Introduction: Constipation is one of the most common gastrointestinal symptoms. It may compromise quality of life and social functioning and result in increased healthcare use and costs. We aimed to evaluate the prevalence and risk factors of constipation symptoms, as well as those of refractory constipation symptoms among patients who underwent colonoscopy. Methods: Over 4.5 years, patients who underwent colonoscopy and completed questionnaires were analyzed. Patients’ symptoms were evaluated using the Gastrointestinal Symptoms Rating Scale. Results: Among 8,621 eligible patients, the prevalence of constipation symptoms was 33.3%. Multivariate analysis revealed female sex (odds ratio [OR] 1.7, p < 0.001), older age (OR 1.3, p < 0.001), cerebral stroke with paralysis (OR 1.7, p = 0.009), chronic renal failure (OR 2.6, p < 0.001), ischemic heart disease (OR 1.3, p = 0.008), diabetes (OR 1.4, p < 0.001), chronic obstructive pulmonary disease (OR 1.5, p = 0.002), benzodiazepine use (OR 1.7, p < 0.001), antiparkinsonian medications use (OR 1.9, p = 0.030), and opioid use (OR 2.1, p = 0.002) as independent risk factors for constipation symptoms. The number of patients taking any medication for constipation was 1,134 (13.2%); however, refractory symptoms of constipation were still present in 61.4% of these patients. Diabetes (OR 1.5, p = 0.028) and irritable bowel syndrome (OR 3.1, p < 0.001) were identified as predictors for refractory constipation symptoms. Conclusions: Constipation occurred in one-third of patients, and more than half of patients still exhibited refractory symptoms of constipation despite taking laxatives. Multiple medications and concurrent diseases seem to be associated with constipation symptoms.

Constipation is one of the most common gastrointestinal symptoms in adults [1]; the prevalences are approximately 16% in adults overall and 33% in adults older than 60 years [2]. Approximately 30% of the general population experiences problems with constipation during their lifetime [2]. A total of 51.5% of Japanese people recognized that they currently experienced constipation, as evaluated through an internet survey [3].

Constipation compromises the quality of life, social functioning, and ability to perform activities of daily living, possibly resulting in an increased burden on the healthcare system [4]. Furthermore, constipation symptoms are reportedly associated with a higher risk of all-cause mortality [5, 6].

The prevalence of laxative use, as evaluated through a national survey of an Australian community, was 37% [7], and it increased five-folds in 10 years [8]. Recently, various agents, such as linaclotide and lubiprostine, have been approved for the alleviation of chronic constipation. Despite these advancements in medical treatment for constipation, a subset of patients continues to have constipation symptoms refractory to laxatives.

Various risk factors, including older age, female sex, colon cancer, diabetes, Parkinson’s disease, stroke, and medication use (such as opioids and antidepressants), have been reportedly associated with constipation) [6, 9‒14]. However, the characteristics and risk factors for refractory constipation remain unknown. Thus, this study aimed to address the prevalence and risk factors of constipation and refractory constipation among patients undergoing colonoscopy.

Study Design, Setting, and Participants

We conducted a hospital-based retrospective study using an electronic endoscopic database (SolemioEndo, Olympus, Japan). Patients who underwent colonoscopy at the National Center for Global Health and Medicine (NCGM), Tokyo, Japan, between October 2015 and March 2020 were requested to complete questionnaires before endoscopy. The indication for colonoscopy was determined by each gastroenterologist. The following patients were excluded: those who did not complete the questionnaires (n = 9,052) and those who presented with colon cancer, inflammatory bowel disease, or history of lower gastrointestinal (GI) surgery (n = 2,081). After excluding these patients, data from cohort of 8,621 patients was analyzed. This study was approved by the Ethics Committee of the National Center for Global Health and Medicine (approval no. NCGM-004078).

Questionnaires on Demographic Characteristics and Comorbidities

The detailed questionnaire consisted of four parts: demographics, comorbidities, currently used medications, and GI symptoms. Demographic data included age, sex, height, body weight, and body mass index (BMI). The comorbidities included diabetes, intracerebral hemorrhage, cerebral stroke with paralysis, ischemic heart disease, chronic renal failure treated with hemodialysis, dementia, collagen vascular disease, and chronic obstructive pulmonary disease (COPD).

Currently Used Medications

The patients were requested to list all the currently used medications. Drugs of the same class were classified into one category. We verified whether the patients were taking any drugs, such as benzodiazepines, antipsychotics, antidepressants, antiparkinsonian medications, opioids, calcium channel blockers (CCBs), antiarrhythmic agents, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs), that could potentially induce constipation.

Evaluation of GI Symptoms

GI symptoms were evaluated using the Gastrointestinal Symptoms Rating Scale (GSRS), a self-administered questionnaire containing 15 questions. Each question was scored according to a 7-point Likert scale (1, no discomfort at all; 2, slight discomfort; 3, mild discomfort; 4, moderate discomfort; 5, moderately severe discomfort; 6, severe discomfort; and 7, very severe discomfort) over the preceding week [15‒17].

