Objectives

A significant body of knowledge implicates menopausal estrogen levels in the pathogenesis of the common pelvic floor disorders (PFDs). These health conditions substantially decrease quality of life, increase depression, social isolation, caregiver burden, and economic costs to the individuals and society.

Methods

This review summarizes the epidemiology of the individual PFDs with particular attention to the understanding of the relationship between each PFD and menopausal estrogen levels, and the gaps in science and clinical care that affect menopausal women. In addition, we review the epidemiology of recurrent urinary tract infection (rUTI)-a condition experienced frequently and disproportionately by menopausal women and hypothesized to be potentiated by menopausal estrogen levels.

Results

The abundance of estrogen receptors in the urogenital tract explains why the natural reduction of endogenous estrogen, the hallmark of menopause, can cause or potentiate PFDs and rUTIs. A substantial body of epidemiological literature suggests an association between menopause, and PFDs and rUTIs; however, the ability to separate this association from age and other comorbid conditions makes it difficult to draw definitive conclusions on the role of menopause alone in the development and/or progression of PFDs. Similarly, the causative link between the decline in endogenous estrogen levels and the pathogenesis of PFDs and rUTIs has not been well-established.

Conclusions

Innovative human studies, focused on the independent effects of menopausal estrogen levels, uncoupled from tissue and cellular senescence, are needed.

OBJECTIVES: A significant body of knowledge implicates menopausal estrogen levels in the pathogenesis of the common pelvic floor disorders (PFDs). These health conditions substantially decrease quality of life, increase depression, social isolation, caregiver burden, and economic costs to the individuals and society. METHODS: This review summarizes the epidemiology of the individual PFDs with particular attention to the understanding of the relationship between each PFD and menopausal estrogen levels, and the gaps in science and clinical care that affect menopausal women. In addition, we review the epidemiology of recurrent urinary tract infection (rUTI)-a condition experienced frequently and disproportionately by menopausal women and hypothesized to be potentiated by menopausal estrogen levels. RESULTS: The abundance of estrogen receptors in the urogenital tract explains why the natural reduction of endogenous estrogen, the hallmark of menopause, can cause or potentiate PFDs and rUTIs. A substantial body of epidemiological literature suggests an association between menopause, and PFDs and rUTIs; however, the ability to separate this association from age and other comorbid conditions makes it difficult to draw definitive conclusions on the role of menopause alone in the development and/or progression of PFDs. Similarly, the causative link between the decline in endogenous estrogen levels and the pathogenesis of PFDs and rUTIs has not been well-established. CONCLUSIONS: Innovative human studies, focused on the independent effects of menopausal estrogen levels, uncoupled from tissue and cellular senescence, are needed.

Importance

Urinary incontinence, the involuntary loss of urine, is a common health condition that may decrease quality of life. Ten to twenty percent of women and up to 77% of women residing in nursing homes have urinary incontinence, yet only 25% seek or receive treatment.

Observations

This review summarizes the evaluation and therapeutic options for women affected by urinary incontinence. The initial assessment should focus on understanding the effect of incontinence on quality of life, the patient's goals and preferences for treatment, the results of previous treatments, and the presence of concomitant conditions, such as advanced pelvic organ prolapse, that may require referral. Infection and hematuria need to be ruled out. In the absence of urinary infection or serious underlying pathology (such as cancer or serious neurologic disease) associated with urinary incontinence, the clinician should initiate unsupervised pelvic muscle exercises and lifestyle modifications appropriate to the patient to reduce her symptoms. These recommendations can include weight loss, adequate hydration, avoidance of excessive fluids, and regular voiding intervals that reduce urgency incontinence episodes. Urgency incontinence medications, with timely reassessment of symptoms, can be started without extensive evaluation. Specialist treatments for urgency incontinence include onabotulinumtoxinA and percutaneous or implanted neuromodulators. Stress incontinence surgery, the midurethral sling, is associated with symptom improvement in 48% to 90% of women and has low rates of mesh complications (<5%).

Conclusions and relevance

Urinary incontinence is common in women, although few seek care despite many effective treatment options. Clinicians should prioritize urinary incontinence detection, identify and treat modifiable factors, incorporate patient preference into evaluation and treatment, initiate conservative and medical therapy, and refer to specialists when underlying pathology is identified or conservative measures are ineffective.

