MEDICATIONS: HORMONE THERAPY INCREASES RISK OF URINARY INCONTINENCE

March 1, 2005 — What has been considered a treatment for urinary incontinence — estrogen alone or with progestin — has been found to increase the incidence of incontinence in postmenopausal women, according to a study in the February 23 issue of the Journal of the American Medical Association.

Menopausal hormone therapy (MHT) consisting of oral estrogen plus progestin or estrogen alone has long been used to treat postmenopausal women and, until recently, was credited with many benefits well beyond the indications for symptomatic relief of hot flashes, night sweats, and vaginal dryness, according to background information in the article. One of the purported benefits of MHT was to improve the symptoms of urinary incontinence (UI), and it has often been prescribed to treat UI.

Susan L. Hendrix, D.O., of the Wayne State University School of Medicine and Hutzel Women's Hospital, Detroit, and colleagues conducted a study to determine the effects of MHT (estrogen and progestin or estrogen alone) on the 1-year incidence and severity of symptoms of stress (incontinence that occurs when involuntary pressure is put on the bladder by coughing or laughing or sneezing or lifting or straining), urge (incontinence that is generally attributable to involuntary contracts of the bladder muscle), and mixed UI (involuntary leakage associated with urgency and also with exertion, effort, sneezing, or coughing) in healthy postmenopausal women. The researchers analyzed data from the Women's Health Initiative (WHI): multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998. Existence of any UI symptoms was known for 23,296 participants at baseline and one year. Women were randomized to receive estrogen alone (conjugated equine estrogen, [CEE]), estrogen plus progestin (CEE plus medroxyprogesterone acetate [MPA]), or placebo.

The WHI trials were designed to evaluate the effects of MHT using estrogen and progestin or estrogen alone in preventing coronary heart disease and hip fractures in postmenopausal women. Both trials ended prematurely because more harm than benefit was observed.

The researchers found that menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (1.87-fold increased risk with CEE + MPA; CEE alone, 2.15-fold increased risk), followed by mixed UI (1.49-fold increased risk with CEE + MPA; CEE alone, 1.79-fold increased risk). The combination of CEE + MPA had no significant effect on developing urge UI, but CEE alone increased the risk by 1.32 fold. Among women who reported having UI at baseline, both frequency and amount of UI worsened in both trials. Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities and bothered or disturbed them at one year.

"In conclusion, these results from a large, double-blind, placebo-controlled, randomized clinical trial, conducted in multiple centers with an ethnically diverse group of healthy postmenopausal women, indicate that MHT use does not confer protection against any type of UI. On the contrary, both CEE alone and CEE + MPA increased risk of new onset UI among continent women and worsened the characteristics of UI among symptomatic women. Considerations regarding the use of hormone therapy by postmenopausal women for any duration should incorporate the current findings into the established risks and benefits of these agents," the authors conclude.

Editor's Note: The National Heart, Lung, and Blood Institute funds the Women's Health Initiative program. Wyeth-Ayerst provided the study pills (active and placebo). Dr. Hendrix has received research funding from Lilly. None of the other authors reported any disclosures.

Editorial: Estrogen Treatment for Urinary Incontinence — Never, Now, or in the Future?

In an accompanying editorial, Catherine E. DuBeau, M.D., of the University of Chicago, examines the conclusions that can be derived from the findings by Hendrix et al.

"First, clinicians should no longer prescribe long-term oral conjugated equine estrogens for treatment of urge, stress, or mixed UI in postmenopausal women aged 50 years or older. Hendrix et al have performed an important service by placing UI among the ranks of other significant women's health problems that warrant formidable organizational, funding, and analysis efforts. Such trials carry enormous impact among both physicians and the public, which can lead to fruitful, if complicated, dialogues about the specific health problems investigated. It would be extremely positive if these trial results prompted women with UI — half of whom never discuss their condition with a physician — to ask their physicians about the many other available treatments for UI."

"Second, this trial is not the final word on using estrogens to treat UI. Whether topical estrogens might prove beneficial remains unknown, especially on a short-term basis and/or in combination with other therapies," Dr. DuBeau writes.