Wrong Route Of Administration Research Articles

Discussion: The effect of estrogens

I n women, the genital and urinary tracts derive from a common embryologic origin, the primitive urogenital sinus, and both are sensitive to the effects of female sex steroids. Estrogen and progesterone receptors are present in the vagina, urethra, bladder, and pelvic floor and symptomatic, cytologic, and urodynamic changes in the lower urinary tract (LUT) have been demonstrated during the menstrual cycle, in pregnancy, and following the menopause. Deteriorating ovarian function at the time of the menopause results in an increased incidence of urinary symptoms, including frequency, nocturia, urgency, incontinence, and dysuria, as well as the development of recurrent urinary tract infections. These symptoms may present as “the urge syndrome” and estrogens have been prescribed, usually empirically, in an attempt to improve this distressing symptom complex. Unfortunately, there have been few controlled studies of estrogen therapy reported in the literature, despite the known large placebo response in the treatment of urge incontinence. Samsioe et al.1 entered 34 women 75 years of age into a double-blind, placebo-controlled, cross-over study of oral estriol (3 mg/day) for 3 months. Despite the lack of objective assessment, they found that urge incontinence and mixed incontinence were improved by estriol, although in women with stress incontinence there was no difference between estriol and placebo. Unfortunately, we have not been able to replicate these results. In a double-blind, randomized, placebo-controlled, multicenter study involving 64 postmenopausal women with “the urge syndrome,” 3 mg/day oral estriol produced both subjective and objective improvement in urinary symptoms, particularly urgency and nocturia, but was not significantly better than placebo.2 IosiP has shown that urogenital atrophy, a late manifestation of estrogen deficiency, is completely relieved only after 1 year of treatment with 0.5 mg estriol suppositories and that symptoms recur with discontinuation of treatment. It is quite possible that 3 mg/day oral estriol is an inappropriate estrogen, given by the wrong route of administration, or given at too low a dose. It is unclear whether low-dose topical therapy, which improves genital atrophy without significant endometrial stimulation, is sufficient to treat urinary symptoms. Indeed, it is possible that estrogen is actually no better than placebo for the management of postmenopausal women with the urge syndrome, although Fantl et a1.4 have suggested that estrogen supplementation raises the sensory threshold of the bladder. We have subsequently assessed the efficacy of sustainedrelease 17P-estradiol vaginal tablets in the management of postmenopausal urinary urgency (Benness CJ, Wise BG, and Cardozo LD: unpublished data). These tablets are well absorbed from the vagina and have been shown to induce mat-