Effects of estrogen and progesterone administration on extracellular fluid

Abstract

To determine the effect of estrogen and progesterone on plasma volume (PV) and extracellur fluid volume (ECFV), we suppressed endogenous estrogen and progesterone by using the gonadotropin-releasing hormone (GnRH) antagonist ganirelix acetate in seven healthy women (22 ± 1 yr). Subjects were administered GnRH antagonist for 16 days. Beginning on day 5 of GnRH antagonist administration, subjects were administered estrogen (E2) for 11 days, and beginning on day 12 of GnRH antagonist administration, subjects added progesterone (E2-P4) for 4 days. On days 2, 9, and 16 of GnRH antagonist administration, we estimated ECFV (inulin washout), transcapillary escape rate of albumin (TERalb), and PV (Evans blue dye). Plasma E2concentration increased from 17.9 ± 4.5 (GnRH antagonist) to 195.9 ± 60.1 (E2, P < 0.05) to 245.6 ± 62.9 pg/ml (E2-P4, P < 0.05). Compared with GnRH antagonist (1.3 ± 0.5 ng/ml), plasma P4concentration was unchanged during E2(0.9 ± 0.3 ng/ml) and increased to 9.4 ± 3.1 ng/ml during E2-P4( P < 0.05). Both E2(44.1 ± 3.1 ml/kg) and E2-P4(47.7 ± 2.8 ml/kg) increased PV compared with GnRH antagonist (42.8 ± 1.3 ml/kg, P < 0.05). Within-subjects TERalbwas a strong negative predictor of PV (mean r = 0.92 ± 0.03, P < 0.05), and TERalbwas lowest during E2-P4(5.7 ± 0.5, 4.1.0 ± 1.1, and 2.8 ± 0.9%/h, P < 0.05, for GnRH antagonist, E2, and E2-P4, respectively). ECFV was reduced during E2(227 ± 31 ml/kg, P < 0.05) compared with both GnRH antagonist (291 ± 37 ml/kg) and E2-P4(283 ± 19 ml/kg). Thus the percentage of extracellular fluid in the plasma compartment increased to 21.0% ( P < 0.05) during E2compared with GnRH antagonist (16.1%) and E2-P4(17.2%) admistration. Thus E2increased PV via actions on the capillary endothelium to lower TERalband favor intravascular water retention, whereas during E2-P4PV increased via the combined responses of ECFV expansion and lower TERalb.