New evidence for the selective, long-lasting central effects of the brain-targeted estradiol, Estredox

The present study examined the dose- and time-dependent central effects of an estradiol chemical delivery system cyclodextrin complex (E 2-CDS–CD) on the reestablishment of copulatory behavior of castrated male and ovariectomized female rats with concomitant determination of the blood luteinizing hormone (LH) and E 2 levels. In orchidectomized males, Estredox, after single doses of 0.3 and 3.0 mg/kg iv, reestablished the mounting and intromission up to 4 weeks. The LH suppressive effect lasted to Day 7 and 28, respectively. After repeated administration for 10 days at a dose of 0.01mg/kg iv, significant effect was obtained by Day 14. Ovariectomized females were treated iv daily for 5 days either with E 2-CDS–CD, estradiol benzoate (EB) or vehicle, and the lordosis quotient was determined. At a dose of 0.03 mg/kg the duration of EB's effect was 10 days shorter and only one-third of that of E 2-CDS–CD. The LH suppression lasted to Day 18. On the other hand, after EB treatment there was no significant decrease in LH levels. The low plasma E 2 levels indicated fast rate of peripheral elimination in both males and females. The brain-targeting E 2 indicates better efficacy and increased safety in replacement therapies because of the reduced peripheral side effects.