Pharmacokinetics of oral micronized β-estradiol in postmenopausal women receiving maintenance hemodialysis

Abstract

Background. Although 11% of postmenopausal women with end-stage renal disease (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use remains poorly explored. Although there remains controversy surrounding the benefits of HRT, it may be of particular interest in this population, which has a high risk of bone loss and a fourfold increase in fracture risk compared to the general population. However, the appropriate dose of estrogen for use in postmenopausal women with ESRD is not known. The objective of this study was to evaluate the steady-state pharmacokinetics of oral micronized β-estradiol in postmenopausal women with ESRD compared with postmenopausal women with normal renal function in order to determine equivalent dosing. Methods. Six postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy postmenopausal controls received 14 days of micronized β-estradiol (1.0 mg for control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone binding globulin (SHBG) concentrations were determined. Free estradiol concentrations were calculated using a previously described method. Results. Women with ESRD had significantly lower serum albumin (61.0 ± 31 mol/L vs. 684 ± 83 μmol/L) and SHBG (78 ± 17 vs. 118 ± 13 nmol/L) than control subjects. Total clearance of estradiol was not significantly different. Due to difference in binding, free estradiol concentrations were significant higher in ESRD women (53.2 ± 17.7 pg/mL) than control women (43.5 ± 8.7 pg/mL), despite receiving 50% of the dose. There was no significant difference in estrone concentrations. Clearance of both estradiol and estrone in the dialysate was minimal. Conclusion. Women with ESRD should receive approximately 50% of the dose typically prescribed to women without ESRD.