EVALUATION OF AN ESTRADIOL CHEMICAL DELIVERY SYSTEM (CDS) DESIGNED TO PROVIDE ENHANCED AND SUSTAINED HORMONE LEVELS IN THE BRAIN

While estrogens readily penetrate the blood-brain barrier and exert significant CNS effects, they are not retained by this organ, obligating constant dosing to achieve sustained and pharmacologically relevant brain concentrations. Such a regimen also generates high peripheral levels of the estrogens which have been linked to metabolic disturbance and cancer. Brain-selective targeting would act to increase the safety of administered drugs by sparing non-target-site tissues. A dihydronicotinate-nicotinate redox targetor designed along these lines was found to be successful in maintaining high central levels of estradiol while peripheral levels were rapidly eliminated. In human clinical trials, the estradiol-chemical delivery system (E(2)-CDS) reduced circulating LH levels to a greater extent than did administered estradiol but caused less of an increase in circulating estradiol blood levels.