Background: Endogenous estradiol levels fall significantly after menopause, leading estrogen-dependent tissues to gradually atrophy. Vaginal atrophy can cause dryness, soreness, irritation, and dyspareunia, and may contribute to vaginal and bladder infections. Estrogen therapy can reduce these symptoms. Locally administered estrogen is recommended over systemic estrogen therapy for treating vaginal atrophy, and may be continued for as long as symptoms are bothersome. The typical dose is 25 mcg of estradiol (Vagifem, Estrogel), administered via vaginal tablet or vaginal gel, initially daily and then twice weekly for maintenance. Reports from other studies have indicated that lower doses of estrogen may be as effective for treating vaginal atrophy. Simon and associates studied the effectiveness and safety of a 10-mcg vaginal tablet for treating vaginal atrophy.

The Study: Conducted at 49 sites in the United States and Canada, this double-blind, randomized, placebo-controlled trial enrolled postmenopausal women to receive the 10-mcg dose or placebo. Participants were eligible if they were at least 45 years of age, were at least two years from their last menstrual cycle or from bilateral oophorectomy, and reported at least three urogenital symptoms, including vaginal dryness, itching, irritation, or soreness; dysuria; or dyspareunia and vaginal bleeding with sexual activity. Patients were excluded if they had a history of hormone-dependent cancers or thrombophlebitis, vaginal infections requiring treatment, or any chronic or serious disease that could interfere with study compliance. At baseline, participants underwent transvaginal ultrasonography for measurement of endometrial thickness, endometrial biopsy, and vaginal pH and cytology testing. Each patient was instructed to insert the vaginal tablet at the same time each day for 14 days and then twice a week. Symptoms were assessed at two, four, eight, 12, 26, 39, and 52 weeks, with objective measures including vaginal pH and the percentage of premenopausal- to postmenopausal-type vaginal epithelium.

Results: Of the 309 women enrolled, 104 were randomized to the placebo group and 205 to the treatment group. The two groups were similar in age, years since menopause, and race. There was a significant dropout rate; 33 percent in the placebo group and 20 percent in the treatment group. Using intention-to-treat analysis, it was determined that, starting at two weeks, vaginal health was statistically improved over placebo, and these improvements continued over the 52-week study. Urogenital complaints also trended toward improvement at two weeks and became statistically significant at 12 weeks. Side effects were mild and occurred at similar rates in both groups. Previously published comparisons report low systemic absorption with all vaginal estrogen preparations and no significant differences among them in the incidence of hyperplasia, endometrial thickness, and adverse events.

Conclusion: The study results indicate that 10-mcg estradiol vaginal tablets appear to be effective for treating postmenopausal vaginal atrophy.