Serum concentrations of estradiol and free T4 are inversely correlated with sperm DNA damage in men from an infertility clinic.

Sperm DNA damage adversely affects male fertility and contributes to poorer embryo development and lower pregnancy rates. Endogenous hormones are critical to spermatogenesis and maintenance of male reproductive function and likely play an important role in human sperm DNA integrity, but this relationship is not fully understood. The present study measured serum hormone levels and sperm DNA damage with the neutral comet assay in 362 male partners of infertile couples. When sperm concentration and other potential confounding variables were included in multiple linear regression, serum estradiol and free T(4) levels were inversely associated with sperm DNA damage. Among other statistically significant associations that were observed, an interquartile range (IQR) increase in estradiol was associated with a 6.3% decline (95% confidence intervals: -9.7%, -2.9%) in comet extent and a 16.2% (-22.4%, -9.2%) decline in the percentage of DNA in the comet tail (Tail%), whereas an IQR increase in free T(4) was associated with a 24.4% (-31.5%, -17.4%) decline in Tail%. Likewise, in multiple logistic regression, men in the highest estradiol quartile had an 81% reduced risk of having a comet extent value in the highest quartile compared with men in the lowest estradiol quartile. Men in the highest free T(4) quartile had 92% decreased odds of being categorized in the highest Tail% quartile compared with men in the lowest free T(4) quartile. These results suggest that estradiol and free T(4) may have a protective effect against sperm DNA damage, but future mechanistic and epidemiologic studies are needed to confirm these findings.