Serum concentrations of estriol vary widely after application of vaginal estriol cream.

AIM To establish the pharmacokinetic profile of serum estriol (E3 ) concentrations over 24-hours following application of vaginal E3 in chronic users (>12 weeks of E3 use). The interindividual and intraindividual differences before and after E3 were examined. METHODS Ten women participated. Vaginal cream was omitted for >36 hours prior to the study days. Blood sampling was performed for E3, estradiol and estrone concentrations prior to cream application and at 1, 2, 3, 5, 8, 10, 12 and 24 hours afterwards. In five women, all samples were repeated on a separate day. RESULTS E3 was absorbed rapidly in most women. Peak serum E3 concentration occurred around 2 hours (range 1-5 hours). The decline in E3 concentrations was also rapid: falling <100 pmol L-1 in 6/10 women within eight hours and returning to ≤ 10 pmol L-1 at 24 hours in 9/10 patients. Interindividual variability for peak concentrations was considerable (mean 546 pmol L-1 ; 95% CI 349 - 743). Area under Concentration Time Curve (AUC) values over a dosage interval also varied widely: mean 2145 pmol.h L-1 ; 95% CI 1422 - 3233. However, repeated measurements in the same woman were highly (peaks: ρ= 0.94) or moderately (AUC: p= 0.74) correlated. CONCLUSIONS Post-menopausal E3 concentrations are negligible. Serum E3 concentrations of chronic users of E3 cream varied greatly, however concentrations declined rapidly within eight hours, generally reaching "post-menopausal" levels by 24 hours. The basis for the variation between subjects needs further elucidation. Additional research is required to establish the safety of topical E3 .