Effect of norethisterone acetate on estrogen metabolism in postmenopausal women

Dominance of estradiol metabolism at the D-ring over the A-ring metabolism may play a role in the pathophysiology of human breast carcinogenesis. Curr ently, the influence of progestins on breast cancer risk is debated when ad ded to postmenopausal estradiol replacement therapy. However, nothing is kn own 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 16 alpha -hydroxyes trone (16-OHE1) to the ma in A-ring metabolite 2-hydroxyestrone (2-OHE1). T he 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 estra diol + NETA. The ratio after oral HRT was 0.94 before treatment, 0.86 after estradiol and 2.30 after estradiol+NETA. Because of the high variations, n o 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 sh owed 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 Z weeks' treatment. However, oral NETA may in some cases h ave an impact on estradiol metabolism which should be further evaluated.