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Based on DNA analysis of a historical case, the authors describe how a female athlete can be unknowingly confronted with the consequences of a disorder of sex development resulting in hyperandrogenism emerging early in her sports career. In such a situation, it is harmful and confusing to question sex and gender. Exposure to either a low or high level of endogenous testosterone from puberty is a decisive factor with respect to sexual dimorphism of physical performance. Yet, measurement of testosterone is not the means by which questions of an athlete's eligibility to compete with either women or men are resolved. The authors discuss that it might be justifiable to use the circulating testosterone level as an endocrinological parameter, to try to arrive at an objective criterion in evaluating what separates women and men in sports competitions, which could prevent the initiation of complicated, lengthy and damaging sex and gender verification procedures.

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The clinical use of diethylstilbestrol (DES) by pregnant women has resulted in an increased incidence of genital carcinoma in the daughters born from these pregnancies. Also, in the so-called DES-sons abnormalities were found, mainly, the presence of Mullerian duct remnants, which indicates that fetal exposure to DES may have an effect on male sex differentiation. Fetal regression of the Mullerian ducts is under testicular control through anti- Mullerian hormone (AMH). In male mice, treated in utero with DES, the Mullerian ducts do not regress completely, although DES-exposed testes do produce AMH. We hypothesized that incomplete regression in DES-exposed males is caused by a diminished sensitivity of the Mullerian ducts to AMH. Therefore, the effect of DES on temporal aspects of Mullerian duct regression and AMH type II receptor (AMHRII) messenger RNA (mRNA) expression in male mouse fetuses was studied. It was observed that Mullerian duct regression was incomplete at E19 (19 days post coitum), upon DES administration during pregnancy from E9 through E16. Furthermore, analysis of earlier time points of fetal development revealed that the DES treatment had clearly delayed the onset of Mullerian duct formation by approximately 2 days; in untreated fetuses, Mullerian duct formation was complete by E13, whereas fully formed Mullerian ducts were not observed in DES-treated male fetuses until E15. Using in situ hybridization, no change in the localization of AMH and AMHRH mRNA expression was observed in DES-exposed male fetuses. The mRNA expression was quantified using ribonuclease protection assay, showing an increased expression level of AMH and AMHRII mRNAs at E13 in DES-exposed male fetuses. Furthermore, the mRNA expression levels of Hoxa 11 and steroidogenic factor- 1 (SF-1) were determined as a marker for fetal development. Prenatal DES exposure had no effect on Hoxa 11 mRNA expression, indicating that DES did not exert an overall effect on the rate of fetal development. In DES-exposed male fetuses, SF-1 showed a similar increase in mRNA expression as AMH, in agreement with the observations that the AMH gene promoter requires an intact SF-1 DNA binding site for time- and cell-specific expression, although an effect of DES on SF-1 expression in other tissues, such as the adrenal and pituitary gland, cannot be excluded. However, the increased expression levels of AMH and AMHRII mRNAs do not directly explain the decreased sensitivity of the Mullerian ducts to AMH. Therefore, it is concluded that prenatal DES exposure of male mice delays the onset of Mullerian duct development, which may result in an asynchrony in the timing of Mullerian duct formation, with respect to the critical period of Mullerian duct regression, leading to persistence of Mullerian duct remnants in male mice.