Effects of Long-Term Dietary Soy Treatment on Female Urethral Morphology and Function in Ovariectomized Nonhuman Primates

Purpose: Agonistic effects of estrogen on the female urethra include an increase in contractile function, blood flow and mucosal hyperplasia. Whether such effects can be achieved by soy based phytoestrogen diets is unclear. We studied the effects of chronic phytoestrogen treatment on the structural and functional properties of the urethra in ovariectomized monkeys. Materials and Methods: Following ovariectomy 18 monkeys were fed a diet containing soy (9) or casein (9) based protein for 32 months. At necropsy the urethra and bladder were removed and the urethra was separated into 3 segments of equal length, including a proximal, a middle and a distal segment. Each urethral segment and 1 bladder segment was tested in vitro for functional responses to electrical field stimulation and pharmacological stimulation, and the proximal to distal segments were tested for urothelial thickness and mucosal area. Results: Electrical field stimulation produced frequency dependent contractile responses in the bladder, proximal and middle segments but not in the distal segment. Carbachol, phenylephrine and endothelin-1 produced concentration dependent contractions in all urethral segments. The maximum response decreased from the proximal to the distal segment (p <= 0.05). The maximum response in the proximal and bladder segments to pharmacological stimulation and electrical field stimulation as well as mucosal area and urothelial thickness were significantly higher in the treatment than in the control group (p <= 0.05). Conclusions: Chronic phytoestrogen treatment results in increased responsiveness of the proximal urethra to pharmacological and electrical stimulation, which is associated with an increase in urothelial thickness and mucosal area. This study indicates that dietary soy may have estrogen agonist effects on the urethra and bladder in estrogen deficient females.