The effects of synthetic estrogens on the metabolic clearance and production rates of estrone and estradiol

Abstract

The metabolic clearance rates (MCR) of estrone (1) and estradiol were determined by pulse injections and constant infusions of 3H-estrone and 3H-estradiol in seven women taking mestranol-containing compounds and in seven women taking ethinyl estradiol-containing compounds. These results were compared with the results previously obtained in our laboratory (2, 3, 4, 5) in comparable women not taking these compounds. In the women taking mestranol the mean (± SE) MCR for estradiol, 750 ± 600 1/day/m 2, was similar to our normal mean value, 790 ± 30 1/day/m 2. However, the mean MCR for estrone was less 1,010 ± 60 1/day/m 2 than that in normals 1,230 ± 30 1/day/m 2. In the women taking ethinyl estradiol the mean MCR for estradiol, 1,070 ± 60 1/day/m 2 was significantly ( P < 0.01) greater than the normal value. The mean MCR for estrone, 1,180 ± 80 1/day/m 2 was not different from the normal. Using an immunoassay to measure the concentrations of estradlol and. estrone in plasma, the mean level of estradlol in mestranol users was 40 ± 7 Pg/ml and in ethinyl estradlol users 69 ± 4 pg/ml. The mean calculated production rate for estradlol in the mestranol users was 47 ± 8 μg/day and in the ethinyl estradlol users was 120 ± 22 μg/day. The mean calculated, production rates for estrone were 71 ± 12 and 93 ± 12 μg/day in the respective groups. Thus while mestranol appears to have little effect on endogenous estrogen metabolism, the use of ethinyl estradiol appears to increase the MCR of estradlol, but not of estrone. The MCR of estradlol returns to the normal range when ethinyl estradlol is stopped.