title: Testicular dysgenesis syndrome and the estrogen hypothesis: a quantitative meta-analysis.
abstract: BACKGROUND
  Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS). The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993. The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive.
  
  
  OBJECTIVE
  We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents. Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-alpha-mediated mode of action was specifically explored.
  
  
  RESULTS
  We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews. Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer.
  
  
  CONCLUSIONS
  The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action. Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.
authors.affiliation: Centre for Environmental Policy, Imperial College London, UK.
authors.forename: Olwenn V
authors.initials: OV
authors.lastname: Martin
authors.forename: Tassos
authors.initials: T
authors.lastname: Shialis
authors.forename: John N
authors.initials: JN
authors.lastname: Lester
authors.forename: Mark D
authors.initials: MD
authors.lastname: Scrimshaw
authors.forename: Alan R
authors.initials: AR
authors.lastname: Boobis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Voulvoulis
mesh_terms: D004967:Estrogens / Q000502:physiology*; D006801:Humans; D008297:Male; D013737:Testis / Q000002:abnormalities*
chemical_list: D004967:Estrogens