Some 23,296 postmenopausal women aged 50 to 79 years participating in the Women's Health Initiative study were randomly assigned, based on hysterectomy status, to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/day of conjugated equine estrogens plus 2.5 mg/day of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/day of CEE. After one year of treatment, compared with placebo, CEE alone and CEE + MPA increased the incidence of urinary incontinence among continent women and worsened the incontinence among women who were symptomatic at baseline. The increased incidence of incontinence was seen for all types of incontinence (stress, urge, and mixed), although the increased incidence for urge incontinence was significant only in the CEE trial.

Comment: Although hormone therapy is often prescribed to treat urinary incontinence, the results of the present study demonstrate that CEE (Premarin®) actually makes the problem worse. This study adds to the list of documented adverse effects of CEE, which now include increased risks of breast cancer, cognitive decline, dementia, thrombophlebitis, gallbladder disease, and possibly heart disease. This growing list of adverse effects is an ongoing embarrassment for the medical community which, until a few years ago, was vigorously recommending that most postmenopausal women receive CEE.

For more than 20 years, Dr. Jonathan Wright and others have pointed out that CEE, which is derived from horse urine, contains a wide range of hormonally active compounds that are foreign to the human body, and may therefore not be an appropriate treatment for humans. Moreover, the fact that CEE is derived from pregnant mares' urine indicates that even the horses did not want it.

Hopefully, the impending demise of CEE will remind practitioners that hormone-replacement therapy should more logically consist of low doses of those hormones that are manufactured by the human ovary (estrogens, progesterone, DHEA, and testosterone), individualized according to each person's needs.

Hendrix SL, et al. Effects of estrogen with and without progestin on urinary incontinence. JAMA 2005;293:935-948.