Definition of constipation symptoms: constipation-related symptoms were evaluated on the basis of two questions of the GSRS on constipation (reduced ability to empty the bowels) and hard stools. Constipation symptoms were defined as scores of ≥3 points for at least one of the constipation-related symptoms [18]. Definition of refractory constipation symptoms: among patients taking one or more medications for constipation (laxatives), refractory constipation symptoms were defined as persistent symptoms of constipation (scores ≥3 points for the questionnaire).

The diagnosis of irritable bowel syndrome (IBS) was made according to the Rome III criteria; that is, at least 3 months, with onset at least 6 months previously, of recurrent abdominal pain or discomfort associated with two or more of the following: improvement with defecation, and/or onset associated with a change in frequency of stool, and/or onset associated with a change in form (appearance) of stool [19].

Statistical Analysis

The Kolmogorov-Smirnov test was used to assess normality of continuous variables. Normally distributed variables were reported as mean (standard deviation), and skewed variables were reported as median (interquartile range). Categorical variables were reported as n (%).

All continuous data were skewed, and the non-parametric Mann-Whitney U test was used for comparison between patients with and without constipation. The χ2 Fisher’s exact test was used for categorical variables to compare the differences between groups.

Patient demographics and results are presented as medians and percentages for quantitative and categorical data, respectively. Univariate and multivariate analyses were performed using a logistic regression analysis with these factors. The odds ratios and 95% confidence intervals (CIs) were calculated for each variable. Statistical significance was set at p < 0.05. All statistical analyses were performed using SPSS Statistics software (version 26.0; IBM Corp., Armonk, NY, USA).

Patient Characteristics

During the study period, 8,621 patients were identified. Patient characteristics are presented in Table 1. Among 2,922 patients with constipation symptoms with a median age of 69.0 (IQR, 20) years, 49.8% (1,455/2,922) were female, and the median BMI was 22.4 (IQR, 4.5) kg/m2. The proportion of female patients with constipation symptoms stratified according to age groups was as follows: 65.1% among younger adults aged <40 years, 61.6% among patients in their 40s, 53.2% among patients in their 50s, 48.3% among patients in their 60s, 46.1% among patients in their 70s, and 39.4% among those aged ≥80 years. The prevalence rates of constipation symptoms stratified according to BMI groups were as follows: 39.9% among patients with BMI <18.5 kg/m2, 35.5% among those with BMI 18.5–22.0 kg/m2, 33.2% among those with BMI 22.0–25.0 kg/m2, and 30.2% among those with BMI ≥25 kg/m2. The most common comorbidities were diabetes (15.4%, 441/2,856) and ischemic heart disease (9.2%, 258/2,814). Many patients with constipation symptoms had been taking CCBs (23.4%, 684/2,922), benzodiazepines (15.9%, 464/2,922), and NSAIDs (8.0%, 235/2,922).

Table 1.

Patient demographics and clinical characteristics in patients with and without constipation

