Five distinct clusters of women with LUTS were identified using 185 variables. Properties of the five clusters named W1-W5 are shown (Figure 1). Each column represents one of five clusters. Radar plots in the first row illustrate urinary symptoms measured by the LUTS Tool, the second row illustrates demographics, clinical measurements and non-urinary PROs, the third row presents categorical data on comorbidities and anomalies identified during the physical exam, and the fourth row shows intake and voiding pattern variables collected in bladder diaries. Radar plots represent the mean values of the variables across the members of each cluster. None of the clusters could be characterized by a single symptom, but rather by a combination of symptoms with various levels of severity. Women in all five clusters reported higher than normal frequency of voiding (with the highest frequency in W3 and W5). Women in all clusters except W1 reported urinary urgency and some level of incontinence. Women in cluster W1 (n=77) did not report incontinence, but had post-void dribbling, trickling, straining, and symptoms of incomplete bladder emptying. They were younger than average across the cohort, had lower than average weight, number of pregnancies, and vaginal births, and fewer comorbidities and abnormal physical exam findings. Women in cluster W2 (n=64) reported mild urinary symptoms including mild urinary incontinence. They were characterized by the presence of clinically significant pelvic organ prolapse (high values of POP-Q point Ba). They were on average older (66 vs. 53 years old), with more pregnancies (2.9 vs 1.8) and vaginal births (1.47 vs 0.92) than women in cluster W1. They also had the highest post void residual (75 mL) across the clusters. Women in cluster W3 (n=144) reported high urinary frequency, urgency, and urgency urinary incontinence. They had a greater weight, larger waist circumference, and higher functional comorbidity index (FCI) than women in W1, W2, and W4. They reported the most “urgency with fear of leakage” across the clusters, but did not report any substantial post voiding symptoms. Women in cluster W4 (n=95) reported stress incontinence, as well as urgency urinary incontinence, and some post void urinary incontinence. They were younger (mean 51 yo), healthier (FCI =1.24), and more physically active (PROMIS Physical Functioning T-score=53.2) than others in the cohort. Women in W5 (n=165) reported all LUTS at uniformly high levels. For 27 out of 30 urinary symptoms, they reported the highest levels across all five clusters. They demonstrated the greatest mean weight (87.6 Kg), were the least physically active (PROMIS Physical Functioning T-score=42.2), had more comorbidities (FCI=3.64) and pregnancies (3.07) than the rest of the cohort. Pairwise comparison of the clusters demonstrated that multiple variables were significantly different (52% on average across pairs of clusters; range from 27% for W1 vs W2 to 83% for W2 vs W5).
Figure 2 presents the volcano plots comparing abundances of 276 proteins in serum samples of women with LUTS versus controls. Fig 2a compares the abundances for all 230 women with LUTS to 30 controls, while Figs 2b-2f provide similar comparisons for the members of the identified clusters W1-W5 for whom proteomics assays were performed (n1=37, n2=38, n3=53, n4=42, n5=60). Multiple differentially abundant proteins are observed in the serum samples of women with LUTS versus controls both overall and between each cluster and controls. While some of these proteins have been shown [3] to be associated with LUTS, e.g. TNF, IL-10, MCP, and TGF, the remainder are novel.