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J Appl Physiol 96: 1011-1018, 2004. First published December 5, 2003; doi:10.1152/japplphysiol.01032.2003
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Effects of estrogen and progesterone administration on extracellular fluid

Nina S. Stachenfeld and Hugh S. Taylor

Departments of Epidemiology and Public Health, and Obstetrics and Gynecology, Division of Reproductive Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06519

Submitted 24 September 2003 ; accepted in final form 21 November 2003

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 E2 concentration 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 P4 concentration 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 TERalb was a strong negative predictor of PV (mean r = 0.92 ± 0.03, P < 0.05), and TERalb was 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 E2 compared with GnRH antagonist (16.1%) and E2-P4 (17.2%) admistration. Thus E2 increased PV via actions on the capillary endothelium to lower TERalb and favor intravascular water retention, whereas during E2-P4 PV increased via the combined responses of ECFV expansion and lower TERalb.

extracellular fluid regulation; gonadotropin-releasing hormone antagonist; ganirelix acetate; blood volume; plasma volume


Address for reprint requests and other correspondence: N. S. Stachenfeld, The John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06519 (E-mail: nstach{at}jbpierce.org).




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