VariablesAll patients (n = 8,621)No constipation (n = 5,699)Constipation (n = 2,922)p value
Age, years, median (IQR) 66.0 (21) 65.0 (21) 69.0 (20) <0.001 
Age, n (%)    <0.001 
 ≥65 years 4,630 2,899 (62.6) 1,731 (37.4)  
 <65 years 3,991 2,800 (70.2) 1,191 (29.8)  
Sex, n (%)    <0.001 
 Female 3,586 2,131 (59.4) 1,455 (40.6)  
 Male 5,035 3,568 (70.9) 1,467 (29.1)  
BMI, kg/m2, median (IQR) 22.7 (4.5) 22.8 (4.5) 22.4 (4.5) <0.001 
BMI, n (%)    <0.001 
 <18.5 kg/m2 682 410 (60.1) 272 (39.9)  
 ≥18.5 kg/m2 7,748 5,172 (66.8) 2,576 (33.2)  
Comorbidities, n (%)     
 Diabetes    <0.001 
  + 1,083 642 (59.3) 441 (40.7)  
  − 7,386 4,971 (67.3) 2,415 (32.7)  
 Intracerebral hemorrhage    <0.001 
  + 354 204 (57.6) 150 (42.4)  
  − 8,052 5,370 (66.7) 2,682 (33.3)  
 Cerebral stroke with paralysis    <0.001 
  + 128 60 (46.9) 68 (53.1)  
  − 8,145 5,433 (66.7) 2,712 (33.3)  
 Ischemic heart disease    <0.001 
  + 621 363 (58.5) 258 (41.5)  
  − 7,753 5,197 (67.0) 2,556 (33.0)  
 Chronic renal failure    <0.001 
  + 91 41 (45.1) 50 (54.9)  
  − 8,318 5,536 (66.6) 2,782 (33.4)  
 Dementia    0.022 
  + 37 18 (48.6) 19 (51.4)  
  − 8,257 5,486 (66.4) 2,771 (33.6)  
 Collagen vascular disease    0.002 
  + 370 219 (59.2) 151 (40.8)  
  − 7,942 5,304 (66.8) 2,638 (33.2)  
 COPD    <0.001 
  + 311 168 (54.0) 143 (46.0)  
  − 8,087 5,400 (66.8) 2,687 (33.2)  
Medication, n (%) 
 Benzodiazepines    <0.001 
  + 960 496 (51.7) 464 (48.3)  
  − 7,661 5,203 (67.9) 2,458 (32.1)  
 Antipsychotics    <0.001 
  + 233 123 (52.8) 110 (47.2)  
  − 8,388 5,576 (66.5) 2,812 (33.5)  
 Antidepressants    <0.001 
  + 262 133 (50.8) 129 (49.2)  
  − 8,359 5,566 (66.6) 2,793 (33.4)  
 Antiparkinsonian agents    <0.001 
  + 65 29 (44.6) 36 (55.4)  
  − 8,556 5,670 (66.3) 2,886 (33.7)  
 Opioids    <0.001 
  + 98 43 (43.9) 55 (56.1)  
  − 8,523 5,656 (66.4) 2,867 (33.6)  
 CCBs    0.078 
  + 1,923 1,239 (64.4) 684 (35.6)  
  − 6,698 4,460 (66.6) 2,238 (33.4)  
 Antiarrhythmic agents    0.307 
  + 176 110 (62.5) 66 (37.5)  
  − 8,445 5,589 (66.2) 2,856 (33.8)  
 Diuretics    0.399 
  + 134 84 (62.7) 50 (37.3)  
  − 8,487 5,615 (66.2) 2,872 (33.9)  
 NSAIDs    0.010 
  + 608 373 (61.3) 235 (38.7)  
  − 8,013 5,326 (66.5) 2,687 (33.5)  
VariablesAll patients (n = 8,621)No constipation (n = 5,699)Constipation (n = 2,922)p value
Age, years, median (IQR) 66.0 (21) 65.0 (21) 69.0 (20) <0.001 
Age, n (%)    <0.001 
 ≥65 years 4,630 2,899 (62.6) 1,731 (37.4)  
 <65 years 3,991 2,800 (70.2) 1,191 (29.8)  
Sex, n (%)    <0.001 
 Female 3,586 2,131 (59.4) 1,455 (40.6)  
 Male 5,035 3,568 (70.9) 1,467 (29.1)  
BMI, kg/m2, median (IQR) 22.7 (4.5) 22.8 (4.5) 22.4 (4.5) <0.001 
BMI, n (%)    <0.001 
 <18.5 kg/m2 682 410 (60.1) 272 (39.9)  
 ≥18.5 kg/m2 7,748 5,172 (66.8) 2,576 (33.2)  
Comorbidities, n (%)     
 Diabetes    <0.001 
  + 1,083 642 (59.3) 441 (40.7)  
  − 7,386 4,971 (67.3) 2,415 (32.7)  
 Intracerebral hemorrhage    <0.001 
  + 354 204 (57.6) 150 (42.4)  
  − 8,052 5,370 (66.7) 2,682 (33.3)  
 Cerebral stroke with paralysis    <0.001 
  + 128 60 (46.9) 68 (53.1)  
  − 8,145 5,433 (66.7) 2,712 (33.3)  
 Ischemic heart disease    <0.001 
  + 621 363 (58.5) 258 (41.5)  
  − 7,753 5,197 (67.0) 2,556 (33.0)  
 Chronic renal failure    <0.001 
  + 91 41 (45.1) 50 (54.9)  
  − 8,318 5,536 (66.6) 2,782 (33.4)  
 Dementia    0.022 
  + 37 18 (48.6) 19 (51.4)  
  − 8,257 5,486 (66.4) 2,771 (33.6)  
 Collagen vascular disease    0.002 
  + 370 219 (59.2) 151 (40.8)  
  − 7,942 5,304 (66.8) 2,638 (33.2)  
 COPD    <0.001 
  + 311 168 (54.0) 143 (46.0)  
  − 8,087 5,400 (66.8) 2,687 (33.2)  
Medication, n (%) 
 Benzodiazepines    <0.001 
  + 960 496 (51.7) 464 (48.3)  
  − 7,661 5,203 (67.9) 2,458 (32.1)  
 Antipsychotics    <0.001 
  + 233 123 (52.8) 110 (47.2)  
  − 8,388 5,576 (66.5) 2,812 (33.5)  
 Antidepressants    <0.001 
  + 262 133 (50.8) 129 (49.2)  
  − 8,359 5,566 (66.6) 2,793 (33.4)  
 Antiparkinsonian agents    <0.001 
  + 65 29 (44.6) 36 (55.4)  
  − 8,556 5,670 (66.3) 2,886 (33.7)  
 Opioids    <0.001 
  + 98 43 (43.9) 55 (56.1)  
  − 8,523 5,656 (66.4) 2,867 (33.6)  
 CCBs    0.078 
  + 1,923 1,239 (64.4) 684 (35.6)  
  − 6,698 4,460 (66.6) 2,238 (33.4)  
 Antiarrhythmic agents    0.307 
  + 176 110 (62.5) 66 (37.5)  
  − 8,445 5,589 (66.2) 2,856 (33.8)  
 Diuretics    0.399 
  + 134 84 (62.7) 50 (37.3)  
  − 8,487 5,615 (66.2) 2,872 (33.9)  
 NSAIDs    0.010 
  + 608 373 (61.3) 235 (38.7)  
  − 8,013 5,326 (66.5) 2,687 (33.5)  

