HRT linked to increase in urinary incontinence risk: but other research suggests estrogen may protect against irritative symptoms

OB/GYN News, Nov 15, 2001 by Kathryn DeMott

NEW ORLEANS -- Increasing evidence suggests that hormone replacement therapy, once thought to be protective against urinary incontinence, may actually increase a woman's risk for the disorder, experts said at the annual meeting of the North American Menopause Society.

In a poster presentation, Dr. Steven Goldstein of New York University New York, and his associates found that among 158 women randomly assigned to take 0.625 mg conjugated equine estrogen daily for 3 years, 7% had new or worsened episodes of urinary incontinence, compared with 1.3% among those women who took a placebo, a difference that was statistically significant.

Raloxifene, however, was not associated with elevated risks of urinary incontinence. Among the 309 women who took low-dose (60 mg/day) and high-dose (150 mg/day) raloxifene, the rates of urinary incontinence were 0.7% and 0.6%, respectively.

In addition, all the women in the raloxifene groups who reported preexisting incontinence at baseline experienced improvement, according to findings from the study, which was funded by Lilly Research Laboratories, the Indianapolis-based manufacturer of raloxifene (Evista). The prevalence of incontinence at baseline was similar across all groups.

Still, these findings need to be weighed against those of dozens of studies showing that estrogen is actually protective against irritative symptoms of urinary incontinence, Dr. Douglass Hale, codirector of the female pelvic medicine and reconstructive surgery fellowship at Indiana University! Methodist Hospital, Indianapolis, said in an interview Dr. Hale is a former paid consultant to Wyeth-Ayerst Pharmaceuticals, which markets estrogen, but is no longer affiliated with the company.

While estrogen has never been shown to prevent stress incontinence, some have theorized that estrogen may ease irritative symptoms, such as urge and frequency, by acting on estrogen receptors vaginally urethrally and in the trigone.

The disappointing findings on hormone replacement therapy (HRT) echo those from the Heart and Estrogen! Progestin Replacement Study or HERS trial. In a sub-analysis involving 1,525 women with incontinence at baseline, 39% of the women assigned to take conjugated estrogens plus medroxyprogesterone acetate experienced a worsening of their condition, compared with 27% of patients on placebo.

Conversely, incontinence improved among 26% of the women assigned to placebo and 21% taking HRT (Obstet. Gynecol. 97[1]:116-20, 2001).

Further evidence of the association between HRT and urinary incontinence has recently emerged from the Women's Health Initiative. In an analysis of more than 152,000 postmenopausal women, Dr. Susan L. Hendrix, an East Lansing, Mich.-based Women's Health Initiative investigator, and her colleagues found that current HRT users had significantly higher rates of stress incontinence (odds ratio of 1.71) and mixed incontinence (odds ratio of 1.57), compared with women who had never used HRT.

While these data do not establish a cause-and-effect relationship, they do suggest an association "that's extremely strong. So I don't think we can ignore it, and I don't think we can just pass it off. I think we have to look at [HRT use] as a possible risk factor" for urinary incontinence, she said.

The prevalence of urinary incontinence in Dr. Hendrix's study is also much higher than has been previously reported. Strikingly 66% of all the participants reported. having experienced urinary incontinence. Of those who reported any problem, 42% said they leaked more than once a week.

Dr. Hale suggested that the prevalence of incontinence reported in that study was approximately what one would expect to see in a nursing home and was out of line with prevalence data from every other study of women in the general population.

Of those women with incontinence, 39% reported having symptoms of stress incontinence, 38% had urge incontinence, and 58% had mixed incontinence.

Other factors that appeared to be associated with incontinence included being overweight, having a hysterectomy and early childbirth. History of hysterectomy increased the rates of all types of incontinence.

Women who gave birth at age 20 or younger also had an elevated risk of incontinence, with an odds ratio of 1.5, compared with women who delayed childbirth or who did not have any children.

A key weakness of all the studies is that none used valid instruments or urodynamic testing to qualify and quantify the severity of incontinence and the amount of urine leakage, Dr. Hale noted.