Pharmacokinetics of estrogen and progesterone in chronic kidney disease

Abstract

Estradiol, estrone, and estrone sulfate are the primary circulating estrogens in women; the relative amounts depend on the menopausal status of the women. Administration of oral estradiol or conjugated equine estrogens (CEE) results in a high ratio of estrone to estradiol, whereas use of nonoral routes (dermal, vaginal, or parenteral) results in approximately equal plasma concentrations of estradiol and estrone. Although estradiol and estrone are predominately eliminated by metabolism, and little is excreted unchanged in the urine, evidence indicates that chronic kidney disease (CKD) alters the pharmacokinetics of estradiol. Free and total estradiol plasma concentrations are higher in women with end-stage renal disease (ESRD) after an oral estradiol dose, but no change occurs in estrone concentrations. Neither estradiol nor estrone is removed in the dialysate. These studies suggest that women with CKD should receive a least a 50% reduction in oral estradiol doses. No information is available on the pharmacokinetics of any of the progestins in CKD. In the future, knowledge of the concentration effect relationship for the treatment of symptoms of menopause, as well as prevention of osteoporosis, will benefit all postmenopausal women who choose to use hormone replacement therapy.