Context: In men, circulating 17β-estradiol (E2) originates primarily from aromatization of testosterone (T) in peripheral tissues, particularly adipose tissue. The effect of ageing and obesity on circulating E2 remains unclear.
Objective: To investigate 5-year changes in serum E2 and the association with T and fat mass in Australian men.
Design: Participants were 725 community-dwelling men, aged 35 years and older, without established disease of, or medications affecting, the hypothalamus-pituitary-gonadal axis. At baseline and 5-year follow-up, socio-demographic and health-related data including behaviours, chronic conditions, and medication use were collected by questionnaire. E2 and T were assayed by liquid chromatography-tandem mass spectrometry and Sex hormone-binding globulin (SHBG) by immunofluorescence assay.
Separately, we determined the effect of 28 days over-feeding a high fat energy dense diet on adipose tissue aromatase mRNA measured by qPCR in 8 male volunteers (mean age 35.4 ± 7.8 years, BMI 26.1 ± 3.8 kg/m2).
Anthropometry and fat mass were assessed clinically and by dual-energy X-ray absorptiometry respectively, in both studies.
Results: At baseline, mean age was 53.0 ± 10.8 years. Mean serum E2 levels at baseline and follow-up were 94.9 ± 34.8 and 89.4 ± 30.4 pmol/L respectively (-1.1 pmol/L/year). On multivariate analyses, E2 change was associated with T change (p˂0.001) but not age or percentage total fat mass. Changes in T and T/E2 ratio were inversely associated with change in fat mass (p=0.003 and 0.012 respectively). The change in T/E2 was consistent across fat mass quartiles.
Overfeeding increased fat mass but not aromatase mRNA expression in abdominal subcutaneous fat.
Conclusion: Circulating E2 levels are primarily dependent on T. With increasing fat mass, E2 decreases less than T, likely due to the greater overall aromatase activity despite no increase in aromatase expression.