Best choice of local therapy is unclear for vulvovaginal symptoms in postmenopausal women
EBM Focus - Volume 13, Issue 15
- Vaginal estrogen therapy may be considered in women with symptomatic vaginal atrophy.
- In a recent randomized trial, 302 postmenopausal women with moderate-to-severe vulvovaginal symptoms were randomized to estradiol 10 mcg vaginal tablet plus inert gel (hydroxyethylcellulose as placebo), vaginal moisturizer plus placebo vaginal tablet, or dual placebo.
- There was no significant difference between the vaginal estradiol tablet and dual placebo groups in rates of clinically important improvement (as defined by the authors) in the most bothersome symptom for each patient. However, more women in the vaginal estradiol group reported a “meaningful benefit from treatment” than in the placebo group (80% vs. 65% with placebo, p = 0.02, NNT 7).
Estrogen therapy (local or systemic) is recommended for women with symptomatic moderate-to-severe vaginal atrophy or for women with symptomatic mild atrophy who do not respond to lubricants and moisturizers (Menopause 2013, Obstet Gynecol 2014). Two previous randomized trials suggest that 10 mcg vaginal estradiol tablets may improve vulvovaginal symptoms in postmenopausal women (Obstet Gynecol 2008a, Obstet Gynecol 2008b). In a recent trial, 302 postmenopausal women (mean age 61 years) with ≥ 1 moderate-to-severe vulvovaginal symptom at least once weekly or dyspareunia at least once monthly were randomized to estradiol 10 mcg vaginal tablet plus inert gel (hydroxyethylcellulose as placebo), vaginal moisturizer (Replens) plus placebo vaginal tablet, or dual placebo. The women were instructed to use the tablets daily for 2 weeks and then twice weekly, and moisturizer/gel on every third day for 12 weeks. The primary outcome was decrease in severity at 12 weeks of most bothersome symptom identified at baseline. Symptom severity was assessed using a 0-3 point scale with 0 indicating no symptom.
At baseline, the most frequent bothersome symptoms were dyspareunia (in 60% of women) and dryness (in 21%), and mean severity of the most bothersome symptom was 2.5 points. There were no significant differences between the vaginal estradiol tablet and dual placebo groups in rates of achieving ≥ 2-point improvement (considered by the authors to be clinically important) on the symptom severity scale of the most bothersome symptom (49% vs. 45% with placebo) or in mean treatment satisfaction assessed with a 10-point Likert scale. However, more women in the vaginal estradiol group reported affirmatively that they had a “meaningful benefit from treatment” than in the dual placebo group (80% vs. 65% with placebo, p = 0.02, NNT 7). There were no significant differences in any of these outcomes comparing the vaginal moisturizer and dual placebo groups. Statistical comparisons between vaginal estradiol and vaginal moisturizer were not reported.
A clearly superior treatment is difficult to identify in this trial due to inconsistent findings depending on how efficacy was defined. The 10 mcg vaginal estradiol tablet was no more likely than hydroxycellulose gel to provide a clinically important improvement (as defined by the authors) in symptom severity assessed with a quantitative scale but was more likely to be described as providing “meaningful benefit from treatment”. This inconsistency raises questions regarding the tools used to measure efficacy. Restricting “clinically important” to a ≥ 2 point reduction on a 4-point scale may be too insensitive to detect an important reduction according to the patient; this assertion is highlighted by the fact that women in the estradiol group were more likely to report a “meaningful benefit” from treatment. In addition, the high rate of women reporting a “meaningful benefit” from treatment with hydroxyethylcellulose gel suggests that simple lubricants may be a reasonable first line therapy. In summary, choice of local treatment for vulvovaginal symptoms in postmenopausal women should be based on patient preference and continued dialog to ensure that therapy can be adjusted to meet patient needs.