Update on cryptorchidism: endocrine, environmental and therapeutic aspects

Summary

Cryptorchidism is the most frequent developmental abnormality in boys, present in more than 1% of infants above three months of age. It is associated with an increased risk of infertility and testicular cancer. The etiological quest is often disappointing, except in bilateral cases or associated malformations. Recent focus is on genetic and environmental aspects. Animal models have revealed the role of genes encoding for proteins implicated in testicular migration (InsI3, Hoxa 10), but in humans results are less convincing. While some degree of endogenous hormonal abnormality is suspeeted in some patients, the endocrine disruptor hypothesis is also tested. It is unclear whether the incidence of cryptorchidism has really increased, or whether there is only a better screening for this condition. However, other male reproductive problems, such as subfertility, hypospadias and testicular cancer seem on the rise. This secular trend suggests the possible in utero impact of hormonally active environmental factors, such as pesticides with estrogenic or antiandrogenic effect, and is consistent with the increased risk of cryptorchidism observed in the sons of mothers exposed to diethylstilbestrol during pregnancy. From a therapeutic point of view, there is an agreement that the correction of cryptorchidism is needed, but there is controversy on the best medical and/or surgical approach and on the optimal timing. There is a recent trend in proposing early therapeutic intervention, before 1 yr of age, in the hope of improving fertility; however, there is no proof that such a strategy can reduce the risk of testicular cancer.

2003 Study Abstract

” …Prenatal exposure to diethylstilbestrol (DES) is a well known factor causing cryptorchidism in different animal models and in man. In addition, 100 g/kg/day of DES given to pregnant mice from day 9 to 17 prevent normal gubernaculum development and is associated with a three-fold decrease in Insl3 mRNA expression, with no change in steroidogenic factor 1 (SF1) expression. These results are similar to those obtained with β-estradiol, α-estradiol and DES also in mice. …

… In an American case-control study, the relative risk of cryptorchidism was 2.8 in boys whose mothers were treated with estrogens (DES, estradiol, or a contraceptive pill) during pregnancy. Regarding the risk linked to DES, results vary from one study to another; Gill reports a frequency of 8% compared to 1% in controls. …”

Sources

  • Update on cryptorchidism: endocrine, environmental and therapeutic aspects, Journal of endocrinological investigation, NCBI PubMed, PMID: 12952375, 2003 Jun.
DES DIETHYLSTILBESTROL RESOURCES

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