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

Abstract

Objective To describe the influence of TTTAn aromatase polymorphism on the relation between obesity and plasma estradiol in obese men. Design A 2 years cohort study. Setting Clinical research center. Patients Severely obese Caucasian men (31 had gastric bypass surgery and 118 controls). Intervention Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma estradiol and other hormonal levels were determined at baseline and two years follow up. Main outcomes measures Relationships between weight and changes in weight and plasma estradiol were examined in relation to the TTTAn polymorphism. Results Mean age was 46.5 ± 10.82 years, and BMI was 47.1 ± 8.46 kg/m2. The most common repeats were 7 and 11. TTTAn number did not correlate to plasma estradiol in the univariate analysis. When patients were stratified per weight groups, the correlation between plasma estradiol and weight was seen only among men with higher TTTA repeat at baseline and two years. Similarly, only men with higher TTTA exhibited reduced estradiol levels after weight loss. Conclusion Higher TTTA repeat are associated with a strengthened relationship between obesity and estradiol. The well established effect of increased weight on plasma estradiol appears to be absent in men with low TTTA numbers.

Obesity and male hypogonadism: Tales of a vicious cycle

“…In fact, a recent study by Ghanim et al reported that hypogonadal diabetic men's adipocytes expressed less aromatase and oestrogen receptor alpha when compared with eugonadal diabetic men. Additionally, Hammoud et al described an aromatase polymorphism that positively correlated with elevated circulating estradiol and body weight. Interestingly, only men who exhibited the polymorphism had estradiol levels reduced after weight loss.…”

Estrogens and Body Weight Regulation in Men

“…(Schneider et al, 1979),(MacDonald et al, 2010) The reasons for this variable co-occurrence of obesity and hyperestrogenemia in men are not well defined but may include repeat number of a TTTA polymorphism in the aromatase gene CYP19A1 . (Hammoud et al, 2010) Although overtly elevated serum estrogen levels are not found in all men with obesity, it has been proposed that obesity also may represent a state of relative rather than absolute estrogen excess. Thus, increased peripheral aromatization of testosterone in obese men may lead to enhanced central estradiol signaling that suppresses gonadotropin production and contributes to a sustained state of hypogonadotropic hypogonadism.…”

Testosterone-Induced Effects on Lipids and Inflammation

“…High levels of estrogens in obese males result from the increased conversion of androgens to estrogens, owing to the high bioavailability of these aromatase enzymes [23]. Hammoud et al [24] recently discovered that an aromatase polymorphism modulates the relationship between weight and E2 levels in obese men. Abdominal or visceral fat is more likely to lead to changes in hormone levels and to cause inflammation than fat stored in other parts of the body [25].…”