Vaginal administration of low-dose conjugated estrogens: Systemic absorption and effects on the endometrium

Objective: To test the hypothesis that a very-low-dose regimen of vaginal estrogen would provide effective relief from atrophic vaginitis without endometrial proliferation. Methods: Twenty postmenopausal women with symptoms, signs, and cytologic evidence of atrophic vaginitis were enrolled. Each subject was treated with 0.3 mg of conjugated estrogens, administered vaginally 3 nights per week for 6 months. We examined the following outcomes: symptoms, vaginal cellular (cytologic) maturity, endometrial histology, sonographic evaluation of endometrial thickness, Doppler measures of uterine artery blood flow, and serum levels of estrone and estradiol. Pre- and post treatment data were compared for each subject. Results: Satisfactory relief of symptoms occurred in 19 of 20 cases. Vaginal cellular maturation improved significantly with therapy (P <.01). There were no significant changes in endometrial thickness, uterine artery blood flow, or serum estrogen levels. Endometrial proliferation was observed in one case. Conclusions: Relief from atrophic vaginitis can be achieved with 0.3 mg of conjugated estrogens administered vaginally three times per week. Endometrial proliferation may occur at this low dose, albeit rarely.