How valid is the prenatal estrogen excess hypothesis of testicular germ cell cancer? A case control study on hormone-related factors

Eur Urol. 2001 Dec;40(6):677-83; discussion 684. doi: 10.1159/000049857.


Purpose/aims: The prenatal estrogen excess hypothesis postulates abnormally high estrogen levels during pregnancy which predispose the developing gonad to testicular germ cell cancer (GCT) in adulthood. As no direct measurements are possible to support this hypothesis, evidence must come from clinical and epidemiological observations. The present study looked to surrogate parameters that purportedly point to high estrogenic influence in utero.

Methods/patients: In a case-control study design, 418 cases with GCT were compared to 636 controls having fractures, injuries or nephrolithiasis. A second comparison was done with 120 men suffering from malignant melanoma. The following factors were investigated: maternal and paternal age at birth of proband, birth-order, distribution of brothers and sisters in sibs of patients, sibship size, status of being a twin, status of being a singleton child, handedness, and frequency of breast cancer in mothers and sisters.

Results: Status of being a twin was significantly associated with GCT risk (OR 2.41; 95% CI 1.04- 5.63) if compared to men with fractures or stones. Comparison with melanoma controls showed only a nonsignificant trend. Frequency of breast cancer was insignificantly higher in mothers of GCT patients. Maternal age above 30 years was associated with decreased risk of GCT, which is contradictory to the hypothesis. No other parameter was significantly different in cases and controls.

Conclusion: The present investigation failed to produce evidence for the estrogen excess hypothesis. Obviously, the parameters tested are only weak indicators of estrogenic influence during embryogenesis. Thus, the sample size and statistical power of the trial might have been too low to show any significant association. But, assessing the negative results of this study in light of equally negative results in previous investigations, the estrogen excess hypothesis still remains to be hypothetic.

MeSH terms

  • Adult
  • Birth Order
  • Breast Neoplasms / epidemiology
  • Case-Control Studies
  • Estrogens / adverse effects*
  • Female
  • Germinoma / etiology*
  • Humans
  • Male
  • Maternal Age
  • Middle Aged
  • Paternal Age
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Factors
  • Testicular Neoplasms / etiology*
  • Twins


  • Estrogens