Exogenous oestradiol and progesterone administration does not cause oedema in healthy young women

Oedema is an increase in the extravascular component of extracellular fluid volume (ECFV). Fluid movement across the ECF is controlled by hydrostatic and oncotic pressures, which are influenced by oestradiol and progesterone. Thus we hypothesized that oestradiol decreases, while combined oestradiol + progesterone increases, protein and fluid movement out of the vasculature.

Subjects were eight healthy women (22 +/- 2 years).

Oestrogens and progesterone were suppressed with a gonadotropin-releasing hormone antagonist for 16 days; oestradiol (2 x 0.1 mg/day patches) was added for days 5-16 (E(2)) and progesterone (200 mg/day) was added for days 13-16 (E(2)-P(4)).

We estimated intravascular (plasma) volume (PV), transcapillary albumin escape rate (TER(alb)), and Starling forces (hydrostatic pressures of plasma and interstitium, plasma colloid pressure, capillary filtration coefficient) in the forearm on days 2 (GnRH antagonist), 9 (E(2)) and 16 (E(2)-P(4)).

In E(2), P([E2]) increased from 85 +/- 26 to 984 +/- 136 pmol/ml (P < 0.05), with no change in P([P4]). In E(2)-P(4), P([E2]) increased to 775 +/- 195 pmol/ml and P([P4]) increased from 6.4 +/- 3.2 to 43.8 +/- 16.2 nmol/l, P < 0.05). TER(alb) was lower during E(2) (5.1 +/- 0.9) and E(2)-P(4) (5.0 +/- 1.1) compared to GnRH antagonist (5.8 +/- 0.9%/h, P < 0.05). Plasma volume was unchanged by E(2), and showed a trend (P = 0.07) for an increase during E(2)-P(4) (48.2 +/- 2.9, 49.0 +/- 3.0 and 53.9 +/- 3.5 ml/kg for GnRH antagonist, E(2), E(2)-P(4), respectively). Starling forces were unaffected by hormone treatments. Plasma renin activity and serum aldosterone concentration increased during E(2)-P(4).

Neither E(2) nor E(2)-P(4) altered TER(alb) sufficiently to impact Starling forces indicating neither E(2) nor P(4) administration at these levels would likely cause oedema.