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Low Risk of Impaired Testicular Sertoli and Leydig Cell Functions in Boys with Isolated Hypospadias

Centro de Investigaciones Endocrinológicas (R.A.R., P.B., R.T., S.G., I.B., S.M.C.), Hospital de Niños R. Gutiérrez, C1425EFD Buenos Aires, Argentina; Centro de Investigaciones en Reproducción (R.A.R.), Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina; and Institute of Maternal and Child Research (E.C., G.I., C.O., F.G.C.), School of Medicine, University of Chile, 836-0160 Santiago, Chile

Address all correspondence and requests for reprints to: Rodolfo Rey, M.D., Ph.D., CEDIE, Hospital de Niños R. Gutiérrez, Gallo 1330, C1425EFD Buenos Aires, Argentina. E-mail: rodolforey{at}cedie.org.ar.

Context: Isolated hypospadias may result from impaired testicular function or androgen end-organ defects or, alternatively, from hormone-independent abnormalities of morphogenetic events responsible for urethral seam.

Objective: The objective was to evaluate the relative prevalence of hormone-dependent etiologies in boys with isolated hypospadias.

Design, Patients, and Main Outcome Measures: We studied endocrine testicular capacity in 61 patients with isolated hypospadias and 28 with hypospadias associated with micropenis, cryptorchidism, or ambiguous genitalia. Serum anti-Müllerian hormone and inhibin B were used as Sertoli cell markers. A human chorionic gonadotropin test was performed to evaluate Leydig cell function.

Results: Testicular dysfunction was observed in 57.1% and androgen end-organ defects in 7.2% of patients with hypospadias associated with cryptorchidism, micropenis, or ambiguous genitalia. In the remaining 35.7%, the disorder was idiopathic. The presence of ambiguous genitalia predicted the existence of testicular or end-organ dysfunction with 81.8% specificity. Isolated hypospadias was associated in 14.8% of patients with testicular dysfunction and in 6.5% of cases with end-organ defects; in 78.7% of cases, the condition was idiopathic. The occurrence of isolated hypospadias ruled out the existence of testicular or end-organ disorders with 80.0% sensitivity. Altogether our data indicate that the risk for the existence of an underlying testicular or end-organ dysfunction is low in patients with isolated hypospadias (odds ratio, 0.13; 95% confidence interval, 0.05–0.36; P < 0.001).

Conclusions: Boys with isolated hypospadias are more likely to have normal endocrine testicular and androgen end-organ functions, suggesting that transient disruption of morphogenetic events in early fetal life may be the predominant underlying cause.

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