Dominance of estradiol metabolism at the D-ring over the A-ring metabolism may play
a role in the pathophysiology of human breast carcinogenesis. Currently, the influence
of progestins on breast cancer risk is debated when added to postmenopausal estradiol
replacement therapy. However, nothing is known about the action of progestins on estradiol
metabolism. Therefore, the effect of oral and transdermal estradiol/norethisterone
acetate (NETA) was investigated on the ratio of the main D-ring metabolite 16α-hydroxyestrone
(16-OHE1) to the main A-ring metabolite 2-hydroxyestrone (2-OHE1). The ratio of 16-OHE1
to 2-OHE1 after transdermal hormone replacement therapy (HRT) was 0.43 before treatment,
0.35 after estradiol and 0.52 after estradiol + NETA. The ratio after oral HRTwas
0.94 before treatment, 0.86 after estradiol and 2.30 after estradiol+NETA. Because
of the high variations, no statistical significance could be calculated. Since there
was a tendency to an increase after oral estradiol+NETA treatment, the individual
patient profiles were examined. Here, three patients in the oral treatment group showed
a significant increase of the ratio after the estradiol/NETA phase. In conclusion,
transdermal NETA in HRT did not elicit any change in estrogen metabolism after 2 weeks'
treatment. However, oral NETA may in some cases have an impact on estradiol metabolism
which should be further evaluated.
Key words
Estradiol metabolism - Transdermal and Oral Estradiol Replacement Therapy - Norethisterone
Acetate - Postmenopausal Women
