Further grounds for abandoning the concept of testicular dysgenesis syndrome: a response to the paper of Akre and Richiardi (2009)

The concept of testicular dysgenesis syndrome (TDS) was originally propounded by authors who noted that the components of the syndrome [hypospadias, impaired sperm quality, cryptorchidism and testicular cancer (TC)] all seem to be risk factors for one another. So they hypothesized that there is a common cause viz high intrauterine estrogen levels (Sharpe and Skakkebæk, 1993; Skakkebæk et al., 2001). However, evidence seems sparse that intrauterine estrogen levels are implicated in one of the components of the syndrome—TC (Cook et al., 2009; Wohlfahrt et al., 2009). Moreover, doubt has been expressed by critics that the components actually do share causes (Storgaard et al., 2006; Akre and Richiardi, 2009). Indeed this doubt prompted the latter authors to suggest that the concept of TDS should be abandoned. Here I offer support for this suggestion. Without denying that some cases of TC may have prenatal causes, I adduce three forms of evidence to suggest that another factor—low post-natal testosterone (T)/gonadotrophin (G) ratios (T/G ratio)—also predisposes to (at least some cases of) this cancer. Moreover, since T levels are also markers of sperm quality (another component of TDS; Zalata et al., 1995), the whole notion of the syndrome seems in disarray. This is so because I take a syndrome (of this sort) to require by definition a. a cause (or causes) common to all its components, and b. no other major cause.