Authorship and dissemination policies vary across NIH research consortia. We aimed to describe elements of real-life policies in use by eligible U01 clinical research consortia. Principal investigators of eligible, active U01 clinical research projects identified in the NIH Research Portfolio Online Reporting Tools database shared relevant policies. The characteristics of key policy elements, determined a priori, were reviewed and quantified, when appropriate. Twenty one of 81 research projects met search criteria and provided policies. K elements (e.g., in quotations): manuscript proposals reviewed and approved by committee (90%); guidelines for acknowledgements (86%); writing team formation (71%); process for final manuscript review and approval (71%), responsibilities for lead author (67%), guidelines for other types of publications (67%); draft manuscript review and approval (62%); recommendation for number of members per consortium site (57%); and requirement to identify individual contributions in the manuscript (19%). Authorship/dissemination policies for large team science research projects are highly variable. Creation of an NIH policies repository and accompanying toolkit with model language and recommended key elements could improve comprehensiveness, ethical integrity, and efficiency in team science work while reducing burden and cost on newly funded consortia and directing time and resources to scientific endeavors.

Objectives

This study aimed to compare the cost-effectiveness of Botox and anticholinergic (AC) medications for the management of urgency urinary incontinence (UUI).

Methods

Cost and effectiveness data were analyzed from participants in the Anticholinergic versus Botox Comparison randomized trial of daily AC medication versus 100 U of intradetrusor Botox injection. Societal costs included the following: treatment costs, patient costs, and medical and nonmedical utilization during the 6-month trial. Quality-adjusted life-years (QALYs) were calculated based on questionnaire-derived utility measures and annualized based on data collected at baseline through 6 months. We also estimated the average direct costs for each treatment through 9 months - the duration of time when approximately half the Botox participants maintained adequate symptom control.

Results

Data were analyzed on the 231 women who completed a 6-month follow-up in the Anticholinergic versus Botox Comparison trial (119 AC and 112 Botox). The mean reduction in UUI episodes per day was not significantly different per group. The cumulative mean direct costs through the first 6 months also were similar: $1339 for the AC group and $1266 for the Botox group with AC costs exceeding Botox costs after 5 months. Both groups had considerable QALY gains. Annualizing the 6-month trial results to a 12-month measure, the AC and Botox groups averaged 0.702 and 0.707 QALYs, respectively. Estimates through 9 months favored Botox, showing that AC participants incurred a higher cost per month of adequate symptoms control ($305) compared with Botox participants ($207).

Conclusions

Botox and AC medications have similar costs and effectiveness in the first 6 months of UUI treatment. If costs and outcomes are considered through 9 months, Botox may have significantly lower costs but similar UUI symptom control as AC.

AIMS: Prior research on lower urinary tract symptoms (LUTS) has focused on the treatment and management of these conditions with scant attention to prevention. The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium was formed to address the complexities of preventing LUTS and promoting bladder health. METHODS: Herein, we describe challenges faced and strategies used to develop the PLUS Research Consortium into an engaged and productive transdisciplinary scientific team. We apply four previously defined team science phases (development, conceptualization, implementation, and translation) to frame our progress. RESULTS: Strategies to progress through the development phase included the generation of a shared mission, and valuing of other disciplinary perspectives. The conceptualization phase included generating a shared language and developing a team transdisciplinary orientation. During the implementation phase, the group developed roles and procedures and focused on conflict management. The translation phase includes continued refinement of the mission and goals, implementation of research protocols, and robust dissemination of the scientific work products related to bladder health. CONCLUSION: A diverse group has matured into a productive transdisciplinary team science consortium. Achieving this outcome required dedicated effort for each member to engage in activities that often required more time than single discipline research activities. Provision of the necessary time and tools has fostered a transdisciplinary team science culture and rich research agenda that reflects the complexity of the health issue to be addressed. Our experience may be useful for others embarking on team science projects.

Objective

To longitudinally assess the effect of native tissue vaginal apical prolapse repair with anti-incontinence surgery on quality of life, sexual function, and body image between uterosacral and sacrospinous suspensions.

