Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone.
BACKGROUND
There is a lack of consensus about the safety of estrogen replacement therapy, especially with regard to its impact on a woman's risk for breast cancer. Elevated urinary or serum estrone and estradiol concentrations in postmenopausal women are associated with a moderately elevated risk of breast cancer.


METHODS
Twenty-four-hour urinary steroid hormone profiles, including the measurement of estrone, estradiol, and estriol, were conducted for 35 postmenopausal women receiving oral estradiol at doses from 0.025-2.0 mg/day.


RESULTS
Urinary excretion of estradiol exceeded premenopausal reference range values in women taking estradiol at doses greater than 0.5 mg/day. Urinary estrone excretion exceeded premenopausal reference range values in women taking estradiol doses of 0.25 mg/day or higher. Literature data indicate serum estrone concentrations also markedly exceed premenopausal reference ranges when estradiol is administered orally at a dose of 1 mg/day.


CONCLUSIONS
The previously recommended oral dose of estradiol (1-2 mg/day) results in urinary excretion of estrone at values 5-10 times the upper limit of the reference range for premenopausal women. Retrospective studies associating oral estradiol with increased risk of breast cancer may reflect overdose conditions. Based on current knowledge, a prudent dose ceiling for oral estradiol replacement therapy of 0.25 mg/day is proposed.
Friel
Patrick N
PN
Steroids Department, Meridian Valley Laboratory, 801 SW 16th, Suite 126, Renton, WA 98055, USA. steroids@meridianvalleylab.com
Hinchcliffe
Christa
C
Wright
Jonathan V
JV
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004958:Estradiol / Q000008:administration & dosage / Q000652:urine*; D004964:Estriol / Q000652:urine*; D004970:Estrone / Q000097:blood / Q000652:urine*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis
D004970:Estrone; D004958:Estradiol; D004964:Estriol