et al. INTRODUCTION Constipation is a common disorder, which patients usually define as straining, difficulty in passing stool, hard stool, infrequent bowel movements, discomfort with defecation and feeling of incomplete evacuation. In contrast, constipation is often clinically defined by healthcare professionals based only on bowel frequency, specifically, having fewer than three bowel movements per week. 1 The Rome Criteria provide a clinical definition of constipation based on objective (stool frequency, requiring manual manoeuvres for defecation) and subjective (straining, hard stool, incomplete bowel movements, sensing anorectal blockage) symptoms. 2 These criteria provide a means to standardize diagnostic evaluation and are useful for identifying patients for research studies and clinical trials. Several studies report population prevalence of constipation to range from 2% to 28% This wide range, in part, reflects how constipation is defined and the populations surveyed. In general, estimates of prevalence rates are lower in studies, which use more restricted definitions for constipation. For example, defining constipation solely as having a stool frequency of fewer than three bowel movements per week results in lower prevalence rates ranging from <1% to 5.4%. In contrast, higher prevalence rates are reported when constipation is defined using combinations of subjective (straining, passing hard stool, having unsatisfactory or incomplete defecation) and objective (stool frequency) measures. 9, Drossman et al. 9 reported prevalence rates of 17.2% and 4.2% when constipation was defined as straining on >25% of bowel movements, or <3 bowel movements per week respectively. Similarly, studies defining constipation, based on a combination of objective and subjective symptoms or using the Rome Criteria, report prevalence rates ranging from 8.0% to 18.3% and higher prevalence 13, 15, 16 in women than in men. Other studies have measured prevalence based on self-defined constipation, where participants are free to consider themselves to have constipation without any constraint on definition. The estimation of the community prevalence of constipation based on selfdefinition relies on the finding that most sufferers do not seek healthcare intervention. As expected, the prevalence of self-defined constipation is greater than that reported using restricted definitions, such as stool frequency alone. 8, 11, For example, Curtin et al. 8 reported prevalence rates of 6.4%, 5.1% and 2% in Swiss adult males when constipation was self-defined, defined as straining and or difficulty in evacuation, or as having <3 bowel movements per week respectively. Another study from Sweden reported a 14.3% prevalence when constipation was self-defined, but only 3.1% when defined as <3 bowel movements per week. 11 Surveys conducted in representative US population samples reported prevalence of self-reported constipation to range from 17, % to 20.8%. Most studies also demonstrate that individuals define constipation primarily as symptoms of straining, hard stool, discomfort and difficulty in passing stool, in contrast to a clinical definition based solely on infrequent stool frequency. In addition, most epidemiologic studies support evidence that constipation occurs with greater frequency in women than in men and that prevalence generally increases with age. 1, 3, 5, 15, 17, Some studies also support an association between increased prevalence of constipation, lower education and lower socioeconomic status. Population-based studies from the US suggest higher prevalence among women than among men and African-Americans compared with 17, 18 Caucasians. In contrast to the large amount of data concerning the prevalence of constipation and its association with age and gender, relatively little is known about laxative use among constipation sufferers. In the mid-1960s, Connell et al. 1 reported a constipation prevalence of <1%, but laxative use of almost 20% in a UK population sample. This suggests a large discrepancy between laxative use and reported constipation. To our knowledge, no study to date has been published, which compares prevalence of constipation and use of laxatives amongst various countries using the same survey methodology. This study compares prevalence rates of self-reported constipation and use of laxatives by constipation sufferers in seven countries, namely the United States (US), United Kingdom (UK), France (FR), Germany (GE), Italy (IT), Brazil (BR) and South Korea (SK). Participants from each country were interviewed using an appropriately translated standardized questionnaire. Results of the present investigation clearly show similarities and differences across geographies for this common gastrointestinal (GI) disorder and for laxative use.

