Vaginal estrogen for genitourinary syndrome of menopause

Local vaginal estrogen therapy is effective treatment for atrophic vaginitis and other symptoms associated with genitourinary syndrome of menopause. However, only about half of the women reporting symptoms seek medical attention. Patients are hesitant to use vaginal estrogens despite evidence of efficacy. This hesitancy demonstrates the need for an updated comprehensive review of the efficacy and safety of both vaginal estrogens and alternatives for treating patients with genitourinary syndrome of menopause to help health care providers and patients choose the most appropriate treatment. The aim of this systematic review was to identify articles in the literature that compare the safety and efficacy of vaginal estrogen products with placebo, each other, systemic estrogen, and nonhormonal vaginal alternatives for the management of genitourinary syndrome of menopause and to generate evidence-based practice guidelines. Data were obtained from MEDLINE and Cochrane Central Register of Controlled Trials from their inception until April 2013. The search included randomized controlled trials and prospective comparative studies conducted in postmenopausal women. All commercially available vaginal estrogen products available for local therapy were allowed as interventions and comparators. Additional comparators included placebo, no intervention, systemic estrogen therapy (all routes), nonhormonal moisturizers, and vaginal lubricants. Nine reviewers double-screened 1805 abstracts, 44 of which met criteria for inclusion. Discrepancies were adjudicated by another reviewer. Fourteen studies (including 4232 participants) were identified that compared vaginal estrogen with placebo (or no treatment). Methodologic quality and strength of evidence of the studies were individually and collectively assessed. Primary outcomes of interest were patient-reported subjective symptoms of genitourinary syndrome of menopause: vaginal dryness, dyspareunia, dysuria, frequency or nocturia, stress urinary incontinence, urge urinary incontinence (UUI), and urinary tract infection (UTI). Objective measures were also assessed and included urodynamic measures, effects on the endometrium, changes in levels of serum estradiol, and adverse events. Both subjective and objectives measures were compared with placebo. Vaginal estrogens improved dryness, dyspareunia, urinary urgency, and frequency. Stress urinary incontinence and UUI were also improved, and the rates of UTI decreased. Different estrogen products at typical doses and frequencies had similar efficacy and safety; levels of serum estradiol were above postmenopausal norms only for high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma occurred rarely in women receiving vaginal estrogen. Comparison of vaginal estrogen with nonhormonal moisturizers showed that patients with 2 or more symptoms of vulvovaginal atrophy were substantially more improved by vaginal estrogens; patients with 1 or minor complaints had similar symptom resolution with either treatment. These data show that all commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints associated with genitourinary syndrome of menopause, substantially improving symptoms of urinary urgency, frequency or nocturia, stress urinary incontinence, and UUI and reducing the frequency of recurrent UTIs. Nonhormonal moisturizers appear to be useful alternatives for patients with few or minor atrophy-related symptoms and those at risk for estrogen-responsive neoplasia.