1. The effects on the serum electrolytes of long-term treatment with either mestranol or a placebo were determined in 175 healthy middle-aged oophorectomized women. In forty of these women the packed cell volume (PCV), serum albumin, serum and urinary osmolality, inulin space and total exchangeable sodium (Nae) were also measured.
2. The mean serum sodium and chloride concentrations were significantly lower in the mestranol-treated women, and this was associated with a significant reduction in the mean PCV and the mean serum albumin concentration by comparison with the placebo-treated group.
3. The mean urinary osmolality was higher and the mean serum osmolality lower in the mestranol group such that there was a significant increase in the mean urine/serum osmolality ratio as compared with the placebo group.
4. The mean inulin space was significantly higher in the mestranol group as compared with the controls, but there was no significant difference in Nae.
5. These findings support the hypothesis that oestrogen-induced fluid retention is the result of primary water retention with secondary redistribution of body sodium.