The UCSF Women's Continence Center providers are leaders in urinary incontinence and pelvic floor dysfunction research. Our clinical research team has completed several studies to estimate the prevalence of and risk factors for female urinary incontinence. Nearly 50% of community-dwelling women over 60 years of age are incontinent with about 15% having daily incontinence, making incontinence far more common than most chronic medical illnesses. To identify potential strategies to prevent and/or treat incontinence, we have focused our investigations on modifiable or preventable risk factors, including obesity, childbirth, hysterectomy, hormone therapy and diabetes. We have also used these insights to develop novel treatments for female incontinence.
Some of the highlights of our research activities are provided below:
• Urinary Incontinence Linked To Falls And Fractures
• Hysterectomy Surgery Linked To Risk Of Urinary Incontinence In Later Life
• Estrogen Therapy May Contribute To Urinary Incontinence
• Weight Reduction to Treat Urinary Incontinence In Obese Women
• Low-Intensity Behavioral Therapy Improves Incontinence
• Reproductive Risk Factors For Urinary Incontinence
• Diabetes: Lower Urinary Tract Dysfunction and Infections
• Molecular and Genetic Mechanisms of Stress Incontinence
• A SimpleTest to Diagnose Urinary Incontinence in Women
Nearly 35% of women over the age of 40 have urinary incontinence, which is associated with increased social isolation, falls, fractures, and admissions to specialized nursing units. Women report that it is the discomfort, embarrassment and bothersomeness of urinary incontinence that prompts them to seek treatment.
BRinging simple urge Incontinence DiaGnosis & treatment to providerS (BRIDGES) is an exciting new research study looking at six hundred and thirty-six women diagnosed with urge urinary incontinence (UUI) by a three-item self-administered questionnaire (3IQ) will be randomized to 12 weeks of fesoterodine 4 mg daily, fesoterodine 8 mg daily or matching placebo. The study will take place at up to 14 clinical sites in the US. All participants who complete the 12-week randomized trial will be offered open-label fesoterodine for an additional 9 months.
In a recent study by the Diabetes Prevention Program (DPP), women with pre-diabetes (also called impaired glucose tolerance) prevented diabetes and urinary incontinence (leakage of urine) by losing weight and increasing exercise. The 1,987 women recruited for the study had an average age of 50 years (range 24 to 84) and were split into groups: (1) intensive lifestyle intervention, or ILS, (2) medication and (3) placebo. The ILS group had a modest goal of at least a 7% weight loss and 150 minutes of exercise per week. The participants were followed for an average of 2.8 years.
Jeanette S. Brown, M.D. is a principle investigator for the Incontinence Study. Dr. Brown indicated that diabetes has been associated with a 60% increased risk of urinary incontinence.
"Less incontinence will be a powerful motivator for the women who have pre-diabetes to loose weight and increase exercise to prevent diabetes and incontinence," said Dr. Brown. "Women may experience incontinence with intense exercise; however the key to success here is to exercise at a moderate level and consistently each week to achieve weight loss, which helps improve incontinence.”
On going research among women with type 2 diabetes is also incorporating weight loss and exercise to determine if type 2 diabetes can be improved and complications prevented like heart disease, eye, kidney, and nerve damage. In addition, urinary incontinence measures are also included. Dr. Brown is quite optimistic that the same results of improved and prevented incontinence will occur among women with type 2 diabetes.
These exciting new studies are funded by the National Institute of Diabetes, Digestive & Kidney Diseases. http://www.niddk.nih.gov/
Please click here to view the scientific abstract, which was presented at the American Urological Association 2004 Annual Meeting.
Urinary incontinence is a common problem among middle aged and older women, producing substantial distress and diminished quality of life, as well as dramatic limitations in daily functioning. Overweight women are at significantly greater risk of urinary incontinence. Initial data from preliminary studies suggest that weight reduction for overweight and obese women improves urinary incontinence. Thus, weight loss represents a promising new approach to urinary incontinence treatment that also produces many health improvements in addition to improved continence.
PRIDE (Program to Reduce Incontinence by Diet and Exercise) is an exciting new research study, supported by the National Institutes of Health (NIH), to learn more about the effects of weight loss on urinary incontinence. About 330 overweight and obese women with urinary incontinence are currently being randomized to either a 6-month lifestyle & behavioral change weight loss program or to a structured educational program with no weight reduction intervention. At the end of the 6-month program, women in the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow us to determine if long-term weight reduction will produce continued improvement in urinary incontinence. Recruitment for PRIDE commenced on July 1, 2004.
Urinary incontinence, falls, and fractures are common health problems in later life, particularly in older women. The symptoms associated with urinary incontinence such as frequent urination, a sense of urgency to urinate, or rushing to the bathroom to avoid incontinent episodes may increase the risk of falls and subsequent fractures. Dr. Jeanette Brown, director of the UCSF Women's Continence Center conducted a study to research this relationship.