Methods

A planned secondary analysis was performed on 374 women enrolled in a randomized trial of the two types of native tissue repair for apical prolapse. Condition-specific and generic quality of life, sexual function, overall and de novo dyspareunia, and body image were assessed using validated instruments at baseline; 6, 12, and 24 months postoperatively; and changes from baseline were assessed and compared between surgical groups. General linear mixed models were used for comparisons and clinically significant differences were assessed using minimum important differences.

Results

Of the women randomized, 82% had outcomes available at 2 years. Overall, clinically and statistically significant improvements in generic and condition-specific quality of life and sexual function were observed after surgery. Dyspareunia rates decreased from 25% to 16% by 24 months with only 3% of all women undergoing treatment. De novo dyspareunia occurred in 5% and 10% by 12 and 24 months, respectively. Body image scores also significantly improved from baseline. There were no clinically meaningful or statistically significant differences between groups for any of these outcomes (all P>.05).

Conclusion

Native tissue vaginal prolapse surgery results in statistically and clinically significant improvements in quality of life, sexual function, and body image at 24 months with no significant differences between uterosacral and sacrospinous suspensions. One in 10 women experience de novo dyspareunia but few requested treatment.

Clinical trial registration

ClinicalTrials.gov, www.clinicaltrials.gov, NCT00597935.

The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples. To our knowledge, we also contribute some of the first evidence regarding the impacts of multiple swabs taken at one time point. Vaginal samples have relatively low biomass, so the ability to collect multiple swabs from a unique participant at a single time would greatly improve the replicability and data available for future studies. This will hopefully lay the groundwork to gain a more complete and accurate understanding of the vaginal microbiome.

Purpose

To determine the best predictor of the mid urethral sling outcome we calculated the AUC of ROC curves of preoperative parameters, including Valsalva leak point pressure, maximum urethral closure pressure, urinary NTx (N-telopeptide of crosslinked type I collagen) and plasma vitamin D values (D2, D3 and D2 plus D3).

Materials and methods

This was an ancillary study of TOMUS (Trial of Mid-urethral Slings) and the ValUE (Value of Urodynamics Evaluation) trial in which subjects underwent mid urethral sling surgery for stress urinary incontinence. Valsalva leak point pressure and maximum urethral closure pressure were measured in 427 subjects, whereas NTx, vitamin D2, vitamin D3 and vitamin D2 plus D3 levels were obtained from 150, 116, 115 and 116 subjects respectively. Outcome success was defined using identical outcome (subjective and objective) variables for all subjects. ROC curves with corresponding AUC values were compared.

Results

TOMUS and ValUE subjects were significantly different in age, body mass index, UDI (Urogenital Distress Inventory) scores. TOMUS subjects had a lower surgical success rate compared to ValUE subjects (66.3% vs 76.0%, p = 0.03). The AUC values of Valsalva leak point pressure, maximum urethral closure pressure, NTx, and vitamins D2, D3 and D2 plus D3 were 0.542, 0.561, 0.702, 0.627, 0.645 and 0.640, respectively. The AUC of NTx was significantly higher than the AUCs of Valsalva leak point pressure and maximum urethral closure pressure (p = 0.02 and 0.03, respectively).

Conclusions

Urinary NTx was the best predictor of the mid urethral sling outcome. This test is not only noninvasive, it is also modifiable. Finding ideal modifiable risk factors prior to mid urethral sling surgery should be subject to future investigations.

Standardized conditions for collection, preservation and storage of urine for microbiome research have not been established. We aimed to identify the effects of the use of preservative AssayAssure® (AA), and the effects of storage time and temperatures on reproducibility of urine microbiome results. We sequenced the V3-4 segment of the 16S rRNA gene to characterize the bacterial community in the urine of a cohort of women. Each woman provided a single voided urine sample, which was divided into aliquots and stored with and without AA, at three different temperatures (room temperature [RT], 4 °C, or -20 °C), and for various time periods up to 4 days. There were significant microbiome differences in urine specimens stored with and without AA at all temperatures, but the most significant differences were observed in alpha diversity (estimated number of taxa) at RT. Specimens preserved at 4 °C and -20 °C for up to 4 days with or without AA had no significant alpha diversity differences. However, significant alpha diversity differences were observed in samples stored without AA at RT. Generally, there was greater microbiome preservation with AA than without AA at all time points and temperatures, although not all results were statistically significant. Addition of AA preservative, shorter storage times, and colder temperatures are most favorable for urinary microbiome reproducibility.