Lower urinary tract symptoms

: a prospective cohort study of risk factors and outcomes in parous middle-aged women

Abstract

Brief Rationale
Lower urinary tract symptoms (LUTS) are defined as storage, voiding and post micturition symptoms. LUTS are highly prevalent (45% to 76%) in women and are associated with lower quality of life. Unfortunately, LUTS are understudied especially in middle aged women as evidence mostly focuses on risk factors or outcomes related to urinary incontinence and neglects other subtypes of LUTS. Direction of association between some risk factor including constipation and physical activity and outcome of LUTS (such as depression and quality of sexual experience) are still not clear due to epidemiological research mostly focusing on cross sectional association. This thesis will focus on disentangling the direction of association between determinants (physical activity and constipation) and outcomes (quality sexual experience and depression) associated with LUTS (by subtypes) in parous middle-aged women by examining the associations prospectively.

Overview of Methods
Avon Longitudinal study of Parents and Children (ALSPAC) is a population-based birth cohort in the southwest of England that have recruited pregnant women in early 90s (1991-1992). These women were followed up over 20 years using multiple questionnaires. Women self-reported LUTS at two timepoints using validated questionnaires British Female Lower Urinary Tract Symptoms questionnaire (2002-2004) and International Consultation on Incontinence Questionnaire on Female LUTS (2011-2012). LUTS were categorized according to International Continence Society definitions as stress urinary incontinence [UI], urgency UI, mixed UI, nocturia, increased daytime frequency, urgency, hesitancy, and intermittency.
In this thesis, two determinants of LUTS were examined prospectively. Women self-reported their physical activity (1999-2001) and were followed up since then for two time points (3 and 11.5 years) were their association with LUTS (2011-2012) was examined. Women who reported constipation symptoms (between 2001-2005) were followed up for approx. 10 years were their association with LUTS (2011-2012) was examined.
This thesis examined two outcomes associated with LUTS (quality sexual experience and depression). Association examined prospectively between women who self-reported LUTS (2002-2004) and reported measures of sexual experience (2012-2014) at two years of follow up. Association between LUTS (2010) and depression (measured by Edinburgh Post Natal Scale) were examined at 10 years of follow up.
All associations were examined using logistic regression and multiple imputation.

Overview of Results
At 3 years of follow up, women (n=4126, mean age 40.5 years; SD 4.5) who performed higher categories of physical activity were prospectively associated with reduced risks of stress UI (adjusted OR=0.51; 95% CI 0.32, 0.80), mixed UI (adjusted OR=0.48; 95% CI 0.24, 0.99), and any type of LUTS (adjusted OR=0.64; 95% CI 0.46, 0.90) compared to women with lower categories of physical activities. At 11.5 years of follow up, women (n=2770, mean age 49.3 years; SD 4.4) who performed higher categories of physical activity were prospectively associated with reduced risks of stress UI (adjusted OR=0.56; 95% CI 0.39, 0.82), mixed UI (adjusted OR=0.34; 95% CI 0.19, 0.63), and any type of LUTS (adjusted OR=0.52; 95% CI 0.37, 0.73) compared to women with lower categories of physical activities.
At 10 years of follow up, women (n=3729, mean age 43.3 years, SD 0.5), who took medication for constipation had increased risks of urinary urgency (adjusted RR=1.35; 95% CI 1.04, 1.95) and hesitancy (adjusted RR=1.72; 95% CI 1.04, 3.01) compared with women who reported not using medication for constipation.
At two years of follow up, women (n=2672, mean age 49.3 years at baseline, SD 0.5) with any LUTS, stress UI, mixed UI and urgency had higher levels of worry and distress related to their sexual desire, orgasm experience and frequency of sex. Stress UI (adjusted OR=1.27; 95% CI 1.04, 1.52), urgency UI (adjusted OR=1.70; 95% CI 1.26, 2.30), and mixed UI (adjusted OR=1.86; 95% CI 1.35, 2.57), were all associated with a lower overall satisfaction of sex life.
Depression in women (n=3226, mean age 43.3years, SD 0.5) at 8 years of follow up was associated with urgency UI (adjusted RR=1.59; 95% CI 1.24, 2.00), mixed UI (aRR=1.70; 95% CI 1.08, 2.65), urgency (aRR=1.51; 95% CI 1.13, 2.01), any LUTS (aRR=1.25; 95% CI 1.10, 1.43).

Conclusion
Physical activity is prospectively associated with reduced risks of LUTS (especially stress UI) in parous middle-aged women. Constipation was prospectively associated with increased risks of LUTS including urgency and hesitancy in parous middle-aged women. LUTS are associated with poorer measures of female sexual dysfunction and higher depression scores. Future studies should focus on causality with LUTS to understand underlying mechanisms and support clinical translation.

Date of Award	24 Jan 2023
Original language	English
Awarding Institution	University of Bristol
Supervisor	Abigail Fraser (Supervisor) & Maria C Magnus (Supervisor)