Missing data were noted in the following numbers of patients for each parameter: 191 for BMI, 152 for diabetes, 215 for intracerebral hemorrhage, 348 for cerebral stroke with paralysis, 247 for ischemic heart disease, 212 for chronic renal failure, 327 for dementia, 309 for collagen vascular disease, and 223 for COPD.

BMI, body mass index; CCBs, calcium channel blockers; COPD, chronic obstructive pulmonary disease; IQR, interquartile range; NSAIDs, nonsteroidal anti-inflammatory drugs.

Prevalence of Constipation Symptoms

The prevalence rates of decreased passage of stools and hard stools were 27.6% and 25.7%, respectively, and that of constipation symptoms was 33.3%. On the basis of the Rome III criteria, 75.4% of the patients with constipation symptoms had abdominal pain and discomfort, and among them, 64.7% reported that these symptoms decreased after passage of stool, 57% observed changes in the frequency of stool, and 68.8% observed changes in stool shape. The proportion of patients with IBS was 45.3% (IBS with constipation, 18.1%; IBS with mixed bowel habits, 27.2%) of the 2,922 patients with constipation symptoms (missing data in 198 patients).

Factors Associated with Constipation Symptoms

Univariate analyses revealed the following risk factors for constipation symptoms: older age (≥65 years old) (37.4%); female sex (40.6%); being underweight (BMI <18.5 kg/m2; 39.9%); chronic renal failure (54.9%); cerebral stroke with paralysis (53.1%); dementia (51.4%); COPD (46.0%); intracerebral hemorrhage (42.4%); ischemic heart disease (41.5%); collagen vascular disease (40.8%); diabetes (40.7%); and the use of opioids (56.1%), antiparkinsonian medications (55.4%), antidepressants (49.2%), benzodiazepines (48.3%), antipsychotics (47.2%), and NSAIDs (38.7%) (Table 1).

Multivariate logistic regression analysis revealed that older age (odds ratio [OR] 1.3 [95% CI: 1.1–1.4], p < 0.001), female sex (OR 1.7 [95% CI: 1.6–1.9], p < 0.001), chronic renal failure (OR 2.6 [95% CI: 1.7–4.2], p < 0.001), cerebral stroke with paralysis (OR 1.7 [95% CI: 1.1–2.6], p = 0.009), COPD (OR 1.5 [95% CI: 1.2–1.9], p = 0.002), ischemic heart disease (OR 1.3 [95% CI: 1.1–1.6], p = 0.008), diabetes (OR 1.5 [95% CI: 1.3–1.7], p < 0.001), opioid use (OR 2.1 [95% CI: 1.3–3.2], p = 0.002), antiparkinsonian medication use (OR 1.9 [95% CI: 1.1–3.2], p = 0.030), and benzodiazepine use (OR 1.7 [95% CI: 1.4–2.0], p < 0.001) were independent risk factors for constipation symptoms (Table 2).

Table 2.

