Estrogen Treatment for Urinary Incontinence

Abstract

DECIDING WHETHER TO TREAT POSTMENOPAUSAL women with urinary incontinence (UI) with estrogen has become increasingly difficult. The literature is divided but generally supportive. A Cochrane systematic review concluded that “estrogen treatment can improve or cure incontinence,” especially urge UI. Similarly, the International Consultation on Incontinence agreed in 2004 that “it seems reasonable to assume that estrogen therapy may be of benefit for the irritative symptoms of urinary urgency, frequency, and urge UI,” but noted that estrogen had little role in the treatment of stress UI. However, in the Cochrane combined meta-analyses of randomized controlled trials, the overall number of participants was small (for example, for the outcome of subjective cure and improvement of UI, the analysis included 179 women assigned to estrogen and 177 women assigned to placebo from a total of 9 trials). Although the large prospective Heart and Estrogen/Progestin Replacement Study (HERS) (n=1525) found that estrogen plus progestin increased UI rates, these findings could be applied only to women with ischemic heart disease. Both the Cochrane collaborators and the International Consultation on Incontinence admitted that specific recommendations could not be made regarding which estrogen formulation to use, optimal route of administration, duration of therapy, and which women with urge UI would be most likely to benefit. Media coverage about cardiovascular and other risks with estrogen from HERS and the Women’s Health Initiative (WHI) have cooled enthusiasm among clinicians and patients for estrogen use in general—and particularly for UI, for which other treatments are available. To address all of these uncertainties and questions, large, well-designed, randomized controlled trials that could be broadly generalized are needed. In this issue of JAMA, Hendrix et al present such a study examining UI outcomes among the thousands of women participating in the WHI. This study has the clear advantages of larger size, multicenter design, and longer follow-up (1-3 years) than most previous randomized controlled trials, and unlike HERS is generalizable to the great majority of postmenopausal women. Their finding of higher rates of UI in women treated with estrogen with or without progestin suggests that estrogen has no place in the UI treatment armamentarium. But is this really the end of the story regarding estrogen treatment for UI? The answers appears to be both yes and no. The authors evaluated the incidence of new and worsening UI in the 2 WHI studies: conjugated equine estrogen (CEE) treatment alone compared with placebo (estrogen alone trial), and combined hormonal treatment of CEE plus medroxyprogesterone acetate (MPA) compared with placebo (E P trial). In women who were continent at baseline, estrogen significantly increased the risk of stress UI (CEE MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.772.62]) and mixed UI (CEE MPA: RR, 1.49 [95% CI, 1.102.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]) at 1 year. An increased risk of urge UI was found in the estrogen alone trial (RR, 1.32; 95% CI, 1.10-1.58). Women who were incontinent at baseline developed larger and more frequent amounts of leakage with both CEE alone and CEE MPA. Subgroup analyses demonstrated that CEE alone and CEE MPA particularly increased the amount and frequency of UI in older women, and CEE MPA increased the risk in women who were 15 years or more from menopause. Limitation of activities by UI and the degree of bother of urine leakage also increased in the groups randomized to CEE alone and CEE MPA. Moreover, the authors show that the risk of UI with CEE MPA did not diminish over 3 years, although the risk with CEE alone was no longer significant. Incident UI at 1 year persisted for the majority of women (about 70%), regardless of treatment group assignment. The authors strongly conclude that “conjugated equine estrogens with or without progestin should not be prescribed for the prevention or relief of UI.” One notable aspect of their findings is the high baseline rate of UI in WHI participants (64%), which is at or above the upper limit of median rates found in systematic reviews of UI epidemiology (30%-40% for middle-aged women