3 LAXATIVE USE IN SELF-DEFINED CONSTIPATION 919 METHODS The research was conducted as part of an ongoing international Omnibus survey conducted through IPSOS, a global marketing research company. Depending on the individual country, the surveys were conducted at intervals of at least once weekly to once per month. The methodology does not allow the same individuals to participate in sequential surveys. These surveys are conducted in national population samples representative of each country s demographics for age, gender, household income and regions. The individual studies include standardized questions on demographics and specialized questions on unrelated and noninterfering topics. Approximately 2000 subjects each from the US, UK, FR, GE, IT, BR and SK were targeted to complete interviews and provide analysable data. Data were collected by computer-assisted telephone interview (US, SK) or by individual interviews conducted by trained moderators in which data were either directly entered into a computer (GE, FR, IT, UK) or collected on paper forms (BR). Data from the US, UK, FR, GE and IT were collected from national representative population samples. In BR, subjects were selected from four regions (areas of Sao Paulo, Rio de Janeiro, Recife and Porto Alegre). The tested population is considered, with the exception of extremely isolated regions, representative for the country, and included subjects from both rural and urban regions. Subjects from SK were from six regions (Seoul, Busan, Teague, Inchon, Kwanju and Deajon). For countries in which data were obtained from one-on-one interviews (UK, GE, FR, IT, BR), subjects were randomly identified by sampling from publicly available national census databases. These provided addresses and information on population demographics. The latter was used to stratify contacts lists. In the US and SK, subjects were interviewed by telephone and were contacted using a random dialing strategy. The research methodology does not provide the percent of subjects who could not be contacted or who, if contacted, refused participation. No demographics are available for subjects who refused participation. Identical questionnaires, appropriately translated into local languages, were used in all countries. While the questions on constipation and laxative use were not specifically validated or tested for reliability, the questions were simple and based on similar questionnaires reported in the literature used to study constipation in population-based studies for many years. Furthermore, market research and epidemiology studies demonstrate that constipation is well understood by the general population. Finally, the translations were checked for accuracy regarding the questions and answer choices. Questions regarding constipation assessed whether subjects had experienced symptoms of constipation during the prior year. Those who answered positively completed subsequent questions related to duration of constipation symptoms (<3, 3 to <10, 10 years), the frequency of symptoms during the past year (once or more weekly, <once weekly but at least once every 3 months, <once every 3 months) and habits and practices for managing constipation. The latter include doing nothing until symptoms resolved, making lifestyle changes and using laxatives. The term laxative was not predefined, nor were subjects provided with a list of laxative products to prompt their response. Subjects reporting use of laxatives were assessed regarding the duration and frequency of laxative use. Duration and frequency of laxative use was assessed using the same multicategory scale used to assess constipation duration and frequency. Statistical analyses were conducted using SAS software package (SAS Institute, Inc., Raleigh, NC, USA). Univariate and multivariate methodologies assessed factors contributing to the presence or absence of constipation in the full study population. Categorical differences were tested by chi-squared statistics and contributions of demographic factors to symptoms were assessed using a multiple regression model. Statistical significance was set at 0.05 using two-tailed tests. RESULTS Demographics Demographics for the total population sample from each country and for subjects reporting constipation during the past year are summarized in Table 1. Thirteen thousand eight hundred seventy-nine subjects, 2000 each from the US, FR, GE, IT, BR and SK and 1879 from the UK (121 subjects refused to answer questions related to their health status), completed the interview and provided analysable data. The overall population included 7182 women (51.75%; range 50% in SK to 52.2% in GE) and 6697 men (48.25%; range 47.8% in UK and GE to 50% in SK) at least 15 years of age. Overall, 27%, 29%, 24% and 21% of respondents were 29, 30 44, and 60 years of age respectively, but because of general population

4 920 A. WALD et al. Table 1. Demographics of study population and respondents reporting to have constipation in past year Total Constipated Total Constipated Total Constipated Total Constipated Total Constipated Total Constipated Total Constipated No. of respondents Gender, n (%) Female 1037 (51.8) 222 (62.9) 980 (52.1) 107 (73.8) 1040 (52.0) 197 (70.4) 1044 (52.2) 78 (72.9) 1041 (52.1) 112 (70.4) 1040 (52.0) 252 (75.5) 1000 (50.0) 227 (68.0) Male 963 (48.2) 131 (37.1) 899 (47.9) 38 (26.2) 960 (48.0) 83 (29.6) 956 (47.8) 29 (27.1) 959 (47.9) 47 (29.6) 960 (48.0) 82 (24.5) 1000 (50.0) 107 (32.0) Age (years) (%) < > Work status (%) Yes Education* (%) < College University Income (%) Low Middle High All values are from demographic data collected during interviews conducted in each of the seven countries [United States (US), United Kingdom (UK), France (FR), Germany (GE), Italy (IT), Brazil (BR) and South Korea (SK)]. For each country, Total and Constipated represent responses for the total number of interviewed subjects and those who self-report having constipation during the past 12 months respectively. For each category, percentages are based on number of respondents. Totals that do not equal 100% represent rounding errors. * Education levels are assigned as: <high school or secondary school degree (<2 ), having high school or secondary school degree and or having attended college, but not having a university degree (2 ), and having a college or postgraduate degree (College University). Income levels are assigned as low, medium and high and reflect ranges for the lowest to highest average tertile incomes for each country.

