'Pulsed' estradiol action can stimulate breast cancer cell proliferation.
OBJECTIVE
The newly available nasal estradiol application serum concentrations measure up to 10-fold higher compared to common hormone replacement therapy (HRT). Since this has only a short-time peak it has been suggested that breast cancer risk may be reduced, because of lower activation of the estradiol-receptor-transcription cascade.


METHODS
Estradiol was tested at 10(-9) and 10(-8) M corresponding to the serum levels achieved with nasal application. In addition also comparable exposure times were investigated: Incubation time was 10, 20, 40, 60 and 180 min every day for four days, compared with continuous non-stop incubation for four days. The well-recognized MCF-7 breast cancer cell line was used. Cell proliferation was measured by the ATP-assay.


RESULTS
Estradiol in concentrations achieved with 'pulsed' HT was able to elicit proliferation of MCF-7 cells already after an incubation time of ten minutes which correlates with the minimum of exposure time using nasal estradiol application. Compared to non-stop continuous estradiol added in the same high concentrations over four days no significant differences were observed.


CONCLUSIONS
Short-time application of estradiol is able to stimulate breast cell proliferation to the same degree as continuously administered estradiol in high concentrations. Thus it remains questionable, if a 'pulsed' estradiol therapy may reduce breast cancer risk during HRT. Clinical studies are urgently needed to reveal the breast cancer risk during nasal estradiol application especially since this risk might be increased depending on the concentrations used.
Mueck
A O
AO
Section of Endocrinology and Menopause, University Women's Hospital, Tuebingen, Germany.
Seeger
H
H
Wallwiener
D
D
D000281:Administration, Intranasal; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D014407:Tumor Cells, Cultured
D004958:Estradiol