Short-term 17β-estradiol decreases glucose Ra but not whole body metabolism during endurance exercise

The female sex hormone 17beta-estradiol (E(2)) has been shown to increase lipid and decrease carbohydrate utilization in animals. We administrated oral E(2) and placebo (randomized, double blind, crossover) to eight human male subjects for 8 days ( approximately 3 mg/day) and measured respiratory variables, plasma substrates, hormones (E(2), testosterone, leptin, cortisol, insulin, and catecholamines), and substrate utilization during 90 min of endurance exercise. [6,6-(2)H]glucose and [1,1,2,3,3-(2)H]glycerol tracers were used to calculate substrate flux. E(2) administration increased serum E(2) (0.22 to 2.44 nmol/l, P < 0.05) and decreased serum testosterone (19.4 to 11.5 nmol/l, P < 0.05) concentrations, yet there were no treatment effects on any of the other hormones. Glucose rates of appearance (R(a)) and disappearance (R(d)) were lower, and glycerol R(a)-to-R(d) ratio was not affected by E(2) administration. O(2) uptake, CO(2) production, and respiratory exchange ratio were not affected by E(2); however, there was a decrease in heart rate (P < 0.05). Plasma lactate and glycerol were unaffected by E(2); however, glucose was significantly higher (P < 0. 05) during exercise after E(2) administration. We concluded that short-term oral E(2) administration decreased glucose R(a) and R(d), maintained plasma glucose homeostasis, but had no effect on substrate oxidation during exercise in men.