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1 The John B. Pierce Laboratory, New Haven, CT, USA; Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
2 Reproductive Endocrinology, Yale University School of Medicine, New Haven, CT, USA
* To whom correspondence should be addressed. E-mail: nstach{at}jbpierce.org.
To determine the effect of estrogen and progesterone on plasma volume (PV) and extracellur fluid distribution (ECFV), we suppressed endogenous estrogen and progesterone using the gonadotropin releasing-hormone (GnRH) antagonist, ganirelix acetate in 7 healthy women (22±1 yr). Subjects administered GnRH antagonist for16 days. Beginning on day five of GnRH antagonist administration, subjects administered estrogen (E2) for 11 days, and beginning on day 12 of GnRH antagonist administration, subjects added progesterone (E2-P4) for four 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] increased from 17.9±4.5 pg/ml (GnRH antagonist) to 195.9±60.1 pg/ml (E2, P < 0.05) to 245.6±62.9 pg/ml (E2-P4, P < 0.05). Compared to GnRH antagonist (1.3±0.5 ng/ml), plasma [P4] 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 to 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 %/hr, P < 0.05 for GnRH antagonist, E2 and E2-P4, respectively). ECFV was reduced during E2 (227±31 ml/kg, P < 0.05) compared to both GnRH antagonist (291±37) 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 to GnRH antagonist (16.1 %) and E2-P4 (17.2 %). Thus E2 increased PV via actions on the capillary endothelium to lower TERalb and favor intravascular water retention, while during E2-P4 PV increased via the combined responses of ECFV expansion and lower TERalb.
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