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 Aquisition: Testing this hypothesis requires 'seeing back in time'. Two ways have been proposed, measurement of anogenital distance (AGD) or of the 2:4 digit length ratio. This review assesses the evidence that they reflect fetal androgen exposure and might be used to provide insight into origin of TDS disorders.
Evidence Synthesis: Supporting evidence for AGD derives from rat experimental studies that identified a fetal 'masculinization programming window' (MPW), 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 testosterone levels, consistent with rat experimental data. The 2:4 digit ratio also shows associations with these parameters, but inconsistently between studies; evidence that 2:4 digit ratio accurately reflects fetal androgen exposure is also equivocal.
Conclusions: AGD appears to provide a reliable guide to fetal androgen exposure, though available data is limited. The next steps are to: standardize AGD measurement; obtain age-specific population data; 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 of AGD measurement are feasible, for example its ability to predict adult-onset reproductive function and disorders.
Written by:
Dean A, Sharpe RM. Are you the author?
MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Cres, Edinburgh EH16 4TJ, Scotland, UK.
Reference: J Clin Endocrinol Metab. 2013 Apr 8. Epub ahead of print.
doi: 10.1210/jc.2012-4057
PubMed Abstract
PMID: 23569219
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