Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E(2)) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E(2), estrone (E(1)), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E(2) dose under identical conditions. At baseline, total and free E(2) levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E(2), total and free E(2) levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P less than or equal to 0.05). After 1 mg oral E(2), total serum E(2) peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E(2) treatment, total serum E(2) peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E(1) was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E(2), E(1) concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E(1) concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E(2), with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E(2) levels are higher in patients with ESRD than in control subjects at baseline and after E(2) ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E(2). Therefore, conventional E(2) doses used in individuals with normal renal function may be excessive for patients with ESRD.