Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms

Abstract

IMPORTANCE Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments. OBJECTIVE To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms. DESIGN, SETTING, AND PARTICIPANTS This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration. INTERVENTIONS Vaginal 10-μg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100). MAIN OUTCOMES AND MEASURES The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score-Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH. RESULTS The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, −1.4 (95% CI, −1.6 to −1.2); moisturizer, −1.2 (95% CI, −1.4 to −1.0); and placebo, −1.3 (95% CI, −1.5 to −1.1). No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) (P = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P = .17). CONCLUSIONS AND RELEVANCE Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02516202

TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women

“…dyspareunia) as required by the FDA, but rather evaluated many different symptoms as a single entity. Nonetheless, the MsFLASH trial found significantly greater improvement in total Menopause-specific Quality of Life Questionnaire scores with the vaginal E2 tablets compared with the placebo gel 16 , and objective findings (vaginal pH and vaginal maturation index) as well as patient satisfaction favored the vaginal E2 tablets versus the placebo gel 14 . Therefore, these results are limited in scope, and clinicians should not disregard the large body of evidence showing that low-dose vaginal estrogen can be useful in the management of GSM.…”

“…While data from the 12-week GSM trial from the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) research group suggest that prescribing vaginal 10-mg E2 tablets and over-the-counter vaginal moisturizer does not provide additional benefit over a placebo vaginal tablet and gel in reducing postmenopausal VVA symptoms 14 , the trial had several limitations. As noted by Pinkerton et al 15 , the trial had a small sample size (n ¼ 302); used a non-conventional placebo gel, which might have contributed to the high placebo response; and did not evaluate a specific MBS (i.e.…”

<p>Ospemifene in the Management of Vulvar and Vaginal Atrophy: Focus on the Assessment of Patient Acceptability and Ease of Use</p>

“…Specifically, the beneficial effects of vaginal moisturizers are mostly due to adhesive and buffering capacities leading to tissue water retention and vaginal pH reduction. 21 Polycarbophil based moisturizers are as effective as vaginal oestrogen therapy in reducing postmenopausal VVA symptoms 22,23 but not in improving sexual function and menopause-related quality of life. 24 Low dose local oestrogens, in the form of cream, tablet, or ring are all effective for VVA symptoms, with a minimal systemic absorption.…”

Effectiveness of hormones in postmenopausal pelvic floor dysfunction—International Urogynecological Association research and development—committee opinion

“…A systematic review, published in 2014, concluded that all commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, stress urinary incontinence (SUI) and UUI, and recurrent UTIs [2]. However, a recent large RCT concluded that neither the vaginal estradiol tablet nor the over-the-counter vaginal moisturizer provided additional benefit over placebo in reducing postmenopausal VVS [21].…”