FEMALE UROLOGY

Incidence of urinary incontinence in postmenopausal women treated with raloxifene or estrogen
Goldstein SR, Johnson S, Watts NB, Ciaccia AV, Elmerick D, Muram D
From the Department of OB/GYN, New York University Medical Center, New York, NY; University of Iowa College of Medicine, Iowa City, IA; Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH; and Women’s Health and Reproductive Medicine, Lilly Research Laboratories, Indianapolis, IN, USA
Menopause. 2005; 12: 160-164

• Objective: Determine the effect of raloxifene or estrogen, as compared with placebo, on the reporting of urinary incontinence in postmenopausal women participating in an osteoporosis prevention trial.
• Design: The current analysis is based on adverse event data that were collected as part of a double-blind, randomized, placebo-controlled trial designed to assess the efficacy and safety of raloxifene for osteoporosis prevention in postmenopausal women. Women were 40 to 60 years of age at study entry and had a prior hysterectomy. A total of 619 women were randomized to placebo, raloxifene 60 or 150 mg/d, or conjugated equine estrogen 0.625 mg/d and followed for up to 3 years. Urinary incontinence was self-reported and rated by participants as “mild”, “moderate” or “severe”.
• Results: The prevalence of urinary incontinence as reported by patients at baseline was similar across treatment groups (3% to 6%, P = 0.46). During 3 years of follow-up, new or worsening urinary incontinence was reported with the following frequency: placebo (1.3%), raloxifene 60 mg/d (0.7%), raloxifene 150 mg/d (0.6%), and conjugated equine estrogen (7.0%). The percentage of estrogen subjects reporting urinary incontinence was significantly greater than that for placebo and both doses of raloxifene (P = 0.02).
• Conclusions: During 3 years of follow-up, conjugated equine estrogen was associated with an increased incidence of reports of urinary incontinence in women with a prior hysterectomy and this was significantly greater than both placebo and raloxifene.
  
  
• Editorial Comment
  The authors analyze the effect of raloxifene, estrogen and placebo on the incidence of urinary incontinence in postmenopausal women that were participating in an osteoporosis prevention trial. Urinary incontinence was self reported and self rated by the patients during the study as mild, moderate or severe. There was no clear differentiation between symptoms of urinary urge incontinence, stress urinary incontinence, or mixed urinary incontinence. After three years of follow-up, the authors noted that estrogen was found to be associated with a statistically greater increase of urinary incontinence in women with prior hysterectomy than that found with either placebo or raloxifene.
  This paper raises interesting issues regarding the potential use of medical therapy as a prophylaxis against urinary incontinence. In addition, an interesting sidebar is made in the article about the potential effects of raloxifene on the incidence of female pelvic prolapse. The biological actions of raloxifene are mainly through the binding of estrogen receptors with secondary effect on estrogenic pathways. This result will potentially decrease the resorption of bone to that noted in the premenopausal state. The use of raloxifene has been noted to increase the risk of venous thromboembolism and thus the medication should be discontinued at least 3 days prior to any potential surgery, which would result in prolonged patient immobilization.
  Of specific note is that the incidence of incontinence in this patient population through self reporting was vastly lower than that previously reported in the United States (1). In addition, potential points of contention in this paper are self noted by the authors and do include that the screening for incontinence was not completed through a validated questionnaire and there was no differentiation between urge or stress incontinence. This article does bring up some fascinating points in the discussion section about the use of estrogen therapy and its effect on collagen content and architecture in the paraurethral tissues and vaginal epithelium.

Reference
1. Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, Hunt TL, Wein AJ: Prevalence and burden of overactive bladder in the United States. World J Urol. 2003; 20: 327-36.

Dr. Steven P. Petrou
Associate Professor of Urology
Mayo Clinic College of Medicine
Jacksonville, Florida, USA