The effects of ethinylestradiol (1 mug/kg body weight daily) on plasma renin substrate concentration, other factors of the renin-aldosterone-system, and on the cortisol-binding capacity of transcortin were determined in 8 young men and 9 young women. The absolute and relative elevation of plasma renin substrate after 5, 14, and 24 days of ethinylestradiol administration was significantly (P less than 0.001) greater in females than males. Control and posttreatment transcortin levels were also higher in women than men, but the percentage increase did not differ between males and females. It is likely that sex differences in the response of plasma renin substrate to the estrogen are due to differences in hepatic synthesis and/or release of renin substrate. In females, plasma renin activity, angiotensin II concentration, and urinary aldosterone excretion rose significantly although less markedly than plasma renin substrate concentration, while in males only the increase in plasma angiotensin II concentration was significant. These results indicate that no safe conclusions on metabolic effects of estrogen treatment in women can be drawn from experiments carried out in male subjects.
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