Regulation of energy expenditure by estradiol in premenopausal women

Suppressing sex hormones in women for 1 wk reduces resting energy expenditure (REE). The effects of more chronic suppression on REE and other components of total energy expenditure (TEE), and whether the reduction in REE is specifically due to loss of estradiol (E-2), are not known. We compared the effects of 5 mo of sex hormone suppression (gonadotropin releasing hormone agonist therapy, GnRH(AG)) with placebo (PL) or E-2 add-back therapy on REE and the components of TEE. Premenopausal women received GnRH(AG) (leuprolide acetate 3.75 mg/mo) and were randomized to receive transdermal therapy that was either E-2 (0.075 mg/d; n = 24; means +/- SD, aged = 37 +/- 8 yr, BMI = 27.3 +/- 6.2 kg/m(2)) or placebo (n = 21; aged = 34 +/- 9 yr, BMI = 26.8 +/- 6.2 kg/m(2)). REE was measured by using a metabolic cart, and TEE, sleep EE (SEE), exercise EE (ExEE, 2 X 30 min bench stepping), non-Ex EE (NExEE), and the thermic effect of feeding (TEF) were measured by using whole room indirect calorimetry. REE decreased in GnRH(AG) + PL [mean (95% CI), -54 (-98, -15) kcal/d], but not GnRH(AG) + E-2 [+ 6 (-33, +45) kcal/d] (difference in between-group changes, P = 0.05). TEE decreased in GnRH(AG) + PL [-128 (-214, -41) kcal/d] and GnRH(AG) + E-2 [-96 (-159, -32) kcal/d], with no significant difference in between-group changes (P = 0.55). SEE decreased similarly in both GnRH(AG) + PL [-0.07 (-0.12, -0.03) kcal/min] and GnRH(AG) + E-2 [-0.07 (-0.12, -0.02) kcal/min]. ExEE decreased in GnRH(AG) + PL [-0.46 (-0.79, -0.13) kcal/min], but not GnRH(AG) + E-2 [- 0.30 (-0.65, +0.06) kcal/min]. There were no changes in TEF or NExEE in either group. In summary, chronic pharmacologic suppression of sex hormones reduced REE and this was prevented by E-2 therapy.