Hypospadias and endocrine disruption: is there a connection?

Abstract

Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.

Hypospadias: anatomy, etiology, and technique

“…Hypospadias is one of the most common congenital anomalies occurring in approximately 1 of 200 to 1 of 300 live births [1]. Hypospadias is defined by an abortive development of the urethral spongiosum and ventral prepuce along with an arrest in the normal embryological correction of penile curvature (Fig.…”

Risk factors for hypospadias

“…Exposure during early gestation has been hypothesized to affect the developing Sertoli cells and Leydig cells, thereby increasing the risk of hypospadias, cryptorchidism, testicular cancer, and reduced semen quality later in life; all of these are conditions that have been described as different expressions of the Testicular Dysgenesis Syndrome [2,4,31]. Although the evidence for adverse effects of endocrine disruptors on human reproduction is limited, data from animal studies as well as observations on wildlife following environmental pollution are convincing [3,29].…”

Placental insufficiency in early gestation is associated with hypospadias

“…Hypospadias is one of the most common congenital anomalies in boys, affecting approximately 1 in 250 to 300 live births [1][2][3]. According to recent investigations, the prevalence of this condition is increased 10-fold in very lowbirth-weight infants [4,5].…”