5 LAXATIVE USE IN SELF-DEFINED CONSTIPATION 921 statistics, only 12% and 7% of subjects from BR and SK were 60 years of age. Constipation prevalence and associated factors As shown in Table 1, 1712 subjects reported having constipation symptoms in the past 12 months. Constipation was more often reported by women (n = 1195; 69.8% of those having constipation; range 62.9% in US to 75.5% in BR) than by men (n = 517; 30.2%; range 24.5% in BR to 37.1% in US). Prevalence for self-defined constipation ranged from 5.4% in GE to 17.7% in the US. As shown in Figure 1, the prevalence of self-defined constipation was higher in women in all countries, with prevalence rates ranging from 7.5% in GE to 24.2% in BR. In comparison, prevalence was much lower in men, ranging from 3.0% in GE to 13.6% in the US. Women were 2.4-fold more likely to have constipation than men [OR: 2.43; 95% confidence interval (95% CI): ; P < 0.05]. As also shown in Table 1, compared to individuals 29 years of age, the probability of having constipation increased significantly among those aged (OR 1.16; 95% CI: ), (OR 1.19; 95% CI: ) and 60 years (OR: 1.47; 95% CI: ) (all P < 0.05), in all countries except SK and BR. Using GE as a reference, subjects from SK aged 60 or older were 50% less likely (OR: 0.56; 95% CI: ), whereas those in the US aged 60 or older were 1.7-fold more likely (OR: 1.69; 95% CI: ) to have constipation (both, P = ). Constipation prevalence (%) Females Males Country Figure 1. Prevalence of self-defined constipation is greater amongst women than amongst men in each of the countries surveyed. See Table 1 for numbers of male and female respondents. Constipation associated with reduced activity (OR: 1.23; 95% CI: ; P < 0.05) was most evident in the US and Europe. In GE, IT, UK, FR and US, 65%, 58%, 57%, 54% and 46% of subjects with constipation more often reported being inactive, compared to 52%, 50%, 46%, 42% and 38% of nonconstipated subjects. In contrast, in BR and SK, less than 16% and 11% of those with or without constipation were inactive. For all countries, subjects who completed less than secondary-level education had a significantly higher likelihood for constipation than those with secondary level education (OR: 1.20; 95% CI: ; P < 0.03) and a trend for increased likelihood for constipation compared with those having a college or university degree (OR 1.20; 95% CI: ; P < 0.08). Among individual countries, the association between increased likelihood for constipation and lower education achieved statistical significance for FR (OR: 1.48; 95% CI: ; P < 0.05) and the US (OR 1.82; 95% CI: ; P < 0.01). In contrast, in BR, compared with subjects having a college degree, those with lower education had a lower likelihood for constipation (OR: 0.58; 95% CI: ; P < 0.03). A similar trend was observed between income and constipation. Across all countries, subjects having lower income had a significantly greater likelihood for constipation than those with middle income (OR: 1.33; 95% CI: ; P < 0.002) and a trend for increased constipation compared to those with income in the highest tertile (OR: 1.15; 95% CI: ; P < 0.13). Among individual countries, these associations were largely directional and did not achieve statistical significance, except for GE (low vs. middle income; P < 0.003). Table 2 summarizes the association, by country and gender, of constipation with age. In the US, UK, FR, GE, IT and BR, but not SK, increasing prevalence with age was observed amongst men and women. In addition to having constipation, participants were asked if, during the prior year, they also experienced GI symptoms such as abdominal cramps or pain, bloating, flatulence gas, heartburn and or nausea and vomiting. With the exception of IT, subjects with constipation also had significantly more concomitant GI symptoms than did those without constipation. The largest difference was seen in the US. In descending order of frequency, constipation was associated significantly with flatulence gas (OR: 6.1; 95% CI: ) > bloating (OR: 5.2; 95% CI: ) > abdominal cramps pain (OR: 4.3; 95% CI: ) > nausea (OR: 3.9; 95% CI:

