Efficiency of hormone stimulation treatment before hypospadias surgery: Experimental study

Aim: Hypospadias is defined by the ventrally-placed urethral opening and is one of the most common congenital malformations, affecting 1 in 200-300 male newborns. In severe forms of hypospadias the penis may be small and the surrounding tissues may be weak. There is a relationship between size of the penis and surrounding tissues and the success of the hypospadias surgery. As the penis size gets smaller and the surrounding tissues are inadequate; the chance of surgical success decreases. Hormone treatments are used to increase penile size and tissue development. However, there is no consensus on the choice of hormone preparation to be used, how long the treatment should be done, and the timing of the surgical treatment to be performed. The purpose of this study, is to observe structural and histopathologic changes of hormone stimulation therapy methods in the healthy (without hypospadias) animal model and as a result of these observations, decide on the ideal surgical time period after hormone stimulation. Material and method: 50 Wistar Albino rats, which were 4-6 weeks old, were used. Rats were divided into 5 groups as parenteral human chorionic gonadotropin group, parenteral testosterone group, topical dihydrotestosterone group, parenteral control group and topical treatment control group. Penis diameter and length were measured weekly at the beginning of the application, throughout the study and after the application. Biopsies were taken from preputium for histopathologic examination at 0, 1, 3, 6, 7 and 8th weeks. Biopsies were evaluated for vascularity, epithelial thickness, inflammation and fibrosis. Results: In the group of which parenteral human chorionic gonadotropin was given; an increase of 56% in penile length, 58% in penile diameter and 84% in number of vessels in preputium biopsies was achieved. Increases in penile length, diameter and number of vessels were statistically significant when compared to the control group. The epithelial thickness score in the preputium biopsies was 2,2 and 3,4 in the first and last biopsies, respectively, and this increase was statistically significant. İnflamation score between third and seventh weeks, fibrosis score between third and sixth compare control groups was found to be low at a meaningfull level statistically. In the parenteral testosterone-administered group, an increase of 62% in the length of the penis, 59,8% in the diameter of the penis and 109% in the number of vessels in the preputium biopsies was observed. Increases in penile length, diameter and number of vessels were statistically significant when compared to the control group. Epithelial thickness score in the preputium biopsies was 2,2 and 3,5 in the first and last biopsies, respectively, and this increase was statistically significant. Parenteral testosterone did not have a significant effect on inflammation. Fibrosis score was found to be statistically significantly lower between 3 and 7 weeks of study when compared to the control group. In the topical testosterone-administered group, an increase of 46% in the length of the penis, 59% in the diameter of the penis and 100% in the number of vessels in the preputium biopsies was observed. Increases in penile length and number of vessels were statistically significant when compared to the control group. The increase in penile size was significantly higher at 3rd week of study when compared to the control group. Epithelial thickness score in the preputium biopsies was 2,3 and 3,3 in the first and last biopsies, respectively, and this increase was not statistically significant. Topical testosterone did not have a significant effect on inflammation. Fibrosis score was found to be statistically significantly higher in the third week of study compared to the control group. Conclusion: This study has shown that human chorionic gonadotropin, parenteral testosterone and topical dihydrotestosterone treatments are useful in increasing penile size and tissue quality before hypospadias surgery. It was observed that parenteral testosterone was the most effective among these hormone stimulation treatment regimens. In addition, this study showed that hormone stimulation treatments did not exacerbate inflammation and fibrosis, but periodically suppressed. The best time for surgical repair starting from the end of drug administration was found as after the 4th week in parenteral human chorionic gonadotropin group, after the 7th week in parenteral testosteron group and after the 1st week in testosteron group. Key Words: Hypospadias, preoperative hormone stimulation, rat preputium, experimental study, surgical timing