Clinical trial of the estradiol vaginal ring in the U.S

Vaginal atrophy can be reversed for most women through systemic hormones. Those women who cannot take systemic hormones can get relief of symptoms with local estrogen therapy, which ideally should be locally effective without significant systemic absorption and without endometrial stimulation. An estradiol-releasing vaginal ring was therefore tested for efficacy, safety and patient acceptability in a 15-week open-label, randomized parallel group trial with blinded evaluations of the cytological response data. Conjugated estrogen vaginal cream was used as a reference control. The primary objectives of the study were to evaluate whether the two treatments were equivalent regarding improvement in urogenital atrophy, improvement in physicians's overall evaluation of product performance on urinary and/or vaginal changes, and improvement in patient's assessment of urinary and/or vaginal symptoms. A secondary objective was to assess frequency of endometrial overstimulation during estrogen replacement therapy, to be measured by a progestogen challenge test. The ring and cream treatment produced an equivalent effect on the vaginal mucosa, and equivalence was also found in physician's and patient's assessments of both vaginal and urinary symptomatology. Both treatments were equally effective in improving the vaginal pH toward levels normally seen in fertile women (< 5.0). With regard to endometrial stimulation, significantly more patients had bleedings at progestogen challenge test after 3 months of treatment with cream than with the ring. The ring, however, was given significantly better overall product acceptability ratings by the patients. It can therefore be seen as an equally effective, but significantly more acceptable, new administration form for treatment of urogenital disorders due to estrogen deficiency, with a more favourable safety profile than vaginal cream.