6 922 A. WALD et al. Table 2. Association of age with constipation prevalence amongst women and men in each of the seven countries Females Males Country Cohort (years) n total n const (%) n total n const (%) Prevalence Prevalence US UK FR GE < IT BR SK For abbreviations see the footnotes of Table 1. The table summarizes the prevalence of self-defined constipation among men and women from each of the seven studied counties, by age cohorts. n total is the number of men and women interviewed within each age cohort. n const is the number of men and women self-reporting to have constipation symptoms in the past 12 months within each age cohort. Prevalence is assessed as (n const n total ) ) > vomiting (OR: 3.1; 95% CI: ), gastritis (OR: 3.1; 95% CI: ) and heartburn (OR: 3.0; 95% CI: ); all P < Frequency and duration of self-reported constipation Frequency and duration of self-reported constipation is summarized in Table 3. The frequency of having constipation symptoms at least once a week ranged from 30% to 71% in the seven countries, with the highest frequency reported for IT. In general, women from all countries reported having constipation more frequently than men, with the greatest differences in FR and GE where 52% and 41% of women, but only 27% and 17% of men respectively, reported having constipation at least once a week. In contrast to an association between increasing age with increasing prevalence of constipation, we did not observe any clear association between the frequency of constipation and age (data not shown). The duration of constipation symptoms is also summarized in Table 3. The prevalence of those

7 LAXATIVE USE IN SELF-DEFINED CONSTIPATION 923 Table 3. The number of respondents is the number of females and males reporting to have had constipation symptoms in the past year. Symptom frequency and duration are reported as the percent of females and males who provided responses within the indicated ranges. Percentages which do not add to 100% represent rounding errors and or lack of response by some subjects. Frequency and Duration of Self-Reported Constipation Symptoms Total # Respondents (n) Symptom Frequency (% all with constipation reporting to have symptoms) Daily to 1X wk < 1X wk to 1X mnth <1X mnth Symptom Duration (% all with constipation reporting to have symptoms) For up to 3 years For more than 3 yrs Female Male Female Male Female Male Female Male Female Male Female Male Female Male # Respondents (n) Symptom Frequency (% females and males reporting to have symptoms) Daily to 1X wk < 1X wk to 1X mnth <1 X mnth , Symptom Duration (% females and males reporting to have symptoms) For up to 3 years For more than 3 yrs who reported constipation and who had symptoms for at least 3 years ranged from 39% in the UK to 67% in IT. Overview of constipation treatment As shown in Figure 2, in all countries except the UK, the most common action for managing constipation was to change lifestyle, with 39% (GE) to 58% (US) of respondents reporting using lifestyle changes in response to constipation. The primary lifestyle changes were eating healthier foods and drinking more water liquids. Compared with the other countries, fewer subjects from the UK and BR altered lifestyle to treat constipation; the UK was the only country in which lifestyle change was a less frequent option than using laxatives. While increasing activity exercise was one component of lifestyle change, few subjects reported doing so for constipation. Medical intervention, primarily use of laxatives, ranged from 16% in SK to 40% in the US. In this survey, use of laxatives was defined as any pharmaceutical intervention for management of symptoms. Among all countries, only %Respondents Do nothing Change lifestyle Use laxative US UK FR GE Country IT BR SK Figure 2. Actions taken in response to constipation symptoms. Subjects from each country were asked to indicate typical actions taken when constipation occurs. Response categories shown in the figure are: do nothing (no intervention wait for symptoms to resolve; solid bars), make lifestyle changes (alter diet, drink more fluids; hatched bars) and use laxatives (shaded bars). Multiple answers were allowed, so the total for each country can exceed 100%. Numbers of constipated subjects are given in Table 3.