Multivariate analysis of the risk factors for constipation symptoms

VariablesOR (95% CI)p value
Age  <0.001 
 <65 years 1.00 (reference)  
 ≥65 years 1.26 (1.14–1.39)  
Sex  <0.001 
 Male 1.00 (reference)  
 Female 1.73 (1.56–1.91)  
BMI  0.054 
 ≥18.5 1.00 (reference)  
 <18.5 1.19 (1.00–1.42)  
Comorbidities 
 Diabetes 1.45 (1.25–1.67) <0.001 
 Intracerebral hemorrhage 1.28 (0.99–1.64) 0.059 
 Cerebral stroke with paralysis 1.72 (1.14–2.60) 0.009 
 Ischemic heart disease 1.29 (1.07–1.56) 0.008 
 Chronic renal failure 2.62 (1.65–4.16) <0.001 
 Dementia 1.46 (0.69–3.07) 0.324 
 Collagen vascular disease 1.09 (0.86–1.37) 0.488 
 COPD 1.50 (1.16–1.93) 0.002 
Medications 
 Benzodiazepine 1.68 (1.44–1.98) <0.001 
 Antipsychotics 1.14 (0.83–1.57) 0.422 
 Antidepressants 1.32 (0.99–1.77) 0.062 
 Antiparkinsonian agents 1.86 (1.06–3.24) 0.030 
 Opioid 2.06 (1.32–3.23) 0.002 
 NSAIDs 1.06 (0.88–1.28) 0.559 
VariablesOR (95% CI)p value
Age  <0.001 
 <65 years 1.00 (reference)  
 ≥65 years 1.26 (1.14–1.39)  
Sex  <0.001 
 Male 1.00 (reference)  
 Female 1.73 (1.56–1.91)  
BMI  0.054 
 ≥18.5 1.00 (reference)  
 <18.5 1.19 (1.00–1.42)  
Comorbidities 
 Diabetes 1.45 (1.25–1.67) <0.001 
 Intracerebral hemorrhage 1.28 (0.99–1.64) 0.059 
 Cerebral stroke with paralysis 1.72 (1.14–2.60) 0.009 
 Ischemic heart disease 1.29 (1.07–1.56) 0.008 
 Chronic renal failure 2.62 (1.65–4.16) <0.001 
 Dementia 1.46 (0.69–3.07) 0.324 
 Collagen vascular disease 1.09 (0.86–1.37) 0.488 
 COPD 1.50 (1.16–1.93) 0.002 
Medications 
 Benzodiazepine 1.68 (1.44–1.98) <0.001 
 Antipsychotics 1.14 (0.83–1.57) 0.422 
 Antidepressants 1.32 (0.99–1.77) 0.062 
 Antiparkinsonian agents 1.86 (1.06–3.24) 0.030 
 Opioid 2.06 (1.32–3.23) 0.002 
 NSAIDs 1.06 (0.88–1.28) 0.559 

BMI, body mass index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; NSAIDs, nonsteroidal anti-inflammatory drugs; OR, odds ratio.

Factors Associated with Refractory Constipation Symptoms

Overall, 1,134 (13.2%) patients were taking constipation medications. The major laxatives were osmotic agents (686 patients; 60.5%), stimulant agents (384 patients; 33.9%), Japanese herbal Kampo medicine (193 patients; 17.0%), secretagogues including elobixibat (an ileal bile acid transporter inhibitor), linaclotide and lubiprostone (intestinal secretagogues) (60 patients; 5.3%), and bulk-forming agents (37 patients; 3.3%). Among these 1,134 patients, 827 used a single medication, 238 used two medications, and 69 patients used three medications or more. Despite taking these medications, refractory constipation symptoms were still present in 61.3% of patients. The prevalence of refractory constipation symptoms according to medication types used is shown in Figure 1. The prevalence of constipation symptoms tended to be increase with an increase in the number of medications taken by patients (57.8% among those taking a single medication, 69.7% among those taking two medications, 73.9% among those taking three medications or more).

Fig. 1.

Prevalence of refractory constipation symptoms according to medication (laxatives) types used. Secretagogues include elobixibat, linaclotide, and lubiprostone. Despite taking laxatives, refractory constipation symptoms were still present in 61.3% of the 1,134 patients.

Fig. 1.

Prevalence of refractory constipation symptoms according to medication (laxatives) types used. Secretagogues include elobixibat, linaclotide, and lubiprostone. Despite taking laxatives, refractory constipation symptoms were still present in 61.3% of the 1,134 patients.

Close modal

Univariate analysis showed that refractory constipation symptoms, despite the use of medications for constipation, were significantly more prevalent in patients with IBS (75.3%) and diabetes (68.7%) (Table 3). Multivariate analysis adjusted for age and sex also indicated that IBS (OR 3.1 [95% CI: 2.3–4.0], p < 0.001) and diabetes (OR 1.5 [95% CI: 1.0–2.2], p = 0.028) were predictors of refractory constipation symptoms (Table 4).

Table 3.

