Randomized, double-blind, dose-ranging study of the endometrial effects of a vaginal progesterone gel in estrogen-treated postmenopausal women.

OBJECTIVE

Our purpose was to assess the endometrial effects of two doses of natural progesterone administered by a bioadhesive vaginal gel in estrogen-treated postmenopausal women.

STUDY

DESIGN

This was a double-blind, randomized, dose-ranging study of 31 postmenopausal women attending a specialist menopause clinic. Endometrial histologic features, sex steroid hormone concentrations, and vaginal bleeding patterns were assessed during three 28-day cycles of continuous oral conjugated estrogens (0.625 mg/day) and two doses of sequential vaginally administered natural progesterone (45 or 90 mg every 48 hours). Histologic results are presented descriptively. Between-group comparisons of other parameters were made with the use of the Mann-Whitney U and Student t tests.

RESULTS

Secretory endometrium was found in 35 of 41 histologic samples that yielded adequate tissue for diagnosis. There was one case of proliferative endometrium in the 45 mg progesterone group and none in the 90 mg group and no cases of hyperplasia. Mean plasma progesterone concentrations of 4.6 ng/ml and 6.8 ng/ml were achieved in the 45 and 90 mg groups, respectively.

CONCLUSIONS

Very low doses of natural progesterone, when administered vaginally in a bioadhesive gel, cause secretory endometrial transformation in estrogen-treated postmenopausal women.