8 924 A. WALD et al. a minority of individuals having constipation reported not taking any interventional action, but rather allowing symptoms to resolve spontaneously. Use of laxatives in treating constipation Table 4 summarizes laxative use among constipated men and women by country and age cohort. There were no consistent differences in laxative use between men and women. For example, a greater percent of women than men in FR (35% vs. 28%), GE (33% vs. 24%) and BR (34% vs. 17%) used laxatives, while a higher percent of men than of women used laxatives in IT (47% vs. 30%) and US (44% vs. 38%). In contrast to gender, increased laxative use was associated with increasing age in all countries except SK and BR. As shown in Table 4, with the exception of SK and BR, among those having constipation, a greater percent of both men and women 60 years of age and older reported to use laxatives compared with younger subjects. However, the study populations for SK and BR included fewer elderly participants (see Table 2). There was also greater variability in the relationship between age and laxative use among men with constipation, but this may reflect inclusion of fewer men in this cohort. Two factors, age and country, were found to have a significant association with laxative use. After adjusting for other factors (gender, country, working status and constipation duration and frequency), subjects 60 years of age and older were 1.6-fold (OR: 1.63; 95% CI: ) more likely to use laxatives compared with those in the youngest age cohort (P = ). Figures 3 and 4 show the association of laxative use with the duration and frequency of constipation in the seven countries. The longer the duration of constipation, the higher the likelihood of laxative use. With the exception of FR, a greater percentage of subjects from all other countries who used laxatives, also reported having constipation for 3 years or more (Figure 3). Across all countries, 60% of those who used laxatives, and 48% of those who did not, reported having constipation for at least 3 years (P < ). The greatest difference was in GE, where 76% of laxative users had constipation for at least 3 years; in contrast, only 39% of those in GE who do not use laxatives reported having had constipation for this duration of time (P = ). Laxative use also showed an association with symptom frequency (Figure 4). In the US, FR, BR and SK, a somewhat higher percentage of subjects who used laxatives Table 4. Association of laxative use for treating constipation with gender and age % by Gender Females 38.3% 34.6% 35.0% 33.3% 29.5% 33.7% 15.9% Males 43.5% 39.5% 27.7% 24.1% 46.8% 17.1% 16.8% % by Age (years) % 15.4% 26.2% 16.7% 29.0% 28.7% 19.2% % 30.8% 22.1% 8.7% 25.0% 31.2% 12.9% % 37.1% 20.9% 28.0% 25.0% 30.0% 14.0% % 51.1% 47.7% 43.4% 50.0% 27.3% 22.7% M F M F M F M F M F M F M F % by Age (years) and gender For abbreviations see the footnotes of Table 1. All values are from data collected during interviews conducted in each of the seven countries. Total numbers of men and women from each country having constipation are reported in Table 3. Among those reporting to have constipation, 142, 52, 92, 33, 55, 99 and 54 subjects from the US, UK, FR, GE, IT, BR and SK respectively, also reported to use laxatives. In general, use of laxatives increases amongst both men and women 60 years or age and older.

