Molecular diagnosis of 5α-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism.

CONTEXT Although a rare occurrence, previously undiagnosed disorders of sex development (DSD) with hyperandrogenism are sometimes detected by hormonal screening during the international sports competitions. Identifying the cause of XY,DSD raises medical and ethical concerns, especially with regard to issues of the eligibility to compete. OBJECTIVE The aim of this study was to determine whether the detection of high plasma T in young elite female athletes during hormonal screening would reveal an unsuspected XY DSD. SETTING The study was performed in the Nice and Montpellier University Hospitals (France), which collaborate as reference centers for DSD in elite athletes on behalf of sports governing bodies. PATIENTS Four cases of elite young athletes with female phenotypes but high plasma T detected during hormonal screening were investigated for undiagnosed XY DSD. MAIN OUTCOME MEASURES Evaluation of clinical, biological, radiological (magnetic resonance imaging and dual-energy x-ray absorptiometry) and genetic characteristics was conducted. RESULTS The 4 athletes presented as tall, slim, muscular women with a male bone morphotype, no breast development, clitoromegaly, partial or complete labial fusion, and inguinal/intralabial testes. All reported primary amenorrhea. The hormonal analysis evidenced plasma T within the male range, the karyotype was 46, XY, and molecular analysis of the 5α-reductase type 2 (srd5A2) gene identified a homozygotic mutation in 2 cases, a heterozygotic compound in 1 case, and a deletion in 1 case. CONCLUSION 5α-Reductase deficiency should be investigated in elite young female athletes with primary amenorrhea and high male T levels detected during antidoping programs to identify undiagnosed XY DSD.