Journal of Applied Physiology
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J Appl Physiol 87: 1016-1025, 1999;
8750-7587/99 $5.00
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Vol. 87, Issue 3, 1016-1025, September 1999

Effects of oral contraceptives on body fluid regulation

Nina S. Stachenfeld, Celso Silva, David L. Keefe, Cheryl A. Kokoszka, and Ethan R. Nadeldagger

The John B. Pierce Laboratory, Department of Epidemiology and Public Health, and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06519; and Women and Infants Hospital, Brown University School of Medicine, Providence, Rhode Island 02905

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 ± 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 + P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (Posm) was lower in the luteal phase (281 ± 1 mosmol/kgH2O, combined means, P < 0.05), OC E + P (281 ± 1 mosmol/kgH2O, P < 0.05), and OC P (282 ± 1 mosmol/kgH2O, P < 0.05) than in the follicular phase (286 ± 1 mosmol/kgH2O, combined means). High plasma estradiol concentration lowered the Posm threshold for AVP release during the luteal phase and during OC E + P [x-intercepts, 282 ± 2, 278 ± 2, 276 ± 2, and 280 ± 2 mosmol/kgH2O, for follicular, luteal (combined means), OC E + P, and OC P, respectively; P < 0.05, luteal phase and OC E + P vs. follicular phase] during exercise dehydration, and 17beta -estradiol administration lowered the Posm threshold for thirst stimulation [x-intercepts, 280 ± 2, 279 ± 2, 276 ± 2, and 280 ± 2 mosmol/kgH2O for follicular, luteal, OC E + P, and OC P, respectively; P < 0.05, OC E + P vs. follicular phase], without affecting body fluid balance. When plasma 17beta -estradiol concentration was high, Posm 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 operating point for body fluid regulation.

estrogen; progesterone; rehydration; osmolality; arginine vasopressin


dagger Deceased




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