9 LAXATIVE USE IN SELF-DEFINED CONSTIPATION 925 % w/constipation 3 years or more Use laxative Do not use laxative Country Figure 3. For all countries except FR, a greater percentage of subjects who reported to use laxatives also reported having suffered from constipation symptoms for 3 years or longer. Bars show the percentage of subjects from each country reporting to have had constipation for 3 years or more who used (solid bars) or did not use (shaded bars) laxatives for treatment of constipation. % w/constipation at least weekly Use laxative Do not use laxative Country Figure 4. For all countries except GE and IT, a greater percentage of subjects who reported to use laxatives also reported having symptoms at least once a week. Bars show the percentage of subjects from each country reporting to have constipation once weekly or more who used (solid bars) or did not use (shaded bars) laxatives. reported having constipation symptoms at least weekly compared to non-users. Overall, 51% of laxative users reported having symptoms at least weekly, compared to 45% of those who did not use laxatives. As shown in Table 5, women also reported having used laxatives for a longer time than men. Overall, almost 30% of women who used laxatives had used them for at least 10 years compared to 11.5% of men. Longer duration of laxative use by women was observed in all countries evaluated in this survey. Table 6 presents associations between education and income with use of laxatives in treating constipation. For all countries, subjects having completed less than secondary-level education had a significantly higher likelihood to use laxatives compared with those having completed secondary (OR: 1.73; 95% CI: ; P < ) or college education (OR 2.32; 95% CI: ; P < ). This was significant in FR (<secondary vs. college: OR: 5.00; 95% CI: ; P < ; secondary vs. college: OR: 2.58; 95% CI: ; P < 0.05), IT (<secondary vs. college: OR: 2.28; 95% CI: ; P < 0.03), UK (<secondary vs. college: OR: 3.37; 95% CI: ; P < 0.03) and the US (<secondary vs. college: OR: 2.29; 95% CI: ; P < 0.05; secondary vs. college: OR: 1.75; 95% CI: ; P < 0.02). Among all countries, there was a significant association of increased use of laxatives with lower income levels (low vs. high income: OR: 1.66; 95% CI: ; P < 0.007; middle vs. high income: OR: 1.68: 95% CI: ; P < 0.007). As shown in the Table, in the US, FR, GE, IT and SK, laxative use was higher amongst subjects having the lowest income levels, whereas subjects having high income were more likely not to use laxatives to treat constipation. The strongest association between increased laxative use and income was observed in FR where having low or middle income increased the likelihood of laxative use by 3.3- and 4.5-fold respectively, compared to those with high income (low vs. high income: OR: 3.33; 95% CI: ; P < 0.001; middle vs. high income: OR: 4.49; 95% CI: ; P < ). In the US, subjects having low income showed a trend for increased use of laxatives (low vs. high income: OR: 1.68; 95% CI: ; P = 0.054). In contrast to the other countries, use of laxatives in BR was lower among individuals with low and middle income compared with those in the highest income bracket. Finally, constipated subjects who used laxatives were evaluated as to their frequency of laxative use. Figure 5 shows, for each country, the percentage of men and women with self-defined constipation who used laxatives more than and less than once a month. Almost 72% of women and 59% of men, who used laxatives, did so at least monthly. Women in all countries showed a trend for using laxatives more frequently than men. The greatest gender difference was observed in GE where 73% of women and 43% of men who used laxatives for constipation reported using them at least once monthly. In contrast, a similar percentage of men and

10 926 A. WALD et al. Table 5. Duration of laxative use among men and women Female Male Female Male Female Male Female Male Female Male Female Male Female Male No. of laxative users (n) Duration of laxative use (% reporting) Up to 3 years years years or longer For abbreviations see the footnotes of Table 1. The number of respondents is the number of females and males using laxatives for treatment of constipation symptoms. Duration of laxative use is reported as having used laxatives for up to 3 years, between 3 and 10 years and for longer than 10 years. Percentages that do not add to 100% represent rounding errors and or lack of response by some subjects. Table 6. Association of laxative use with education and income level Use laxatives (yes no) Yes No Yes No Yes No Yes No Yes N Yes No Yes No n Education level (% responding) <2 Education 10.7* * * Education 57.1à à College University Income level (% responding) Low Middle High For abbreviations see the footnotes of Table 1. The number of respondents is the number of subjects with constipation who reported to use (yes) or not use (no) laxatives. Education and income levels are as defined for Table 1. Statistically significant difference between education levels: * <secondary vs. college; <secondary vs. secondary; à secondary vs. college. Statistically significant difference between income levels: low vs. high; middle vs. high. women from the US and IT who used laxatives, reported doing so at least monthly. Conversely, with the exception of the US and IT, a greater percentage of men than women