Sustained-release subdermal estradiol implants: A new alternative in estrogen replacement therapy

Abstract

This trial was a therapeutic and pharmacokinetic dose-finding study with subdermal implants that showed a constant in vitro daily release rate of estradiol. The aim was to find the daily release rate of estradiol that produces serum estradiol concentrations comparable with those obtained with transdermal estradiol at 0.05 mg/day. The study was an open crossover comparison of transdermal and subcutaneous delivery systems. Thirty-six postmenopausal (serum follicle-stimulating hormone concentration > 30 IU/L before commencing the study) were treated with transdermal estradiol for 4 weeks. Immediately after this transdermal estradiol delivery was replaced by either one or three estradiol implants. The serum concentrations of estrone, estradiol, follicle-stimulating hormone, and sex hormone-binding globulin were followed up for 8 weeks on implant therapy and compared with those during transdermal estrogen administration. To oppose the estrogen effect on the endometrium, each patient received an intrauterine device releasing a progestin, levonorgestrel. The serum estradiol concentrations achieved with three implants were comparable with those during transdermal administration of estradiol at 0.05 mg/day. Suppression of follicle-stimulating hormone was also better maintained with three implants compared with one. This study shows that constant release profiles can be achieved with nonbiodegradable estradiol implants. The results suggest that a single application should give sufficient estrogen substitution for more than a year.