The association of depression with lower urinary tract symptoms: data from the National Health and Nutrition Examination Survey, 2005–2008

Introduction

Lower urinary tract symptoms (LUTS) are common in aging men, with approximately 80.0% of men experiencing at least one urinary symptom by the age of 80 (Wei, Calhoun & Jacobsen, 2005). Treatment of LUTS is a substantial financial burden on the United States healthcare system (Hu et al., 2004). Moreover, LUTS has been found to have a significant negative impact on quality of life in several studies (Coyne et al., 2009; Robertson et al., 2007). Although LUTS is highly prevalent, poses an economic burden, and adversely affects quality of life, few treatment modalities for it exist, and although pharmacologic interventions are considered first-line therapy, Cindolo et al. (2015) reported that only 29.0% of patients use these drugs for 1 year, indicating that adherence to these medications is poor.

Most medications for LUTS focus on solving bladder outlet obstruction resulting from hypertrophy of the prostate. However, there are multifactorial causes of LUTS development, and the often reported ineffectiveness of pharmacologic therapies implies that the cause of LUTS is not always prostate-centric (Kakizaki & Koyanagi, 2000). Indeed, a variety of factors have been reported to be associated with the development and progression of LUTS, including age-dependent structural and functional changes in the bladder and urethra, neurological and hormonal changes, diabetes and obesity, psychological and behavioral changes, and alterations in sleep patterns (Kakizaki & Koyanagi, 2000; Helf et al., 2011; Helf et al., 2012; Tam, Helfand & Erickson, 2017).

Several studies have reported on associations between psychological factors and LUTS. Most studies have focused on depression, which has been widely reported to be associated with LUTS (Coyne et al., 2009; Hakkinen et al., 2008; Laumann et al., 2008; Steers, Litman & Rosen, 2008; Fitzgerald et al., 2007). A few have reported an association between sleep disorders and the development of nocturia. A recent study reported a relationship between sleep disorders and LUTS (Fantus et al., 2018).

To our knowledge, this is the first study to thoroughly investigate factors associated with LUTS from the National Health and Nutrition Examination Survey (NHANES), 2007–2008, which is a large, cross-sectional dataset that is representative of the United States population. We investigated demographic differences and psychological factors, such as depression and sleep disorders, in patients with LUTS in order to identify dominant factors associated with LUTS.

Materials & Methods

Results

Discussion

In our study, daytime LUTS and clinical LUTS were significantly associated with age, employment status, and depression. We also found that men with greater depression scores were more likely to have LUTS, with the exception of those in the most severe depression group. We modeled LUTS evaluated its association with severity of depression. While treatment of LUTS in men has been mainly prostate-centric, our study suggests that multiple factors might be involved in the development of LUTS and that this urologic manifestation could be considered a socioeconomic and systemic disease with psychological etiologies. We are planning future studies to determine whether reducing levels of depression by medication would help symptoms of LUTS. This future study would highlight the role of psychological treatment in LUTS if depression exists.

An association between depression and LUTS has been reported in several cross-sectional studies (Coyne et al., 2009; Fitzgerald et al., 2007; Asplund et al., 2004; Wong et al., 2010). Furthermore, a prospective study by Hakkinen et al. (2008) reported that depressive symptoms increase the incidence of nocturia. This relationship can be explained psychologically. LUTS reduces quality of life (Coyne et al., 2009; Robertson et al., 2007) and can result in embarrassment, social anxiety, and demoralization (Breyer et al., 2014). Indeed, men with LUTS report decreased self-esteem since they perceive it as a weakness and part of the aging process (Wong et al., 2010). Nocturia may cause daytime drowsiness and decrease concentration and activity levels, all of which could lead to an increased risk for the development and progression of depression.

