An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men.

Objective To describe the influence of the TTTA aromatase polymorphism (TTTAn) on the relation between obesity and plasma estradiol (E 2 ) in obese men. Design A 2-year cohort study. Setting Clinical research center. Patient(s) Severely obese men (31 who had had gastric bypass surgery and 118 controls). Intervention(s) Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma E 2 , and other hormonal levels were determined at baseline and 2-year follow-up. Main Outcomes Measure(s) Relationships between weight and changes in weight and plasma E 2 were examined in relation to the TTTAn polymorphism. Result(s) The mean age was 46.5 ± 10.82 years, and mean body mass index was 47.1 ± 8.46 kg/m 2 . The most common repeats were 7 and 11. TTTAn number did not correlate with plasma E 2 in the univariate analysis. When patients were stratified per weight group, the correlation between plasma E 2 and weight was seen only among men with a higher TTTA repeat at baseline and 2 years. Similarly, only men with higher TTTA exhibited reduced E 2 levels after weight loss. Conclusion(s) A higher TTTA repeat is associated with a strengthened relationship between obesity and E 2 . The well-established effect of increased weight on plasma E 2 appears to be absent in men with low TTTA numbers.