NAMS: Estrogen Cream Eases Vaginitis with No Endometrial Safety Signals

By Charles Bankhead
ORLANDO, 29 septc 2008-- Moderate to severe atrophic vaginitis can be eased for postmenopausal women by either of two low doses of estrogen cream, with no endometrial safety signals, investigators reported here.
Both low-dose regimens of the conjugated estrogen cream led to significant improvement in vaginal maturation index, vaginal pH, and most bothersome symptoms compared with placebo, Gloria Bachmann, M.D., of Robert Wood Johnson Medical School in New Brunswick, N.J., said at the North American Menopause Society meeting.
The improvement was statistically significant at 12 weeks and persisted during follow-up for a year.
In a subgroup of patients who had endometrial biopsies, no cases of endometrial hyperplasia or carcinoma occurred with either estrogen cream regimen.
"Low-dose [vaginal estrogen cream] represents an important therapy for treating atrophic vaginitis without endometrial safety concerns over a one-year study period," Dr. Bachmann and colleagues concluded.
As many as 40% of postmenopausal women are affected by atrophic vaginitis. Vaginal application of topical low-dose estrogens is thought to reduce systemic exposure to estrogen and limit its stimulatory effects on the endometrium, the investigators said.
Both daily and twice-weekly vaginal administration of low-dose vaginal estrogen cream have demonstrated efficacy for reducing symptoms of atrophic vaginitis. Dr. Bachmann reported findings from a randomized clinical trial comparing the two regimens.
The study involved 423 postmenopausal women who were randomized and received at least one dose of assigned therapy. The patients had symptoms of moderate or severe atrophic vaginitis, including a baseline composite symptom score of 5 for vaginal dryness, itching, burning, and dispareunia; a total score of <15 on the General Health Clinical Evaluation.
The patients were randomized to four treatment groups: daily or twice-weekly vaginal estrogen cream (0.5 g) or a matching placebo group for each administration schedule. Patients assigned to daily treatment were on therapy for 21 days, followed by seven days off.
The primary efficacy assessment was the change from baseline to week 12 in vaginal maturation index, vaginal pH, and most bothersome self-reported symptom. Patients continued open-label treatment of assigned therapy for the remaining 40 weeks.
Both active-therapy regimens led to significantly greater improvement in all outcome measures at 12 weeks compared with placebo.
A total of 155 patients treated with either regimen of vaginal estrogen cream had evaluable endometrial biopsies. In the patients assigned to daily therapy, six of 85 had evidence of proliferative endometrium. Among 72 assigned to twice-weekly treatment, six had proliferative endometrium.
No patient in either group developed endometrial hyperplasia or carcinoma. Transvaginal ultrasound at the end of the study revealed endometrial thickness ≥5 mm in 18 patients assigned to daily vaginal estrogen cream and in 12 patients on the twice-weekly regimen.
In general, adverse events were similar in the active-treatment and placebo groups, Dr. Bachmann reported, and treatment-emergent adverse events were uncommon. Treatment-emergent vaginal bleeding occurred in no more than two patients in any randomized group during the double-blind and open-label phases of the study.
The study was supported by Wyeth Research.
Investigators in the study included Wyeth employees.
Primary source: North American Menopause Society meetingSource reference:Bachmann G, et al "Endometrial safety of two low-dose regimens of conjugated estrogens vaginal cream in postmenopausal women with atrophic vaginitis over one year of therapy" NAMS Meeting 2008.