Estrogen replacement in postmenopausal women: are we currently overdosing our patients?

As there are no proven optimal serum estradiol levels, we sought to evaluate the pharmacokinetic profiles of serum estradiol levels following a single oral dose of 2 mg estradiol and 1 mg of estriol (Trisequens) among 26 surgically induced, postmenopausal patients. Their serum estradiol levels were periodically measured over 24 h following oral administration of the drug. They were divided into two groups according to the computed hourly mean estradiol values: group A, < 250 pg/ml/h ( < 918 pmol/l/h) and group B, > 250 pg/ml/h ( > 918 pmol/l/h). The mean peak estradiol concentrations were noted 2 h after drug administration and amounted to 595 +/- 190 pg/ml (2,184 +/- 697 pmol/l) in the entire cohort; 435 +/- 117 pg/ml (1,597 +/- 430 pmol/l) in group A and 712 +/- 142 pg/ml (2,614 +/- 521 pmol/l) in group B (p < 0.001). The mean total area under the curve in group A was 4,887 pg/ml (17,940 pmol/l), which was significantly lower than that of 7,995 +/- 652 pg/ml/24 h (29,350 +/- 2,393 pmol/l/24 h) found for group B (p < 0.001). The mean body mass index showed a significant difference (p < 0.003) between group A and group B (29.4 +/- 0.56 vs. 24.3 +/- 0.24). We found that 57% of our patients were exposed to excessively high levels of estradiol during the 24-hour period following drug ingestion. We advise monitoring estradiol levels and individualizing estrogen replacement therapy, to avoid the long-term exposure of postmenopausal patients to superphysiological estradiol levels.