Univariate analysis of the risk factors for persistent constipation symptoms

VariablesPatients who used medications (n = 1,134)No constipation (n = 439)Constipation (n = 695)p value
Age, years, median (IQR) 71.0 (17) 72.0 (18) 71.0 (17) 0.980 
Age    0.901 
 ≥65 years 351 134 (38.2) 217 (61.8)  
 <65 years 783 305 (39.0) 478 (61.0)  
Sex    0.328 
 Female 620 248 (40.0) 372 (60.0)  
 Male 514 191 (37.2) 323 (62.8)  
BMI, kg/m2, median (IQR) 22.3 (4.5) 22.2 (4.6) 22.3 (4.3) 0.960 
BMI    0.989 
 <18.5 kg/m2 119 46 (38.7) 73 (61.3)  
 ≥18.5 kg/m2 984 381 (38.7) 603 (61.3)  
Comorbidities, n (%) 
 Diabetes    0.028 
  + 166 52 (31.3) 114 (68.7)  
  − 947 382 (40.3) 565 (59.7)  
 Intracerebral hemorrhage    0.936 
  + 60 23 (38.3) 37 (61.7)  
  − 1,045 406 (38.9) 639 (61.1)  
 Cerebral stroke with paralysis    0.126 
  + 28 7 (25.0) 21 (75.0)  
  − 1,061 417 (39.3) 644 (60.7)  
 Ischemic heart disease    0.477 
  + 120 43 (35.8) 77 (64.2)  
  − 980 384 (39.2) 596 (60.8)  
 Chronic renal failure    0.358 
  + 16 8 (50.0) 8 (50.0)  
  − 1,090 422 (38.7) 668 (61.3)  
 Dementia    0.278 
  + 11 6 (54.5) 5 (45.5)  
  − 1,080 416 (38.5) 664 (61.5)  
 Collagen vascular disease    0.285 
  + 81 27 (33.3) 54 (66.7)  
  − 1,001 394 (39.4) 607 (60.6)  
 COPD    0.810 
  + 67 27 (40.3) 40 (59.7)  
  − 1,038 403 (38.8) 635 (61.2)  
 IBS    <0.001 
  + 442 109 (24.7) 333 (75.3)  
     (IBS-C, 136; IBS-M, 197)  
  − 618 306 (49.5) 312 (50.5)  
Medications, n (%) 
 Benzodiazepines    0.239 
  + 301 108 (35.9) 193 (64.1)  
  − 833 331 (39.7) 502 (60.3)  
 Antipsychotics    0.948 
  + 73 28 (38.4) 45 (61.6)  
  − 1,061 411 (38.7) 650 (61.3)  
 Antidepressants    0.724 
  + 84 31 (36.9) 53 (63.1)  
  − 1,050 408 (38.9) 642 (61.1)  
 Antiparkinsonian agents    0.512 
  + 22 10 (45.5) 12 (54.5)  
  − 1,112 429 (38.6) 683 (61.4)  
 Opioids    0.744 
  + 44 16 (36.4) 28 (63.6)  
  − 1,090 423 (38.8) 667 (61.2)  
 CCBs    0.549 
  + 309 124 (40.1) 185 (59.9)  
  − 825 315 (38.2) 510 (61.8)  
 Antiarrhythmic agents    0.873 
  + 40 15 (37.5) 25 (62.5)  
  − 1,094 424 (38.8) 670 (61.2)  
 Diuretics    0.400 
  + 26 8 (30.8) 18 (69.2)  
  − 1,108 431 (38.9) 677 (61.1)  
 NSAIDs    0.111 
  + 126 57 (45.2) 69 (54.8)  
  − 1,008 382 (37.9) 626 (62.1)  
VariablesPatients who used medications (n = 1,134)No constipation (n = 439)Constipation (n = 695)p value
Age, years, median (IQR) 71.0 (17) 72.0 (18) 71.0 (17) 0.980 
Age    0.901 
 ≥65 years 351 134 (38.2) 217 (61.8)  
 <65 years 783 305 (39.0) 478 (61.0)  
Sex    0.328 
 Female 620 248 (40.0) 372 (60.0)  
 Male 514 191 (37.2) 323 (62.8)  
BMI, kg/m2, median (IQR) 22.3 (4.5) 22.2 (4.6) 22.3 (4.3) 0.960 
BMI    0.989 
 <18.5 kg/m2 119 46 (38.7) 73 (61.3)  
 ≥18.5 kg/m2 984 381 (38.7) 603 (61.3)  
Comorbidities, n (%) 
 Diabetes    0.028 
  + 166 52 (31.3) 114 (68.7)  
  − 947 382 (40.3) 565 (59.7)  
 Intracerebral hemorrhage    0.936 
  + 60 23 (38.3) 37 (61.7)  
  − 1,045 406 (38.9) 639 (61.1)  
 Cerebral stroke with paralysis    0.126 
  + 28 7 (25.0) 21 (75.0)  
  − 1,061 417 (39.3) 644 (60.7)  
 Ischemic heart disease    0.477 
  + 120 43 (35.8) 77 (64.2)  
  − 980 384 (39.2) 596 (60.8)  
 Chronic renal failure    0.358 
  + 16 8 (50.0) 8 (50.0)  
  − 1,090 422 (38.7) 668 (61.3)  
 Dementia    0.278 
  + 11 6 (54.5) 5 (45.5)  
  − 1,080 416 (38.5) 664 (61.5)  
 Collagen vascular disease    0.285 
  + 81 27 (33.3) 54 (66.7)  
  − 1,001 394 (39.4) 607 (60.6)  
 COPD    0.810 
  + 67 27 (40.3) 40 (59.7)  
  − 1,038 403 (38.8) 635 (61.2)  
 IBS    <0.001 
  + 442 109 (24.7) 333 (75.3)  
     (IBS-C, 136; IBS-M, 197)  
  − 618 306 (49.5) 312 (50.5)  
Medications, n (%) 
 Benzodiazepines    0.239 
  + 301 108 (35.9) 193 (64.1)  
  − 833 331 (39.7) 502 (60.3)  
 Antipsychotics    0.948 
  + 73 28 (38.4) 45 (61.6)  
  − 1,061 411 (38.7) 650 (61.3)  
 Antidepressants    0.724 
  + 84 31 (36.9) 53 (63.1)  
  − 1,050 408 (38.9) 642 (61.1)  
 Antiparkinsonian agents    0.512 
  + 22 10 (45.5) 12 (54.5)  
  − 1,112 429 (38.6) 683 (61.4)  
 Opioids    0.744 
  + 44 16 (36.4) 28 (63.6)  
  − 1,090 423 (38.8) 667 (61.2)  
 CCBs    0.549 
  + 309 124 (40.1) 185 (59.9)  
  − 825 315 (38.2) 510 (61.8)  
 Antiarrhythmic agents    0.873 
  + 40 15 (37.5) 25 (62.5)  
  − 1,094 424 (38.8) 670 (61.2)  
 Diuretics    0.400 
  + 26 8 (30.8) 18 (69.2)  
  − 1,108 431 (38.9) 677 (61.1)  
 NSAIDs    0.111 
  + 126 57 (45.2) 69 (54.8)  
  − 1,008 382 (37.9) 626 (62.1)  

