Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: Evidence in ovariectomized rodents

Purpose: Although detrusor hyperactivity with impaired contractility is a c ommon urodynamic finding in elderly subjects, to our knowledge its pathogen esis remains unknown. Biopsy studies indicate that subjects with detrusor h yperactivity and impaired contractility have ultrastructural evidence of dy sjunction and degeneration patterns in isolated detrusor hyperactivity and impaired contractility, respectively. Based on the known cellular effects o f estrogen we postulated that declines in ovarian hormone production may co ntribute to the pathogenesis of detrusor hyperactivity with impaired contra ctility. Materials and Methods: Mature 13 to 14-month-old female Fisher 344 rats wer e studied 4 months after bilateral ovariectomy or sham surgery. Detrusor st ructure was evaluated by electron microscopy and contractility was evaluate d by muscle strip studies. Results: After bilateral ovariectomy detrusor smooth muscle decreased by 25 % with a 12% decrease in the number of nucleated muscle profiles and degene rative changes in many axons. Muscle strips from bilaterally ovariectomized animals generated 40% to 50% less tension per strip in response to carbach ol than strips of equal size from sham operated animals with no apparent ch ange in muscarinic receptor affinity. Conclusions: Bilateral ovariectomy resulted in many changes of the degenera tion ultrastructural pattern but in none of the characteristic features of the dysjunction pattern. Our results indicate that the mature rodent detrus or and its innervation are sensitive to prolonged ovarian hormonal deficien cy, contributing to impaired contractility in rodents. Future studies are r equired to establish whether estrogen has a role in the degeneration ultras tructural pattern or impaired contractility in humans.