Estriol modifies the absorption of estrone and estradiol in castrated rhesus monkeys: a new therapeutic approach for the use of natural estrogens in the menopause?

In order to study the effects of estriol (E3) on estradiol (E2) and estrone (E1) absorption in the rhesus monkey the following study was performed. Chronically ovariectomized animals were divided in four groups of five each according to the treatment protocol (1) E1: 0.7 mg (2) E1: 0.7 mg + E3: 0.135 mg (3) E2: 0.3 mg, (4) E2: 0.3 mg + E3: 0.135 mg (5) E1: 0.7 mg + E2: 0.3 mg and (6) E1: 0.7 mg + E2: 0.3 mg + E3: 0.135 mg. Monkeys received daily drug administration (DA) for 10 consecutive days. Serum E1, E2 and E3 were determined by RIA on a daily basis. In addition, during the first day of treatment blood samples were obtained at hourly intervals. Results were analyzed by comparing the areas under the curve (Integral tests). The data shows that during treatment serum concentrations of E1 and E2 in groups 1, 3 and 5 were significantly higher than in groups 2, 4 and 6 (2-4-fold greater). Serum levels of E1 and E2 rose 5-fold from baseline in animals from group 1 within 1 h, while they increased only 2-fold in those from group 2 at 3-6 h after DA. Similarly, serum levels of E1 and E2 increased 30- and 10-fold respectively 1 h after DA in group 3, while they rose 12- and 5-fold respectively 4 h after DA in animals of group 4. Estriol levels were similar in animals from group 2 and 4 throughout the study (250 +/- 80 pg/ml). It may be concluded therefore that the oral administration of estriol diminishes the absorption of both E1 and E2 and alters their bioavailability, perhaps modulating their biological activity.