reported less frequent use (less than once per month) of laxatives. Overall, 26% and 37% of women and men reported using laxatives less than once monthly to treat constipation. DISCUSSION This is the first multinational survey that describes associations between constipation and use of laxatives and provides new information on factors including gender, age, education and income, and frequency and duration of constipation symptoms, which may influence the use of laxatives by constipation sufferers. We did not, in this study, define the term laxative in the questionnaire; rather, subjects self-defined laxatives. Among the seven countries surveyed, availability and accessibility based on laxatives being marketed as prescription or nonprescription drugs, or having purchase costs reimbursed by healthcare insurers may have impacted decisions by subjects to use these products. However, this was not addressed in the brief questionnaire used in this survey and to our knowledge, we are unaware of other information, which may address these factors. In addition, the survey methodology did not document the number of subjects who refused participation in any of

11 LAXATIVE USE IN SELF-DEFINED CONSTIPATION 927 % Reporting frequency of laxative use Country Figure 5. Frequency of laxative use among female and male laxative users for each country. Numbers of laxative users are reported in Table 3. Frequency of laxative use is reported as once per month or more among women (solid bars) and men (shaded bars) and less than once monthly among women (hatched bars) and men (open bars), respectively. the seven countries, nor were demographic data available for the nonparticipants. Depending on the country, the survey collected data either by personal or by telephone interviews. While a possible impact of the interview methods cannot be excluded, we feel that this would be minimal. Indeed, constipation prevalence and sociodemographic associations observed in this study are similar to those reported in prior surveys. One consistent observation is that, in all countries, less than half of all constipated subjects (from 16% in SK to 40% in the US) reported using laxatives. Due to variations in how laxatives are marketed in the different countries and in the roles of physicians and pharmacists in providing them, it was not possible to determine whether products taken were prescription or nonprescription (over-the-counter) medications. Differences in availability of, and access to laxatives, may also have affected decisions regarding their use. In addition, different countries have different policies regarding reimbursement of pharmaceutical products, which also may affect usage. These issues were not addressed in this survey. Other measures for treating constipation also showed general consistencies across countries. For example, lifestyle change, specifically improving diet and increasing fluid intake, was the most common treatment for constipation reported in all countries, except the UK. Interestingly, Müller-Lissner et al. recently reviewed the association of low fibre intake and low fluid intake as causative factors for constipation. These authors concluded that low fibre intake, while potentially contributory, cannot be assumed to be the cause of chronic constipation in most individuals. In addition, there is little data to support an association between low fluid intake and constipation, nor are there data that constipation can be successfully treated by increasing fluid intake. 23 Although we observed no overall effect of gender on laxative use, there were differences among countries. In FR, GE and BR, more women than men reported using laxatives to treat constipation, whereas the opposite was observed in IT, the US and the UK. Overall, women reported using laxatives for longer periods of time. We also found that with the exception of SK and BR, laxative use increased with ageing. Among individuals with constipation, those aged 60 years and older were 1.6-fold more likely to use laxatives than those <30 years of age. This was similar to observations in a study conducted in the UK in which 11.6% and 22.6% of men and women between 60 and 69 years reported using laxatives for constipation compared to 3.4% and 13.5% of men and women years of age respectively. 24 Ruby et al. 25 surveyed Caucasians and Blacks from a single region in the US and reported 10.2% of those 65 years of age or older using laxatives, with women having over 1.7- fold greater likelihood for laxative use. Using a broader US population-based sample, we observed that 11.1% of adults aged 60 and over used laxatives, a rate similar to that reported by Ruby et al. We also observed an increased prevalence of laxative use among US women over 60 years of age. In our study, regression analysis demonstrated that only two factors, age and country, were significantly associated with laxative use. We found that women used laxatives with a greater frequency than men in all countries. We also observed associations between education and income with both constipation and use of laxatives. Across all countries, lower income and education levels were associated with increased likelihood of constipation. This was especially true in FR and the US, whereas in BR, constipation was more prevalent amongst those with higher education. Previous studies conducted among US and Australian adults and adult Swiss men have reported associations of lower income and or education with higher prevalence of constipation. 3, 5, 8, 17, 18, 22, 26 Similarly, in all countries, there were significant associations between having lower income and education and increased use

