To test the hypothesis that progesterone, independent of estrogen, decrease
s the plasma osmotic threshold for arginine vasopressin (AVP) release and t
hirst onset, we compared AVP and thirst responses to hypertonic saline infu
sion (HSI) during administration of oral contraceptives (OCs) containing pr
ogesterone (OCP) with responses to infusion of OCs containing progesterone
and estrogen (OCEP). Eight women (29 +/- 2 yr) were infused with 3% NaCl (1
20 min, 0.1 ml.kg body wt(-1).min(-1)) and consumed fluid (90 min, 15 ml/kg
body wt) in the early follicular and midluteal phases of a 28-day menstrua
l cycle and also after 4 wk of OCP and after 4 wk of OCEP in a randomized c
rossover design. Baseline plasma osmolality (P-osm) was lower in the luteal
phase (280 +/- 1 mosmol/kgH(2)O) and during OCEP (283 +/- 1 mosmol/kgH(2)O
) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, P < 0.05) but was
unaffected by OCP (284 +/- 1 mosmol/kgH(2)O). P-osm remained lower in the
follicular phase than in the luteal phase and with OCEP throughout the firs
t 50 min of HSI. The mean abscissal plasma AVP concentration-P-osm intercep
t was unaffected by OCP (267 +/- 1 mosmol/kgH(2)O) but was greater in the f
ollicular phase (273 +/- 2 mosmol/kgH(2)O) than in the luteal phase (266 +/
- 4 mosmol/kgH(2)O) and with OCEP (268 +/- 2 mosmol/kgH(2)O, P < 0.05). The
re were no differences in osmotic thresholds for thirst onset across experi
mental days. Despite the lower osmotic threshold for AVP release during the
luteal phase and with OCEP, fluid balance, renal free water clearance, and
Na+ regulation during HSI were unaffected by menstrual phase or OC treatme
nt, indicating a lower osmotic operating point for body water balance. OCP
did not affect osmotic AVP regulation, suggesting that progesterone does no
t affect osmotic fluid regulation through a mechanism independent of estrog
en.