Chapter 1 continued
7.1. Frequency of Hypospadias
In the specialist field of pediatric urology, it is reported that hypospadias is a common congenital malformation. The estimations of frequency are placed between 1 in 300 (0.3 %) and 1 in 250 (0.4%) of male births (Baskin, 2000 ; Sheldon & Duckett, 1987 ; Paparel et al., 2001).
7.2. Incidence of hypospadias
However, certain scientific studies published towards the end of the 1990s reported an increasing incidence of hypospadias in several western countries. Based upon the analysis of American and European surveys of congenital malformations and earlier epidemiological reports, Paulozzi, Erickson et Jackson (1997) observed that the rate of hypospadias almost doubled  between 1970 and 1990 in the United States. Paulozzi (1999) also stated that similar increases in hypospadias had been reported in several European countries .
A series of recent publications, based upon hospital birth registers, have reported an increase in hypospadias. One study carried out by Pierik, Burdof, Nijman et al. (2002) produced evidence that the frequency of hypospadias rose to 0.7 percent in child health centers situated in the south west region of the Netherlands; this represented a rate 6 times higher than that generally reported in the region by national registers.
Another study by Hussain, Chagtai, Herndon et al. (2001) showed an incidence 10 times higher (4.0% vs 0.4 %) of hypospadias in 2000 compared to 13 years previously (1987) in neo-natal intensive care units in the USA (Connecticut) ..
Other studies using different registers have discovered a higher frequency of hypospadias than is generally recognized. After an analysis of American national military registers, Gallentine, Morey and Tompson (2001) estimated a frequency of hypospadias rising to 0.7% (709 cases of hypospadias counted in 99210 males). By contrast, this frequency (0.7%) is almost double that calculated by other researchers in Italy, in a male population over 18 years of age who were examined during enrolment for military service, which reached 0.36% (42 cases per 11649 males) (Mondaini, Ponchietti, Bonafè et al., 2001).
What explanations does the scientific community give regarding these rises?
The concept of endocrinal disruption, as discussed above, has been increasingly accepted and proposed as a way of accounting for the increased incidence of hypospadias observed in more industrialized nations (Dolk, 1998 ; Harrison, Holmes & Humfrey, 1997 ; Wakefield, 2001).
However, a number of authors agree that new epidemiological research of a multi-disciplinary nature must be carried out, in order to clarify the part played by chemical substances disrupting endocrine function in the reported increased frequency of hypospadias (Baskin et al., 2001; Rittler & Castilla, 2002; Sultan et al., 2001; Toppari et al. 2002; Weber et al., 2002).
Taken together, the published studies draw attention to the fact that nowadays hypospadias is a congenital condition far more common than is normally supposed (Sharpe, 2003).
Hypospadias benefits from a vast literature concerning the investigation of its physical aspects. Currently, different medical disciplines are working together to understand better the etiology of this condition. The data currently available on this subject stem from endocrinology, molecular biology, epidemiology and even eco-toxology. Although some considerable progress has been made in these fields, supplementary research is required to better understand the factors combining to produce this condition.
This review of the relevant literature shows that hypospadias is a much more common condition than is generally supposed, that it is becoming increasingly common, and indeed that it is more common now than ever before.
Footnotes to Chapter 1
 The mechanisms of prenatal sexual differentiation have been to a large part elucidated by the many experiments carried out, some 50 years ago, on different animal species (batrachians, mammals and birds) (for a review see Aron, 1973, pp. 109-121).
 The gonadic outline is called undifferentiated when it contains both ovarian and testicular tissue.
 SRY : Sex determining Region Y gene. Only a tiny region (known as the ‘short arm’ of the Y chromosome contains the gene(s) of sexual determination (see Haqq & Donahoe, 1998, pp. 2-5).
 In the absence of SRY, the undifferentiated gonad develops as an ovary.
 In the absence of AMH (anti-Müllerian hormone) and testosterone, sexual differentiation follows a fixed pattern, characterized by the regression of the Wolfian ducts and the development of Müllerian ducts (the upper third of the vagina and uterus).
 This severity of hypospadias is also classified as vulviform; the external genital organs of the newborn male (46XY) can appear as the phenotypic feminine.
 The prepuce is known as a dorsal hooded foreskin.
 In fact, certain varieties of hypospadias with a complete prepuce have been reported in the literature (see, for example, Cold & Taylor, 1999).
 A penis of under-developed size, sometimes observable in hypospadias, is not to be confused with what has been called a micropenis or microphallus: here the penis is morphologically normal and the urethra’s outlet is well positioned at the end of the glans, but the size is very much reduced in comparison to the available norms (Bourgeois, 2003).
 The non-descent of testicles (without the association of hypospadias) is a condition frequently encountered in newborns of the masculine sex, its incidence being estimated at around 3 percent of full-term newborns (Leissner, Filipas, Wolf & Fish, 1999).
 Impacting of the penis in the scrotum is defined by the presence of scrotal skin, either low or high on the body of the penis. Total impacting is rare, but if this is the case only the dorsal face is visible, the ventral side remains stuck in the scrotum.
 The notion of sexual ambiguity relates to an undifferentiated or badly differentiated appearance of the external genital organs, or to a state of discordance between the internal and external genital organs (Encha-Razavi & Escudier, 2000). The notion of intersexuality refers to a variation of normal development whereby the appearance of the external genitals makes it difficult to assign a sex to the child at birth (Hugues, 2002).
 The balano-preputial ridge is the anatomical transition between the glans and the shaft of the penis.
 The explanation of such a classification is relatively easy to explain: the position of the urethral meatus is considered an untrustworthy criterion for judging the severity of hypospadias as, in general, the meatus moves backwards after surgical repair of the chordee (orthoplasty), worsening to some extent the degree of hypospadias confirmed initially (De Sy & Hoebeke, 1996).
 The concept of endocrinal disturbance refers to the molecules capable of imitating sexual hormones naturally produced by the body (xenoestrogens) or of blocking certain hormones (anti-androgens) at the stage crucial for sexual development in utero (Toppari, 2002).
 I cite as an example the research of Facemire, Gross and Guillette (1995) and that of Guillette (2000) (in Florida, USA). In a first study, the researchers clearly gave evidence that the abnormally high presence of cryptorchidism, observed in a population of panthers, could be explained by the fact that these felines lived very close to an agricultural area where pesticides were widely distributed. (Facemire et al., 1995). In a second series of studies, the researchers noticed a notable diminishing of the penis size of alligators born in a polluted lake (Lake Apopka) following a leakage of toxic substances (Guillette, 2000; see also Semenza, Tolbert, Rubin et al., 1997).
 Diethylstilbestrol (DES) is a synthetic estrogen which was widely prescribed to pregnant women between 1938 and 1975 to prevent miscarriage. The effects of DES as evidenced are avowed to be transgenerational. In the article by Klip et al. (2002), the hypothesis is that DES would be associated with a disturbed function of the placenta, resulting in a diminishing of placental and fetal hormones which could disrupt fetal development; this would predispose a likelihood of hypospadias.
 The rate has gone from 20/10000 in 1970 to 40/10000 in 1993 in USA (Paulozzi et al., 1997).
 Norway, Sweden, United Kingdom, Denmark, Italy and France (for details see Paulozzi, 1999).
 Other American researchers have reported an incidence, also in neonatal intensive care units (in the Atlanta region), ten times higher than normally estimated in that particular population (11% vs 1%) (Gatti, Kirsch, Troyer et al., 2002).
Continued here: Chapter 2. (The rest of this material will be added as soon as possible…. please call back or email to check)