12 928 A. WALD et al. of laxatives. In all countries except the UK and BR, a higher percent of laxative users were in the lowest income bracket compared with subjects having constipation and not using laxatives. Whether differences observed between countries reflect healthcare access, the ability and or income to purchase laxatives or other factors is not understood. Although we allowed subjects to self-define constipation, the prevalence rates reported in this study, which ranged from 5.3% in GE to 17.6% in the US, are similar to those reported in previously published epidemiologic studies, mostly conducted in single countries and primarily in the US. 4 7, 11, 14, 19 The prevalence rates observed in this study are similar to surveys conducted in the US, Sweden, Switzerland and Taiwan and from a multinational European survey published in abstract form. 8, 11, 17, 19, 27 As this survey utilized identical questionnaires for each country, the variation in prevalence rates observed probably represents true differences among countries. Other published epidemiology studies have found a greater prevalence of constipation in women and the elderly. 3, 4, 7, 15, 17, 18, 21, 28 We also found women were 2.4-fold more likely to have constipation than men, similar to gender-related differences reported in other population-based epidemiology studies. 5, 11 However, a survey of an older Asian population from Singapore did not observe such gender differences. 29 As we surveyed a younger population sample from SK, there is a need for additional studies of other Asian populations. With the exception of SK and BR, constipation prevalence increased with age among both men and women. Similar to our observation, studies in US residents have also reported a higher prevalence of constipation among older US residents The lower prevalence of constipation observed in our elderly cohort from SK and the slightly higher prevalence observed with increasing age among women in BR may reflect the lower percent of elderly from these respective countries who participated in our survey. In all countries except IT, subjects having constipation reported a significantly greater number of other GI symptoms, including abdominal cramping and pain, bloating, flatulence, heartburn and nausea vomiting (all P < 0.01). This has also been reported by others. 20 Subsequent studies have shown a consistent association of constipation and constipation-predominant IBS with increased reporting of other lower GI symptoms (discomfort, flatulence, etc.) as well as upper GI symptoms often associated with dyspepsia This study provides new information regarding the association of laxative use with constipation. Only a minority of constipated subjects in this study reported using laxatives for treatment. Laxative use also was associated with having more frequent constipation symptoms and symptoms that have persisted over a longer period of time. This also needs to be confirmed in additional studies. Understanding whether duration, frequency or specific symptoms of constipation are associated with use of different types of laxatives, such as stimulant, bulking or osmotic laxatives will be the subject of future studies. As discussed above, allowing subjects to self define constipation often provides a higher prevalence rate than when using a definition based primarily on a low frequency of bowel movements. The recently published Rome III criteria define functional constipation based on a collection of symptoms including bowel frequency, straining, hard stool, incomplete evacuation and the need to use manual manoeuvres to complete stooling. 2 Recently, we presented data from a subsequent survey of subjects with self-defined criteria who were administered the Rome questionnaire. Seventy percent (FR) to 95% (BR) of subjects having selfreported constipation also fulfilled two or more Rome III criteria for functional constipation. 37 As a consequence, results of this study should have appropriate clinical relevance. In conclusion, this multinational survey reporting patterns of laxative use among constipation sufferers from seven countries demonstrates country-specific differences based on gender, duration of constipation and an impact of other sociodemographic factors. In all countries, only a minority of subjects reporting to have constipation also reported to use laxatives for treatment. In some, but not in all countries, more women than men having constipation reported using laxatives and overall, women reported using laxatives for longer periods of time than men. In most countries, use of laxatives increased with ageing. There was also a general association for increased use of laxatives among those with lower income and education. Differences between countries, especially the observations from BR and SK, should be further investigated in future studies, which could also evaluate additional countries within South America and Asia. Further research should assess other factors, such as accessibility and cost, which may impact decisions to use laxatives in the treatment of constipation.

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