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This version published online on August 7, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1110
A more recent version of this article appeared on November 1, 2007
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Right arrow Male Endocrinology

Submitted on May 18, 2007
Accepted on August 1, 2007

Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis

Carol A. Davis-Dao, Ellenie D. Tuazon, Rebecca Z. Sokol, and Victoria K. Cortessis*

Department of Preventive Medicine, Department of Urology, Department of Obstetrics, Gynecology and Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033

* To whom correspondence should be addressed. E-mail: cortessi{at}usc.edu.

Context: Many studies have investigated the association between male infertility and trinucleotide repeat polymorphisms in the androgen receptor (AR) gene, but no comprehensive meta-analysis of all published studies has been conducted.

Objective: Our goals were to summarize published data on associations between AR CAG and GGC repeat lengths and male infertility, and to investigate sources of variation between study results.

Data Sources: We searched for reports published before October 2006 using Medline, PubMed and Web of Science.

Study Selection: All selected studies included the following: a case group with infertility as measured by semen parameters, a control group of known or presumed fertile men, and measurement of CAG and/or GGC repeat lengths among cases and controls. Thirty-nine reports were selected based on these criteria, and 33 were ultimately included in the meta-analysis.

Data Extraction: One investigator extracted data on sample size, mean and standard deviation of trinucleotide repeat length, and study characteristics.

Data Synthesis: Estimates of the standardized mean difference (SMD) (95% confidence interval) were 0.19 (0.09–0.29) for the 33 studies, and 0.31 (0.14–0.47) for a sub-set of 13 studies that used more stringent case and control selection criteria. Thus, in both groups, cases had statistically significantly longer CAG repeat length than controls. Publication date appeared to be a significant source of variation between studies.

Conclusions: This meta-analysis provides support for an association between increased androgen receptor CAG length and idiopathic male infertility, suggesting that even subtle disruptions in the androgen axis may compromise male fertility.


Key words: Androgen receptor • male infertility • trinucleotide repeat polymorphism • CAG • GGC




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