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Serum Concentrations of Estradiol and Free T₄ Are Inversely Correlated With Sperm DNA Damage in Men From an Infertility Clinic

NARENDRA P. SINGH

RUSS HAUSER^,

From the ^* Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan; the Department of Bioengineering, University of Washington, Seattle, Washington; the Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts; and the Vincent Memorial Obstetrics and Gynecology Service, Andrology Laboratory and In Vitro Fertilization Unit, Massachusetts General Hospital, Boston, Massachusetts.

Correspondence to: Dr John Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S Observatory St, Ann Arbor, MI 48109 (e-mail: meekerj{at}umich.edu).

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 T₄ 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 T₄ 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 T₄ quartile had 92% decreased odds of being categorized in the highest Tail% quartile compared with men in the lowest free T₄ quartile. These results suggest that estradiol and free T₄ may have a protective effect against sperm DNA damage, but future mechanistic and epidemiologic studies are needed to confirm these findings.

     Key words: Chromatin, comet assay, epidemiology, hormone, human