Digestive Disease Week 2011

May 7-10, 2011 Chicago, IL

Study Identifies Long-Term Risk Factors for Onset of Constipation in Elderly Women

Although several factors are thought to predispose an individual to constipation—a problem that affects up to 20% of the general population—researchers have yet to discover precisely why the condition so commonly arises in older women. New data from a team of Australian investigators suggests that giving birth at some point, smoking, and having generally poor health increase the likelihood that a woman will struggle with constipation later in her life. The researchers shared the results of their large, prospective study in a poster presentation during DDW 2011.

The findings constitute a subanalysis of data from the Australian Longitudinal Study on Women's Health, which was initiated in 1996 and surveyed 12,762 community-dwelling women age 70 to 75 years on various health issues. The women were randomly selected from the Australian Health Insurance Database. The survey also solicited information on demographics (eg, nationality, education, marital status, socioeconomic status) and lifestyle issues, such as history of smoking and alcohol consumption, body mass index, number of live births, history of uterine prolapse repair, and cumulative incidence of stressful life events in the previous 3 years. In 2005, approximately 9 years after completing the 1996 survey, 3716 of the women (age range, 79-84 years) agreed to complete a follow-up questionnaire.

In both surveys, respondents were asked, "Have you had constipation in the past 12 months?" The authors define constipation as “persistent difficulty, infrequent, or seemingly incomplete defecation.” According to the investigators, 40.3% (1501/3716) of the women surveyed in 2005 affirmed that they had developed constipation in the intervening 9 years between surveys.

A univariate analysis found significant correlations between new-onset constipation and higher number of live births, higher number of stressful events, lower socioeconomic status, and poorer quality of life across multiple domains, which had been assessed in 1996 using the SF-36, a 36-question short-form health survey. The final multivariate analysis determined that independent risk factors for new-onset constipation consisted of positive marital status (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.39; P = .04); a history of childbirth (OR, 1.07; 95% CI, 1.0-1.14; P = .04), a history of smoking (OR, 1.24; 95% CI, 1.04-1.48; P = .02), a higher score on the pain subscale of the SF-36 (OR, 0.95; 95% CI, 0.92-0.99; P = .01), and a lower score on the general health subscale of the SF-36 (OR, 0.91; 95% CI, 0.87-0.95; P <.000).

The authors noted that constipation commonly occurs among older women living independently in the community setting and degrades health-related quality of life. Previous studies have implicated concurrent disease, certain medications, immobility, and lifestyle factors such as alcohol consumption and lack of fluid and fiber in the diet in the genesis of constipation. This study looked specifically at new-onset constipation and concluded that childbirth issues and poor quality of life are probable long-term risk factors that predispose a woman to constipation late in life.

Linaclotide Significantly Improves Quality of Life and Abdominal Symptoms

An analysis of two phase 3 clinical trials comparing the drug linaclotide with a placebo found that a daily dose of the investigational agent significantly reduced the severity of chronic constipation and related abdominal symptoms, improving patients’ quality of life. Robyn Carson, MPH, Forest Research Institute, Jersey City, NJ, presented data from the study, which was designated a "poster of distinction," at Digestive Disease Week 2011. The authors note that constipation is a common gastrointestinal disorder, affecting approximately 15% of Americans and often associated with severe abdominal discomfort.

Cumulatively, the two multicenter trials enrolled 1272 adult men and women with chronic constipation. Constipation was assessed using modified Rome II criteria, which stipulates fewer than three episodes of defecation weekly for at least 12 consecutive weeks, with no episodes of loose stool and at least 25% of defecations involving two or more of the following symptoms: straining, lumpy or hard stools, incomplete evacuation, and/or a sense of anorectal obstruction.

Participants were randomized to 12 weeks of placebo, linaclotide 133 µg, or linaclotide 266 µg, administered daily via an oral capsule. During a 2-week pretreatment phase, participants completed the self-administered Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire, which includes subscales rating physical discomfort, satisfaction, worries/concern, and psychosocial discomfort; higher scores indicate worse quality of life. The PAC-QOL also asks patients to rate abdominal symptoms on a scale of 1 to 5, with 1 indicating none and 5 denoting very severe.

The investigators stratified patients into three subgroups for a post hoc analysis according to scores ≥2 for abdominal pain (n = 682), abdominal discomfort (n = 868), and bloating (n = 982). Some patients fell into more than one subgroup, with 53.6% of patients experiencing abdominal pain, 68.2% noting discomfort, and 77.2% acknowledging symptoms of bloating. Patients were well balanced between the subgroups, with similar male-to-female ratios and similar proportions of white participants.

At week 12, the PAC-QOL questionnaire was repeated. Responses revealed significant improvement from baseline in overall scores (P <.05) and for all four subscales among patients treated with linaclotide compared with those given placebo. Results were consistent across all three subgroups, regardless of the linaclotide dose used. Among the four subscales, patients receiving placebo had the least improvement in satisfaction scores, which only declined by 0.60. Conversely, this is where patients treated with linaclotide demonstrated the most improvement, with satisfaction scores increasing 1.32 in each group. Although psychosocial discomfort improved significantly with linaclotide 133 µg and 266 µg compared with placebo, the difference between the groups was less stark (-0.74 vs -0.73 vs -0.61, respectively).

In the pain subgroup, PAC-QOL scores declined a median of 0.67 in the placebo group compared with a drop of 1.07 in the linaclotide 133 µg arm (P <.0001) and 1.10 in the linaclotide 266 µg group (P <.0001). For the abdominal subgroup, declines averaged 0.62 in the placebo arm and 1.03 in each linaclotide group (P <.00001 for both comparisons). In the bloating group, the overall mean decline was also significantly greater for patients treated with linaclotide 133 µg and 266 µg than for those taking placebo (-0.97 vs -0.99 vs -0.58, respectively; P <.0001).

The investigators said diarrhea was the most common adverse event with linaclotide therapy. Despite the increased rate of diarrhea, however, findings demonstrate that linaclotide significantly improved quality of life for patients compared with placebo, regardless of the patient’s predominant symptom.