Missing data were noted in the following numbers of patients for each parameter: 31 for BMI, 21 for diabetes, 29 for intracerebral hemorrhage, 45 for cerebral stroke with paralysis, 34 for ischemic heart disease, 28 for chronic renal failure, 43 for dementia, 52 for collagen vascular disease, 29 for COPD, and 74 for IBS.

BMI, body mass index; CCBs, calcium channel blockers; COPD, chronic obstructive pulmonary disease; IBS, irritable bowel syndrome; IQR, interquartile range; NSAIDs, nonsteroidal anti-inflammatory drugs; IBS-C, irritable bowel syndrome constipation; IBS-M, irritable bowel syndrome with mixed bowel habits

Table 4.

Multivariate analysis of the risk factors for persistent constipation symptoms

(Variables)OR (95% CI)p value
Age  0.579 
 <65 years 1.00 (reference)  
 ≥65 years 1.08 (0.81–1.44)  
Sex  0.257 
  Male 1.00 (reference)  
 Female 0.86 (0.66–1.12)  
Comorbidities 
 Diabetes 1.53 (1.05–2.24) 0.028 
 IBS 3.08 (2.34–4.05) <0.001 
(Variables)OR (95% CI)p value
Age  0.579 
 <65 years 1.00 (reference)  
 ≥65 years 1.08 (0.81–1.44)  
Sex  0.257 
  Male 1.00 (reference)  
 Female 0.86 (0.66–1.12)  
Comorbidities 
 Diabetes 1.53 (1.05–2.24) 0.028 
 IBS 3.08 (2.34–4.05) <0.001 

CI, confidence interval; IBS, irritable bowel syndrome; OR, odds ratio.

In the present study, the prevalence of constipation was estimated as 33.3% on the basis of the standardized questionnaire survey using the GSRS. Previous studies reported that the prevalence of constipation in 136 patients undergoing colonoscopy was 10.4–17.5% [20‒22], whereas the complaint ratio for constipation was reported to be 34.8% in the Japanese Comprehensive Survey of Living Conditions [23], and the prevalence of chronic constipation in Japanese individuals was 28.4% [24]. These differences may be attributed to differences in the definition of constipation, sample populations, sample size, and data collection methods among studies.

To date, there is no standard definition of constipation. Although the Rome III criteria are widely used as a definition of functional constipation, Tamura et al. reported that constipation was diagnosed using the Rome III definition in only half of the respondents who self-identified as having constipation [24]. In the present study, we included patients who described themselves as constipation sufferers and did not have mechanical obstruction, such as colorectal cancer, regardless of whether they fulfilled the Rome III diagnostic criteria for chronic constipation.

The GSRS is a disease-specific quality-of-life scale and a self-administered questionnaire that is scored using a 7-point Likert scale to assess the severity of GI symptoms relating to the previous 7 days. The reliability and validity of the GSRS for bowel disease have been well documented [25], and the GSRS has been used to evaluate constipation symptoms in various studies [18, 25‒29]. Thus, it is a useful measure to estimate recent constipation.

Regarding the study population, we included patients who underwent colonoscopy; thus, organic colorectal diseases that cause constipation were excluded. However, the median age in this study was relatively higher, which might also contribute to the higher prevalence of constipation symptoms observed.