Several molecular pathogeneses of an association between depression and LUTS have been proposed. Steers et al. postulated that a defect in serotonin synthesis is associated with the development of depression and abnormal voiding dysfunction. Increased adrenergic tone and the hypothalamic-pituitary axis have been proposed as a mediator of depression in LUTS (Laumann et al., 2008; Steers, Litman & Rosen, 2008). Furthermore, Klausner & Steers (2004) suggested that stress-induced depression activates the corticotropin-releasing factor pathway, which functions as a mediator of emotional influences on bladder function. Moreover, inflammation represents a common mechanism in the pathogenesis of major depression and LUTS (Miller, Maletic & Raison, 2009; Johnson et al., 2010). Patients with depression frequently exhibit increased levels of C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 (Miller, Maletic & Raison, 2009). Our results showed that depressed patients (PHQ-9 score ≥ 10) had higher levels of C-reactive protein (0.62 ± 1.23 mg/dL) than those without (0.40 ± 0.77 mg/dL); however, the difference was not statistically significant.

Contrary to a previous study that reported that men with greater depression scores were more likely to have LUTS (Breyer et al., 2014), our results showed that patients with the greatest depression scores were less likely to have LUTS than those with moderate depression. Breyer et al. (2014) defined the depression group as those with a PHQ-9 score ≥10. In our study, we further divided the depression group into a moderate group and a moderately severe to severe group. The moderate depression group showed higher odds with clinical LUTS (OR = 5.89, 95% CI [3.44–10.11]) and individual symptoms of LUTS, except incomplete emptying, compared to the moderately severe to severe depression group (OR = 3.74, 95% CI [1.75–8.00]). This implies that clinical LUTS may not be proportionally associated with the severity of depression. Although its pathogenesis is unclear, the aforementioned molecular pathogenesis might not be feasibly true since if molecular pathways are involved in mediating depression and LUTS, both severity levels of depression and LUTS should be proportionally elevated. This finding implies the existence of unaccounted pathogeneses that mediates LUTS.

Our results showed that there was no significant association between sleep disorders and daytime or clinical LUTS. However, a recent study reported that men with sleep disorders are significantly more likely to report both nocturia and daytime LUTS (Fantus et al., 2018). Sleep disorders increase the risk of daytime urinary symptoms including voiding and storage symptoms (Helf et al., 2011), whereas the improvement of LUTS has been associated with an improvement in sleep disorders (Helf et al., 2012). Although the proportion of men with sleep disorders was higher in the group with daytime and clinical LUTS, the sleep disorder itself might not be a factor associated with LUTS, rather a secondary feature of LUTS.

A cross-sectional study in six European countries reported that men with overactive bladder symptoms were more likely than women to report that overactive bladder symptoms had an impact on their daily work life (Irwin et al., 2006). Over 21.0% of the study population reported being worried about an interruption of meetings owing to urinary frequency, and 3.0% of the population changed or quit their jobs due to bladder control problems. This study reported a negative association of LUTS on employment issues, which is similar to our results. To our knowledge, our study is the first to report a negative association for LUTS on employment in a United States population.

This study has several limitations. First, due to the limitations of its cross-sectional design, a causal relationship could not be established. Second, measurement of the severity of LUTS was limited due to the lack of data of the International Prostate Symptom Score (IPSS). A comparison between the IPSS and PHQ-9 score may have provided more detailed information regarding the association between LUTS and depression. Third, medical conditions were assessed based on self-reporting. Therefore, some of the information for the comorbid conditions might not be accurate. Fourth, treatments for the depression and sleep disorders were not documented. Fifth, due to the retrospective analysis, the adequacy of the sample size could not be checked. Sixth, we did not consider sampling weights since our purpose was to study relations in a large community sample, rather than estimate national prevalence rates. Therefore, we did not use sampling weights in our calculations (Farmer et al., 1988). Seventh, we considered that the size of the study population was large enough to represent the US population and the values were not skewed in clinical perspective; therefore, we used geometric means and SDs and t-tests in univariable analysis. Finally, voiding diaries were not included in the NHANES datasets, which deferred the differential diagnosis of nocturnal polyuria and other causes of nocturia.

Conclusions

Our study revealed significant associations for depression and employment statuswith clinical and daytime LUTS. The cause of LUTS is multifactorial, and psychological factors seem to be significantly associated therewith. Therefore, patients presenting with LUTS should be screened for multi-factorial etiologies using a psychological evaluation for a successful multidisciplinary treatment approach.