Plasma concentrations of medroxyprogesterone acetate, estradiol and estrone following oral administration of klimaxil®, trisequence® / provera® and divina®. A randomized, single-blind, triple cross-over bioavailability study in menopausal women

Abstract The absorption of estradiol and medroxyprogesterone acetate was investigated in a randomized single-blind, triple cross-over study, in 12 menopausal women, for four different HRT drugs (Klimaxil®, a combination tablet containing 17β-estradiol 2 mg and medroxyprogesterone acetate 5 mg; Divina®, a combination tablet containing 17β-estradiol valerate 2 mg and medroxyprogesterone acetate 10 mg; Trisequence®, a triphasic preparation containing 17β-estradiol 2 mg in the first phase; Provera®, a tablet containing medroxyprogesterone acetate 5 mg). Trisequence and Provera were ingested simultaneously. In conclusion, there was no statistically significant difference between the drugs with respect to the estradiol levels. The estrone concentration, however, differed between the different drugs. The serum concentration was higher after intake of tablets containing estradiol than after intake of tablets containing the valerate ester. There was a significant increase in the MPA levels between periods 1 and 3. Finally, Divina produced higher MPA concentrations than Klimaxil and the combination of Trisequence and Provera, although the mean AUC was not twice as high, as might have been expected.