In this study, more than 8,600 participants were selected from patients who completed high-quality questionnaires. We revealed that older age, female sex, chronic renal failure, cerebral stroke with paralysis, COPD, ischemic heart disease, diabetes, and multiple medication use were independently associated with constipation symptoms. Among these, aging, female sex, chronic renal failure, cerebral stroke with paralysis, and diabetes have previously been recognized as important risk factors for constipation symptoms [1, 30]. In patients with COPD, constipation is a common symptom [31, 32], and approximately 40% of patients with stable COPD have constipation [33], presumably because they are physically less active than their age-matched individuals [34]. Patients with heart disease often use diuretics for fluid volume control and are instructed to restrict their water intake; the amount of water in the body and gut is decreased, which can promote constipation [35]. Moreover, constipation has been reported to be a risk factor for cardiovascular disease [35] and is associated with a higher risk of all-cause mortality [6]. Various drugs have been reported to induce constipation. Opioids and benzodiazepines are both widely known to cause constipation via μ-opioid receptors and anticholinergic effect, respectively [11, 36]. Constipation is a common adverse effect of many antiparkinsonian medications [37], particularly anticholinergics and dopamine agonists [38].

In this study, IBS and diabetes were identified as risk factors for refractory constipation symptoms. With regard to the physiology of refractory constipation, Mertz et al. identified visceral hypersensitivity, which is typical of IBS in 58%, slow colonic transit in 47%, and overlap of the two in 50% of each group [39]. Visceral afferent alterations associated with IBS can present as enhanced perception of rectal distention in the form of exaggerated accommodation reflexes.

Constipation is one of the most common GI symptoms in patients with diabetes [40]. In one study, nearly 60% of patients with diabetes reported symptoms of constipation [41]. Diabetic neuropathy, defined as peripheral neuropathy of the lower limbs, is significantly associated with constipation [42]. Diabetic neuropathy also leads to decreased colonic transit time and the absence of gastrocolonic reflex. Moreover, both visceral hypersensitivity and impaired accommodation have been shown to be present in diabetic gastroparesis [43]. It has also been reported that patients with diabetes have decreased sphincter tone and increased sensory thresholds for rectal distension, which may contribute to constipation and fecal incontinence [44]. Thus, diabetes increases the risk of refractory constipation due to decreased motility, bowel transit time, and atony of the colon [45].

This study has several strengths. First, the sample size was relatively large, and we included more than 8,600 individuals. Second, we investigated patients who underwent colonoscopy; thus, patients with constipation symptoms caused by colorectal disease were excluded. Third, we used comprehensive questionnaires to obtain detailed data regarding GI symptoms, comorbidities, and medications of the study participants. Finally, only few studies have evaluated risk factors for refractory constipation. However, this study also has some limitations. First, our findings may not be generalizable because this study was conducted at a single hospital and included patients who underwent colonoscopy on the basis of the indication decided by each gastroenterologist (mainly for colon cancer screening). Second, the questionnaire we used did not include all comorbidities, and we could not check for some diseases that may be associated with constipation, such as thyroid and parathyroid diseases. Finally, patients who could not complete the questionnaires for reasons such as severe illness or cognitive decline were excluded, which might have led to a selection bias. Despite these limitations, we believe that this study provides valuable insights on the epidemiology of constipation.

In conclusion, approximately 30% of patients reported constipation symptoms. Female sex, older age, chronic renal failure, cerebral stroke with paralysis, COPD, ischemic heart disease, diabetes, benzodiazepine use, anti-parkinsonian medication use, and opioid use are risk factors for constipation symptoms. Moreover, diabetes and IBS are risk factors for refractory constipation symptoms.

The authors thank the clinical research coordinator, Hisae Kawashiro, for assistance with data collection. We thank Editage (www.editage.com) for English language editing.

The study was conducted in accordance with the principles of the Declaration of Helsinki. Opt-out informed consent protocol was used for this study. This study protocol was reviewed and approved by the Ethics Committee of the National Center for Global Health and Medicine, approval number NCGM-004078. Opt-out informed consent protocol was used for use of participant data for research purposes. This consent procedure was reviewed and approved by the Ethics Committee of the National Center for Global Health and Medicine, approval number NCGM-004078, date of decision January 8, 2021.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

Shiori Komori and Junichi Akiyama designed the study, wrote the initial draft of the manuscript, and collected clinical information and were the principal authors of the manuscript. Junichi Akiyama is an equal first author. Naoko Tatsuno, Erika Yamada, Atsuko Izumi, Mariko Hamada, Kana Seto, Yuriko Nishiie, Keigo Suzuki, Yuya Hisada, Yuki Otake, Yuka Yanai, Hidetaka Okubo, Kazuhiro Watanabe, Naoki Akazawa, Natsuyo Yamamoto, Yasuo Tanaka, Mikio Yanase, Akiko Saito, and Chizu Yokoi performed endoscopies and collected clinical data. Junichi Akiyama, Kazuhiko Yamada, and Akihito Nagahara contributed to the analysis and interpretation of the data and assisted with the preparation of the manuscript. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

The data that support the findings of this study are not publicly available owing to privacy reasons but are available from the corresponding author upon reasonable request.

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