Over 6,000 women participated in the study. The study found that weekly or more frequent urge incontinence independently increased the risk of falls by 26% and the risk of fractures by 34%. Women with daily urge incontinence are at greatest risk. Stress incontinence was not associated with risk of falls or fractures.
Thus, the diagnosis and treatment of urge incontinence may be an effective way to reduce the risk of falls and fractures among women. Behavioral and drug therapies have shown that treatment of urge incontinence also leads to less frequent and urgent trips to the bathroom, therefore decreasing risk of falls and fractures. Environmental modifications such as a bedside commode for women with frequent nighttime incontinence may also decrease the risk of falls and fractures.
More than 600,000 women have hysterectomies each year in the United States, making this the second most common major surgical procedure (after Cesarean section). By age 60, about 40% of women in the United States have had a hysterectomy. Nearly 90% of hysterectomies are done for benign symptomatic disorders (such as uterine fibroids, vaginal bleeding, pelvic pain, and pelvic organ prolapse).
Hysterectomy may lead to damage to the pelvic nerves or pelvic support structures that increases risk of urinary incontinence. Dr. Jeanette Brown, Director of the UCSF Women's Continence Center performed a meta-analysis (a systematic review of the literature) to determine whether urinary incontinence might be a long-term consequence of hysterectomy.
Dr. Brown analyzed the results of 12 other studies that had been done on this topic. The data indicated that the odds of developing urinary incontinence after hysterectomy were about 40% higher than for women who had not undergone a hysterectomy. However, since urinary incontinence may not develop for many years after hysterectomy surgery, the study data were analyzed by age of participant. After age 60, the odds of developing urinary incontinence were about 60% higher for women who had had a hysterectomy. These findings indicate that it is important for health care providers to counsel their patients considering hysterectomy about the long-term risk of urinary incontinence that may result from this surgery.
Dr. Jeanette Brown, Director of the UCSF Women's Continence Center has been involved with a study to determine if postmenopausal hormone therapy improves the severity of urinary incontinence. Questions about incontinence and voiding frequency were added to an ongoing, randomized, blinded clinical trial of the effect of hormone therapy among over 2,700 postmenopausal women under 80 years old. Study participants were randomly assigned to estrogen therapy or placebo (sugar pill) and followed for an average of 4.1 years. Severity of incontinence was classified as improved (if there was a decrease of at least two episodes per week), unchanged, and worsened (if there was an increase of at least two episodes per week).
The study found that incontinence improved in more women taking the placebo than those taking the estrogen therapy. Additionally, for women whose condition worsened, those taking the estrogen actually experienced more problems than those taking the placebo. Thus, the results indicated that daily oral estrogen therapy was associated with worsening urinary incontinence in older postmenopausal women with weekly incontinence and that estrogen therapy should not be a recommended treatment.
Urinary incontinence is a common problem among middle aged and older women and overweight women are at significantly greater risk of urinary incontinence. Dr. Leslee Subak, one of the UCSF Women's Continence Center faculty members, conducted a study to evaluate the effect weight reduction has on incontinence in moderately obese women. The study included 10 women who were moderately overweight and had over 10 incontinent episodes per week. The study demonstrated an association between weight reduction and improved urinary incontinence. Women participating in the study who achieved a weight loss of at least than 5% had greater than 50% reduction in incontinence frequency, compared to the women who had less weight loss. In a second study, 42 overweight and obese women with incontinence were randomized to either a 3-month liquid diet program or no intervention. Women in the diet program lost an average of 31 pounds over three months and their frequency of incontinence episodes was reduced 60% compared to a 4% improvement among women receiving no intervention. Incontinence appeared to improve when women lost as little as 5% of their baseline weight, a reasonable treatment goal for many overweight and obese women. Thus, modest weight reduction may be a feasible and effective treatment option for incontinence and should be considered as part of non-surgical therapy for incontinence. Moreover, focusing on weight loss for these women will likely improve their general health, as weight losses of 5-10% are known to improve the control of high blood pressure, diabetes, and high cholesterol, reduce the risk of developing type 2 diabetes, and produce marked improvements in mood and quality of life. Further research is proposed with additional women to evaluate the effect of weight reduction on incontinence symptoms and to identify patient and disease characteristics that predict improvement in urinary incontinence following weight loss.
Low-Intensity Behavioral Therapy Improves Incontinence
Many treatments are commonly used for urinary incontinence, including behavioral therapy, medications and surgery. Behavioral therapies, including voiding at scheduled times (bladder training), pelvic muscle exercises ("Kegel" exercises) and biofeedback therapy, are often recommended as the initial treatment for incontinence. Dr. Subak and colleagues at Kaiser Permanente Medical Center conducted a study to evaluate a low-intensity behavioral intervention that can be initiated effectively and easily by primary care healthcare providers. 152 women over 55 years of age with incontinence were randomized to participate in 6 weeks of instruction on bladder training and written information on bladder function and Kegel exercises or no intervention. Women in the behavioral treatment program had a significant improvement in incontinence compared to the women without treatment. This low-intensity behavioral therapy intervention for urinary incontinence was effective and should be considered as a first-line treatment for urinary incontinence in older women.
