Effects of estradiol on substrate turnover during exercise in amenorrheic females

The purpose of this investigation was to determine the effects of transdermal estradiol (E2) replacement on substrate utilization during exercise. Amenorrheic females (N = 6) performed three exercise trials following 72 h of placebo (C 72) and 72 and 144 h of medicated transdermal estradiol (E2) treatment (E2 72 and E2 144). Exercise involved 90 min of treadmill running at 65% V̇O(2max) followed by timed exercise to exhaustion at 85% V̇O(2max). Resting blood samples were obtained for glucose, insulin, free fatty acids (FFA), and E2. Exercise blood samples were obtained for E2, lactate, epinephrine, and norepinephrine. Rates of appearance and disposal were calculated for glucose and glycerol using a primed, continuous infusion of [6,6-²H] glucose and [²H₅] glycerol. Medicated transdermal placement increased E2 significantly at rest, before exercise (35.03 ± 12.3, 69.5 ± 20.1, and 73.1 ± 31.6 pg·mL^-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Resting FFA increased significantly following E2 treatment (0.28 ± 0.16, 0.41 ± 0.27, and 0.40 ± 0.21 mmol·L^-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Glucose Ra was significantly decreased during exercise as a result of E2 replacement (21.9 ± 7.7, 18.9 ± 6.2, and 18.9 ± 5.6 μmol·kg^-1·min^-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Average glucose Rd also decreased during exercise as a result of E2 replacement (21.3 ± 7.8, 18.5 ± 6.4, and 18.6 ± 5.8 μmol·kg^-1·min^-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). However, the estimated relative contribution of plasma glucose and muscle glycogen to total carbohydrate oxidation was similar among the trials. Epinephrine values were significantly lower late in exercise during the E2 72 and E2 144 trials, compared with the C 72 trial (P < 0.05). These results indicate that elevated E2 levels can alter glucose metabolism at rest and during moderate intensity exercise as a result of decreased gluconeogenesis, epinephrine secretion, and/or glucose transport.