Review of the endometrial safety during intravaginal treatment with estriol.

To gain more insight into whether intravaginal treatment of local urogenital complaints with the mild-acting oestrogen estriol is capable of inducing proliferation of the endometrium, the results of the clinical studies that have been published over the years have been pooled. Of a total of 19 studies that initially had been selected, four were excluded from the analysis because no baseline biopsies were available, two because endometriae had been evaluated using methods other than with histology, and one study because a sustained-release preparation was used. Pooling of 12 studies (214 subjects) revealed a reasonable amount of long-term data on intravaginal estriol treatment with 61 evaluable biopsies after 6 months and 58 after 12 months. In addition, 13 biopsies were available after 2 years. It appeared that intravaginal estriol treatment using the recommended dosages did not result in endometrial proliferation. All 337 post-baseline biopsies that have been reported in the literature were classified as atrophic. It can be concluded that single daily treatment with intravaginal estriol in the recommended doses in postmenopausal women is safe and without an increased risk of endometrial proliferation or hyperplasia. Consequently, there is no need to add sequential progestogens with these preparations and no withdrawal bleedings will be induced.