LOW-DOSE ESTRADIOL IN THE TREATMENT OF UROGENITAL ESTROGEN DEFICIENCY - A PHARMACOKINETIC AND PHARMACODYNAMIC STUDY

Twenty-four postmenopausal women with vaginal atrophy due to oestrogen deficiency were treated with 17beta-oestradiol administered as vaginal tablets containing 10 and 25 mug, respectively, in a slow-release system (Vagifem, Novo Nordisk, Denmark). All the women were treated for 2 weeks with each dose in a double-blind, cross-over study. Plasma concentrations of unconjugated oestradiol and unconjugated oestrone were measured at regular intervals for 24 h on days 1 and 14 of each treatment regimen. Cytological and clinical evaluations of the vaginal and urethral epithelium were also carried out. Initially, when the epithelium was still atrophic, dose-dependent absorption of oestradiol was demonstrated. After 14 days of treatment maturation of the vaginal epithelium was seen with both regimens and the absorption of oestradiol then declined significantly on both the 10 and the 25 mug dose. Oestrone levels remained unchanged and gonadotrophin levels were unaffected during treatment. Vaginal cytology showed maturation on both the 10 and the 25 mug dose, whereas urethral cytology showed a reduction in parabasal cells that was significant only on 25 mug. Clinical and subjective improvement was apparent on both doses and acceptance of treatment was good.