The Effects of Estradiol and Progesterone on Arginine Vasopressin Regulation and Serum Sodium Concentration
Condition: Exercise Induced Hyponatremia
MeSH terms: Diabetes Insipidus; Hyponatremia
Study type: Interventional

Summary: 
      Women are at greater risk for exercise-induced hyponatremia (low blood sodium concentration)
      and this risk has been attributed to their lower body weight and size, excess water ingestion
      and longer racing times relative to men. While these factors contribute to the greater
      incidence of hyponatremia in women, it is likely that their greater levels of estradiol in
      plasma and/or tissue also play a role in increasing the risk of hyponatremia in women. More
      importantly, estradiol may also leave women more susceptible to the extreme consequences of
      hyponatremia (i.e. brain damage, death). Hyponatremia is generally attributed to
      inappropriately elevated levels of the hormone arginine vasopressin (AVP). AVP is the most
      important hormone controlling water retention in the kidney. Earlier studies in our
      laboratory have demonstrated that estradiol lowers the threshold for thirst sensation and AVP
      release during exercise. The purpose of these studies is to test the hypotheses that in women
      with a history of hyponatremia, estradiol lowers the thresholds for thirst and AVP release,
      leading to greater fluid retention, lower blood sodium concentration during endurance
      exercise in the heat. However, we further hypothesize that progesterone administration along
      with estradiol administration will attenuate the effect of estradiol on the regulation of
      thirst and AVP, normalize fluid retention, and serum sodium concentration during endurance
      exercise in the heat. In women without a history of hyponatremia, we expect that estradiol
      administration will lower the thresholds for thirst and AVP release, but will not increase
      fluid retention or reduce blood sodium concentration during endurance exercise in the heat.
      We hypothesize that progesterone administration along with estradiol administration will
      attenuate the effect of estradiol on thirst and AVP, but have no effect on fluid retention or
      serum sodium concentration during endurance exercise in the heat. To test these hypotheses,
      women will perform endurance exercise in the heat under three hormonal conditions: 1) during
      Gonadotropin-releasing hormone (GnRH) antagonist alone--which will suppress estradiol and
      progesterone; 2) during GnRH antagonist+estradiol; and 3) during GnRH antagonist+estradiol+
      progesterone. During exercise, fluid will be replaced with either water or a
      carbohydrate-electrolyte beverage (random assignment).
    


Intervention name(s): Gatorade Endurance Formula; ganirelix acetate
Intervention type(s): Dietary Supplement; Other
Intervention description(s): carbohydrate electrolyte beverage; GnRH antagonist, subcutaneous injection, 0.25 mg/day for 21 days.
Other intervention name(s): Antagon
Intervention MeSH terms: Ganirelix
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science