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Context  In men, circulating 17β-estradiol originates primarily from peripheral aromatization of testosterone particularly in adipose tissue. The effect of ageing and obesity on circulating estradiol remains unclear.    Objective  Determine five-year changes in serum estradiol and the association with testosterone and fat mass in Australian men.    Design  Longitudinal cohort study. At baseline and five-year follow-up, socio-demographic and health-related data including behaviors, chronic conditions, and medication use were collected by questionnaire. Estradiol and testosterone were assayed by liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin by immunochemiluminescent assay. Fat mass was assessed by dual-energy X-ray absorptiometry.    Participants  Community-dwelling men aged 35 years and older at enrollment, resident in the northern and western suburbs of Adelaide without established disease of, or medications affecting, the hypothalamus-pituitary-gonadal axis (n = 725).    Main outcome measures  The dependence of change in serum estradiol over five years on age, testosterone and fat mass after adjustment for multiple confounders.    Results  At baseline, mean age was 53.0 ± 10.8 years. Mean serum estradiol levels at baseline and five-year follow-up were 94.9 ± 34.8 and 89.4 ± 30.4 pmol/L respectively (-1.1 pmol/L/year). On multivariable analyses, estradiol change was associated with changes in testosterone (B-estimate = 2.719, standard error = 0.369, p˂0.001), but not age or total fat mass. Change in testosterone/estradiol ratio was inversely associated with change in fat mass (B = -1.450, SE = 0.575, p = 0.012), and this was consistent across quartiles of fat mass change.    Conclusions  In healthy men, circulating estradiol is primarily dependent on testosterone. With increasing fat mass, estradiol decreases less than testosterone. From a clinical standpoint these data indicate that obesity is associated with a change in the testosterone to estradiol ratio, but a change in estradiol does not occur unless some other pathology is present.

Age-related changes in estradiol and longitudinal associations with fat mass in men