We hypothesized that exercise-associated hyponatremia (EAH) is a function of excess sodium loss combined with high water intake in women at risk for dysnatremias during endurance exercise. We further hypothesized that estradiol and progesterone exposure increases fluid retention and sodium loss during exercise in women at risk for EAH. For 16 days we suppressed estrogens and progesterone with a gonadotropin-releasing hormone antagonist (GnRH ant) in seven women with (Hypo) and nine women without (no Hypo) a history of hyponatremia; we added 17beta-estradiol (0.2 mg/day patches) for days 4-16 (E(2)) and progesterone (200 mg/day) for days 13-16 (E(2)-P(4)). Under each hormone condition, subjects cycled in 35 degrees C at 65% peak oxygen consumption (Vo(2peak)) for 60 min, then at 55-60% Vo(2peak) for 120 min. Subjects drank 8 ml/kg of water (and replenished urine volume) every 30 min over the final 120 min of exercise. S([Na+]) fell by 4.3, 3.9, and 3.1 meq/l (P < 0.05) with drinking during GnRH ant, E(2), and E(2)-P(4) in Hypo, with little fall in no Hypo. Under all conditions, combined urine and sweat sodium loss were similar between Hypo [-85.6 (SD 36.2), -86.4 (SD 39.2), and -112.0 (SD 30.0) meq] and no Hypo [-98.0 (SD 54.8), -80.9 (SD 57.6), and -105.1 (SD 46.4) meq, for GnRH, E2, and E2-P4], as was mass balance of electrolytes (E(MB)) for Hypo [-104.8 (SD 32.8), -103.6 (SD 42.1), and -132.8 (SD 34.9) meq] compared with no Hypo [-128.8 (SD 57.2), -113.5 (SD 61.1), and -143.4 (SD 49.6) meq for GnRH, E2, and E2-P4]. Mass balance of water [V(MB), for Hypo, 0.42 (SD 0.10), 0.62 (SD 0.25), and -0.11 (SD 0.11) liter] compared with no Hypo [0.01 (SD 0.15), 0.03 (SD 17), and -0.16 (SD 0.13) liter for GnRH, E2, and E2-P4, P < 0.05] indicates water retention was the primary contributor to the lower S([Na+]) in Hypo women.