Drs. David Thom, Steven Van den Eden, Jeanette Brown and Leslee Subak are conducting a study to determine the independent associations between specific childbirth variables, hysterectomy, and hormone use, and subsequent urinary incontinence and pelvic floor problems. Approximately 2,100 women will be surveyed.
From preliminary data, 73% of women have reported at least one episode of incontinence in the past 12 months or ever having been treated for incontinence. The analysis of the results found a positive association between urinary incontinence and body mass, birthing a child vaginally, and the use of estrogen. An association was also found between exposure to oxytocin during labor and incontinence in later life. At the completion of the study, more extensive analysis will be performed on these relationships.
Diabetes, lower urinary tract dysfunction (LUTD) and urinary tract infections (UTI) are common health problems in older women . Although it has been suggested that these health problems are more common in women with diabetes, there has been limited research in this area. In particular, there has been limited research on specific aspects of diabetes severity that may contribute to the development or severity of lower urinary tract dysfunction and infection. In collaborative projects over the next five years with the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK), Dr. Brown will collect data from three large ongoing diabetes studies to determine risk factors, mechanisms, and possible interventions to prevent or decrease incontinence severity.
Pregnancy, vaginal delivery, birth trauma and menopasue are risks factor for developing stress urinary incontinence in women. To better understand why these events are associated with incontinence, Drs. Tom Lue and Ching Lin developed a mouse model to study stress incontinence. They have studied the effect of pregnancy, delivery, birth trauma, menopause and aging on the structure and function of the rat continence mechanism. They have observed that nerves, blood vessels and muscled of the bladder and urethra are altered in rats with stress urinary incontinence. Future research will focus on the molecular mechanism involved in the developing stress urinary incontinence. They are exploring alterations in gene and protein expression that occur following pregnancy/delivery, birth trauma, and menopause and seek to identify genes that are associated with female stress urinary incontinence.
Drs. Lue, Lin and Emil Tannagho have been exploring the use of a new material to treat stress incontinence. Their research suggests that this new material, organ-specific acellular matrix, can facilitate regeneration of the blood vessel, muscle and nerve in the urethra and thus restores continence. They are actively investigating the use of this new treatment in a rat animal model and plan to continue work on treating women with stress incontinence.
Brown JS, Kanaya AM, Barrett-Connor E, Nyberg LM, Kusek JW, Orchard TJ, Vittinghoff E for the Diabetes Prevention Program (DPP) Research Group. “Lifestyle Intervention Reduces Prevalence of Urinary Incontinence” (abstract) Presented at the American Urological Association 2004 Annual Meeting, San Francisco, May 8-12, 2004.
Jeanette S. Brown*, Alka Kanaya, Elizabeth Barrett-Connor, Leroy M. Nyberg, John W. Kusek, Trevor J. Orchard, Yong Ma, Eric Vittinghoff; University of California, San Francisco and for the Diabetes Prevention Program (DPP) Research Group, Rockville, Maryland
Introduction: Urinary incontinence (UI) affects over 25% of older women, and diabetes has been associated with a 60% increased risk of UI. UI improves with weight loss, but may be adversely affected by exercise. We hypothesized that the intensive lifestyle intervention in the Diabetes Prevention Program (DPP) would decrease UI prevalence among women with impaired glucose tolerance (IGT), primarily through its short-term effects on weight.
Methods: At the DPP end-of-study visit, women completed a validated self-reported questionnaire to determine the prevalence and frequency of UI. Prevalence of = weekly UI was compared across three treatment groups (lifestyle, metformin, and placebo) using logistic regression. Nested logistic models were used to examine mediation.
Results: At the end-of-study visit, 1987 women completed the UI questionnaire. There was no difference in baseline demographic, reproductive, and medical characteristics of these women across the treatment groups. Mean age at entry was 50 yrs. (SD 10, range 25-84). Overall, 43.9% of women reported > weekly UI, with 14.1% having daily UI. UI prevalence was significantly affected by treatment (p = 0.008): lifestyle 38.7% vs. Placebo 45.8%. Metformin had no effect on UI. We found no significant subgroup effects. Mediators of the lifestyle intervention effect on UI included increased physical activity, weight loss, and reduced incident diabetes.. However, changes in weight and physical activity only accounted for 24% of the protective effect of the lifestyle intervention on UI, and differential diabetes incidence among the treatment groups appeared to play almost no mediating role.
Conclusions: Prevalence of weekly UI was substantially decreased by the DPP intensive lifestyle intervention. Increased exercise did not appear to have an adverse effect on UI. Other potential mediators of the intervention effect will be examined. Less urinary incontinence may be a powerful motivator for women with IGT to choose lifestyle modification to prevent diabetes. The same UI questions are asked in the ongoing follow-up of the DPP cohort in the DPP-Outcomes Study, and will enable us to examine longer-term effects.