Anogenital Distance or Digit Length Ratio as Measures of Fetal Androgen Exposure: Relationship to Male Reproductive Development and Its Disorders

Context: Male reproductive disorders evident at birth or in young adulthood are remarkably common. They are hypothesized to comprise a testicular dysgenesis syndrome (TDS), with a fetal origin involving mild androgen deficiency. Evidence Acquisition: Testing this hypothesis requires seeing back in time.Two ways have been proposed: measurement of anogenital distance (AGD), or measurement of the 2:4 digit length ratio. This review assesses the evidence that they reflect fetalandrogenexposureandmightbeused to provide insight into the origin of TDS disorders. Evidence Synthesis: Supporting evidence for AGD derives from rat experimental studies that identified a fetal masculinization programming window, within which androgen action determines adult reproductive organ size, TDS disorders, and AGD. In humans, AGD is positively correlated to testis size, sperm count/fertility, penis length, and T levels, consistent with rat experimental data. The 2:4 digit ratio also shows associations with these parameters, but inconsistently between studies; evidence that the 2:4 digit ratio accurately reflects fetal androgen exposure is also equivocal. Conclusions: AGD appears to provide a reliable guide to fetal androgen exposure, although available data are limited. The next steps are to: standardize AGD measurement; obtain age-specific population data; and use AGD to evaluate the importance of fetal androgens in determining reproductive disorders and variation in testis/penis size and sperm count in the normal population. These studies should identify what, if any, clinical applications ofAGDmeasurement are feasiblefor example, its ability to predict adult-onset reproductive functionanddisorders.