Effects of oral contraceptives on body ﬂuid regulation

R. Nadel. Effects of oral contraceptives on body ﬂuid regulation. J. Appl. Physiol. 87(3): 1016–1025, 1999. —To test the hypothesis that estrogen reduces the operating point for osmoregulation of arginine vasopressin (AVP), thirst, and body water balance, we studied nine women (25 6 1 yr) during 150 min of dehydrating exercise followed by 180 min of ad libitum rehydration. Subjects were tested six different times, during the early-follicular (twice) and midluteal (twice) menstrual phases and after 4 wk of combined [estradiol-norethindrone (progestin), OC E 1 P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (P osm ) was lower in the luteal phase (281 6 1 mosmol/kgH 2 O, combined means, P , 0.05), OC E 1 P (281 6 1 mosmol/kgH 2 O, P , 0.05), and OC P (282 6 1 mosmol/kgH 2 O, P , 0.05) than in the follicular phase (286 6 1 mosmol/kgH 2 O, combined means). High plasma estradiol concentration lowered the P osm threshold for AVP release during the luteal phase and during OC E 1 P [ x -intercepts, 282 6 2, 278 6 2, 276 6 2, and 280 6 2 mosmol/kgH 2 O, for follicular, luteal (combined OC E 1 P, and OC P, respectively; P , 0.05, luteal and OC E 1 P vs. follicular phase] during exercise dehydration, and 17 b -estradiol administration lowered the P osm threshold for thirst stimulation [ x -intercepts, 280 6 2, 279 6 2, 276 6 2, and 280 6 2 mosmol/kgH 2 O for follicular, luteal, OC E 1 P, and OC P, respectively; P , 0.05, OC E 1 P vs. follicular phase], without affecting body ﬂuid balance. When plasma 17 b -estradiol concentration was high, P osm was low throughout rest, exercise, and rehydration, but plasma arginine vasopressin concentration, thirst, and body ﬂuid retention were unchanged, indicating a lowering of the osmotic operat- ing point for body ﬂuid regulation. Separate repeated-measures ANOVA models were performed to test differences in the dependent and E or P administration. Bonferroni’s t was used to correct for multiple comparisons where appropriate. Pearson’s product moment correlation was used to assess the relationship of P [AVP] as a function of P osm on individual data during exercise, and the abscissal intercepts deﬁned the ‘‘theoretical osmotic threshold’’ for AVP release (8). We used repeated-measures ANOVA models, followed by Bonferroni’s t -test, to test differences in the abscissal intercepts and slopes due to menstrual phase or oral contraceptive treatment (4, 8). On the basis of an a -level of 0.05 and a sample size of 8, our b -level (power) was $ 0.80 for detecting effect sizes of 2.0 pg/ml, 0.67 ml/min, 2.0 ng·ml ANG 2 1 ·h 2 1 , 40 pg/ml, 10 pg/ml, and 3.0 meq for P [AVP] , renal free water clearance, PRA, P [ald] , P [ANP] , and renal Na 1 excretion, respectively (4, 7, 8, 28). Data were analyzed using BMDP statistical software (BMDP Statistical Software, CA) and expressed as means 6 SE. Anginine vasopressin plasma concentration (P [AVP] ), cognitive thirst ratings, and plasma volume (PV) (estimated percent change from preexercise value) were measured at rest and in response to dehydrating exercise and 180 min of ad libitum rehydration in follicular and luteal phases and during OC E 1 P ( n 5 8) and OC P ( n 5 9).