Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women

Climacteric. 2016 Apr;19(2):172-80. doi: 10.3109/13697137.2015.1098609. Epub 2015 Nov 19.


Objectives: To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 μg/g (T1) and 50 μg/g (T2)) compared to Ovestinon® (estriol 500 μg/0.5 g (R)) and placebo in postmenopausal women.

Methods: Forty-three volunteers were randomly assigned to received T1, T2, R or placebo once daily for 21 days. Absorption of estriol after single and multiple administration was analyzed. Cytological changes in the vagina, tolerability and safety were also investigated.

Results: Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.65 ± 80.18 (T1) and 406.75 ± 199.53 (T2) pg/ml × h) than with Ovestinon® (1221.97 ± 549.06 pg/ml × h). Estriol exposure of the test formulations after multiple administration (AUCss: 36.33 ± 30.52 (T1) and 73.71 ± 46.86 (T2) pg/ml × h) was significantly lower than after single-dose administration and not significantly different between them. In contrast, the exposure after repeated administration of Ovestinon® was considerable and not statistically different from levels after single administration. All estriol formulations produced similar improvement in the vaginal maturation value, while placebo showed a small and not significant change. Overall safety and acceptability were good.

Conclusions: Estriol 20 and 50 μg/g formulations, while showing a comparable capacity for reversing vaginal atrophy, present a highly favorable safety profile, producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon®.

Keywords: Ovestinon; Vaginal atrophy; estriol; hormone replacement therapy; maturation value; pharmacokinetics; topical.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Aged
  • Atrophy
  • Biological Availability
  • Estriol / administration & dosage*
  • Estriol / adverse effects
  • Estriol / pharmacokinetics*
  • Female
  • Gels*
  • Humans
  • Middle Aged
  • Placebos
  • Postmenopause*
  • Vagina / pathology
  • Vaginal Creams, Foams, and Jellies / therapeutic use
  • Vaginal Diseases / drug therapy


  • Gels
  • Placebos
  • Vaginal Creams, Foams, and Jellies
  • Estriol