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Progesterone increases plasma volume independent of estradiol

¹The John B. Pierce Laboratory, and Departments of ²Epidemiology & Public Health and ³Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Submitted 7 January 2005 ; accepted in final form 15 February 2005

Adequate plasma volume (PV) and extracellular fluid (ECF) volume are essential for blood pressure and fluid regulation. We tested the hypotheses that combined progesterone (P₄)-estrogen (E₂) administration would increase ECF volume with proportional increases in PV, but that P₄ would have little independent effect on either PV or ECF volume. We further hypothesized that this P₄-E₂-induced fluid expansion would be a function of renin-angiotensin-aldosterone system stimulation. We suppressed P₄ and E₂ with a gonadotropin-releasing hormone (GnRH) antagonist in eight women (25 ± 2 yr) for 16 days; P₄ (200 mg/day) was added for days 5–16 (P₄) and 17-estradiol (2 x 0.1 mg/day patches) for days 13–16 (P₄-E₂). On days 2 (GnRH antagonist), 9 (P₄), and 16 (P₄-E₂), we estimated ECF and PV. To determine the rate of protein and thus water movement across the ECF, we also measured transcapillary escape rate of albumin. In P₄, increased from 2.5 ± 1.3 to 12.0 ± 2.8 ng/ml (P < 0.05) with no change in (21.5 ± 9.4 to 8.6 ± 2.0 pg/ml). In P₄-E₂, plasma concentration of P₄ remained elevated (11.3 ± 2.7 ng/ml) and plasma concentration of E₂ increased to 254.1 ± 52.7 pg/ml (P < 0.05). PV increased during P₄ (46.6 ± 2.5 ml/kg) and P₄-E₂ (48.4 ± 3.9 ml/kg) compared with GnRH antagonist (43.3 ± 3.2 ml/kg; P < 0.05), as did ECF (206 ± 19, 244 ± 25, and 239 ± 27 ml/kg for GnRH antagonist, P₄, and P₄-E₂, respectively; P < 0.05). Transcapillary escape rate of albumin was lowest during P₄-E₂ (5.8 ± 1.3, 3.5 ± 1.7, and 2.2 ± 0.4%/h for GnRH antagonist, P₄, and P₄-E₂, respectively; P < 0.05). Serum aldosterone increased during P₄ and P₄-E₂ compared with GnRH antagonist (79 ± 17, 127 ± 13, and 171 ± 25 pg/ml for GnRH antagonist, P₄, and P₄-E₂, respectively; P < 0.05), but plasma renin activity and plasma concentration of ANG II were only increased by P₄-E₂. This study is the first to isolate P₄ effects on ECF; however, the mechanisms for the ECF and PV expansion have not been clearly defined.

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

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