Abstract
Objectives: The effect of intramuscular human chorionic gonadotropin (HCG) administration on penile enlargement before genital surgery, its influence on penile skin histology and testicular descent were investigated. Methods: We examined 45 male patients (median age, 8 months; range 3 - 28) with total epispadias and classic bladder exstrophy, combined with cryptorchidism. 30 patients were administered 250 - 500 IU HCG intramuscularly 2 times per week for 3 weeks before reconstructive surgery. Skin biopsies were obtained for human epidermal growth factor (EGF) and human epidermal growth factor receptor (Her2/neu) determination. Skin specimens of the prepuce of 18 circumcised patients were used as controls. Post treatment testicle position was evaluated. Results: HCG caused a mean increase in penile length of 1.8 cm (p < 0.01) and in circumference of 1.2 cm (p < 0.05) as well as improved local vascularity in all patients. Compared to the controls, the penile skin of exstrophy/epispadias patients showed a significant decrease in the average amount per field of EGF and Her2/neu positive material (controls 81 % [mean 79, SE 2.3] vs. 31 % [mean 28, SE 3.6; p < 0.001]). Treatment with HCG led to an increase in average EGF and Her2/neu positive material by 10 % (mean 8, SE 2; p < 0.05). The potential side effects of HCG treatment were monitored 3 to 6 months postoperatively. Basal testosterone and LH levels were obtained in patients before and during therapy and postoperatively. Testicular descent was achieved in 21 patients (70 %). No significant side effects or complications were encountered in any of our patients. Conclusion: Mean EGF and Her2/neu values are decreased in the penile skin of exstrophy/epispadias patients. The use of preoperative HCG administration leads to an increase in EGF and Her2/neu values and significantly contributes to successful reconstruction in these patients, especially in cases with a paucity of penile skin and in patients who have undergone previous repairs. Temporary penile stimulation by HCG in patients with bladder exstrophy combined with cryptorchidism allows the penile operation to be carried out earlier and contributes to testicular descent while demonstrating negligible side effects.
Key words
HCG - penile reconstruction - bladder exstrophy - total epispadias - epidermal growth factor
References
-
1 Ashcraft K W. Pediatric Urology. Philadelphia; W. B. Saunders Company 1990
-
2
Baskin L, Sutherland R S, DiSandro M J, Hayward S W, Lipschultz J, Cunha G R.
The effect of testosterone on androgen receptors and human penile growth.
J Urol.
1997;
158
1113-1118
-
3
Baskin L.
Hypospadias. Anatomy, embryology, and reconstructive techniques.
Brazilian J Urol.
2000;
26
621-629
-
4
El-Galley R ES, Smith E, Cohen C, Petros J A, Woodard J, Galloway N TM.
Epidermal growth factor (EGF) and EGF receptor in hypospadias.
Br J Urol.
1997;
79
116-119
-
5
Fletterick R J.
Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.
BJU International.
2005;
96
2-10
-
6
Gearhart J, Jeffs R D.
The use of parenteral testosterone therapy in genital reconstructive surgery.
J Urol.
1987;
138
1077-1078
-
7 Greulich W W, Pyle S I. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford; Stanford University Press 1959
-
8
Gupta C, Jaumotte J.
Epidermal growth factor binding in the developing male reproductive duct and its regulation by testosterone.
Endocrinology.
1993;
133
1778-1782
-
9
Hadziselimovic F, Herzog B.
Cryptorchidism.
Ped Surg Int.
1978;
2
132-136
-
10
Husmann D A, Levy J B.
Current concepts in the pathophysiology of testicular undescent.
Urology.
1995;
46
267-276
-
11
Johnson J H.
The genital aspects of exstrophy.
J Urol.
1975;
113
701-708
-
12
Liu A, Davis R J, Flores C, Manon M, Seethaladshmi L.
Epidermal growth factor: receptor binding and effects on the sex accessory organs of sexually mature male mice.
J Urol.
1992;
148
427-431
-
13
Matlai P, Beral V.
Trends in congenital malformations of external genitalia.
Lancet.
1995;
108-112
-
14
Miyamoto H, Rahman M M, Chang C.
Molecular basis for the antiandrogen withdrawal syndrome.
J Cell Biochem.
2004;
19
3-12
-
15
Morrish D W, Bharwaj D, Siu O.
Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta.
J Clin Endocrinol Metab.
1987;
65
1282-1290
-
16
Schillinger J F, Wiley M J.
Bladder exstrophy: penile lengthening procedure.
Urology.
1984;
24
434-437
-
17 Silver R I, Yang A, Ben-Chaim J, Jeffs R D, Gearhart J P. Penile length in adulthood after exstrophy reconstruction. Gearhart J, Mathews R The Exstrophy-Epispadias Complex. New York; Kluwer Academic/Plenum Publisher 1999
-
18
Sundaresan S, Penuel E, Sliwkowski M.
The biology of human epidermal growth factor receptor 2.
Current Oncology Reports.
1999;
1
16-22
-
19
Vignozzi L, Vanelli G B, Morelli A.
Identification, characterization and biological activity of oxytocin receptor in the developing human penis.
Mol Hum Reprod.
2005;
14
378-389
-
20
Woodhouse C RJ, Kellett M J.
Anatomy of the penis and its deformities in exstrophy and epispadias.
J Urol.
1984;
132
1122-1132
Dr. Docent and Head I. A. Makedonsky
Department of Pediatric Surgery/Urology
Children's Hospital #3
49006 Dnepropetrovsk
Ukraine
Email: igor_makedonsky@yahoo.com
