Serum concentrations of 17β-estradiol in ovariectomized rats during two times six weeks crossover treatment by daily injections in comparison with slow-release pellets

Estrogens exert widespread biological functions that reach far beyond their well-known role in reproduction. Exogenous administration of 17 beta-estradiol to ovariectomized experimental animals is of the utmost importance in elucidating its mechanisms of action. In the present study, we compared two different modes of exogenous administration of 17 beta-estradiol to ovariectomized rats in relation to the serum 17 beta-estradiol concentrations over prolonged periods of time. 17 beta-estradiol was administered either by slow-release pellets (Innovative Research of America, Sarasota, Fl. 34236, USA, 90-day release, NHH-115, 1.5 mg) or by daily subcutaneous injections of 15 mg 17 beta-estradiol dissolved in sesame oil. After 6 weeks, the mode of administration of estradiol was changed to the opposite method and continued for a further 6 weeks. Blood samples for measurement of serum 17 beta-estradiol were taken every second week. After 2 weeks, the serum concentrations of 17 beta-estradiol in group A initially receiving the pellets were 73% higher (p < 0.001) compared to those of group B receiving daily injections. The difference was even more prominent, 580% (p < 0.001), after 4 weeks. Steady state was reached at week 6 in group A, but already by week 4 in group B. Once steady state was reached, the concentrations were the same in both groups for the remainder of the experiment (12 weeks in total). Our study indicates that steady-state concentrations of 17 beta-estradiol occur 5-6 weeks later than the 48 h the manufacturer of the slow-release pellets claims.