Serotonin (5-hydroxytryptamine [5-HT]), synthesized from L-tryptophan mainly in the gut and the brainstem, is one of the important neurotransmitters associated with micturition. 5-HT receptors, which are divided into seven families (5-HT1–7), contribute to sensorimotor function in the lower urinary tract, such as the detrusor and the external urethral sphincter, and to the central pathway activities in the micturition reflex. Some types of 5-HT receptors are expressed in the urothelium and may be involved in the visceral sensation of the bladder. This implies that urinary 5-HT might be related to the pathophysiology of OAB. Because 5-HT levels in urine are positively correlated with serum levels, we hypothesized that serum 5-HT levels may be related to symptoms of OAB. We aimed to investigate the relationship between serum 5-HT levels and OAB in a community-dwelling population (n = 1,024; 394 men and 630 women).
Of 1,024 participants, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and depressive tendency. There was a significant correlation between the log serum 5-HT levels and total overactive bladder symptom score (OABSS) (r =-0.159, P <0.001; Figure 1) Participants’ serum 5-HT levels in the OAB group was significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P <0.001). Multivariable analysis showed that age and log serum 5-HT level (OR; 0.25, 95% CI; 0.10–0.68, P = 0.006) were independently associated with OAB. Our results indicated that lower serum 5-HT levels could independently be associated with the presence of OAB.
Possible mechanisms underlying our results are as follows. 1) Lower serum 5-HT levels might reflect lower 5-HT activity in CSF and less inhibition of the micturition reflex in the CNS, which might worsen OAB symptoms. 2) Subjects with OAB who have a lower serum 5-HT level might have bladder hypersensitivity caused by urinary adenosine triphosphate (ATP) in the bladder. However, the exact roles of 5-HT receptors and the interaction of each subtype of receptors in the micturition reflex remain unknown and few studies have investigated the exact roles of 5-HT and its receptors in the human urothelium. Further study is warranted to clarify a possible causal relationship between OAB and serum 5-HT levels.
Written by: Teppei Okamoto, MD, and Shingo Hatakeyama, MD, PhD, Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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