Formation of ethinylestradiol in postmenopausal women during continuous treatment with a combination of estradiol, estriol and norethisterone acetate.

Previous studies indicated that during treatment of postmenopausal women with preparations containing norethisterone, a small proportion of the progestogen is aromatized into ethinylestradiol. We therefore investigated the serum concentrations of estradiol, ethinylestradiol and norethisterone in 25 patients of a gynecological practice who were continuously treated for climacteric complaints with a combination of 2 mg estradiol, 1 mg estriol and 1 mg norethisterone acetate for a time period between 4 months and 6 years. Blood sampling occurred between 1 and 20 h after intake of the last tablet. The mean serum concentration of estradiol was 138 +/- 50 (53-279) pg/ml, of ethinylestradiol 18.1 +/- 13.5 (0-44) pg/ml, and of norethisterone 5.1 +/- 3.5 (0.7-11.6) ng/ml. The serum concentrations of estradiol showed a broad maximum between 1 and 14 h, and those of norethisterone a steep rise to maximum within 1-4 h after intake followed by a subsequent decline. Contrary to this, the ethinylestradiol levels were not related to the time after application indicating that the aromatization of norethisterone mainly occurs in peripheral tissue. There was no correlation between age, body mass index or duration of treatment and the ethinylestradiol levels. It is concluded that in the presence of the high estradiol concentrations the low conversion rate of norethisterone into ethinylestradiol is probably without clinical significance.