Effects of Sex Hormones on Calcium Oxalate Nephrolithiasis in Ethylene Glycol-Treated Rats / 대한비뇨기과학회지

ABSTRACT

PURPOSE: Sexual differences in the incidence and crystalline composition of urinary stones in humans are well-known, but it is unclear why men have a higher incidence of calcium oxalate stones than women. We investigated the effects of sex hormones on stone formation using an ethylene glycol (EG)-induced urolithiasis model in rats. MATERIALS AND METHODS: Adult Sprague-Dawley rats were divided into 13 groups of 10 each, segregated by sex. Two groups of rats were untreated to serve as male and female controls. The other 11 groups were fed a 1% EG lithogenic diet for 4 weeks. Among these, 2 groups were males and females otherwise not treated; two groups were neutered with bilateral orchiectomies or oophorectomies as appropriate; two groups were neutered and received subcutaneous testosterone; 2 groups were neutered and received subcutaneous estradiol; 2 groups were intact males and females administered the opposite sex hormone; and 1 group was intact males given finasteride orally. Serum testosterone, estrogen, creatinine, electrolytes, 24-hour urine levels of oxalate and citrate, and creatinine clearance were measured. The crystal deposits were examined by light and polarizing microscopes. RESULTS: Exogenous testosterone promoted, whereas estrogen inhibited, calcium oxalate stone formation in EG-treated rats. Finasteride administration significantly decreased urinary oxalate excretion and calcium oxalate deposition, compared with controls. Urinary citrate was significantly decreased in EG-treated female rats, but was not influenced by neutering and/or exogenous sex hormones in either sex. There were no significant differences in serum concentrations of creatinine, sodium, or potassium among the control and experimental groups. CONCLUSIONS: Our data suggest that testosterone promotes and estrogen inhibits calcium oxalate stone formation, and that dihydrotestosterone may be partially responsible for the exaggerated hyperoxaluria in EG-treated rats. Additionally, sex hormones have a lesser influence on urinary citrate than oxalate.