Intravaginal dehydroepiandrosterone for the treatment of vulvovaginal atrophy: a systematic review and meta-analysis

IMPORTANCE: Vulvovaginal atrophy (VVA) is a common manifestation of the genitourinary syndrome of menopause, associated with vaginal dryness, dyspareunia, and reduced quality of life. Despite available therapies, effective, safe, and well-tolerated alternatives remain of interest for symptomatic postmenopausal women. OBJECTIVE: To assess the therapeutic efficacy of intravaginal dehydroepiandrosterone (DHEA) for vulvovaginal atrophy in postmenopausal women. EVIDENCE REVIEW: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies published up to July 2025. Search terms included "DHEA," "prasterone," "Intrarosa," and "dehydroepiandrosterone." Randomized controlled trials (RCTs) evaluating intravaginal DHEA in postmenopausal women were included. Data extraction followed predefined inclusion and exclusion criteria. Risk of bias was assessed, and pooled analyses were conducted using random-effects models. FINDINGS: Six RCTs representing five unique RCTs (n=1,611) involving postmenopausal women with VVA were included. Compared with placebo, intravaginal DHEA demonstrated significant improvements in two primary outcomes: vaginal dryness with a mean difference of -0.23 (95% CI, -0.35 to -0.11) and dyspareunia of -0.40 (95% CI: -0.66 to -0.15). No major safety concerns were reported, and adverse effects were mild and infrequent. The evidence consistently supported both statistical and clinical benefits of DHEA across trials, with low to moderate heterogeneity. CONCLUSIONS AND RELEVANCE: Intravaginal DHEA significantly improves vulvovaginal symptoms, particularly vaginal dryness and dyspareunia, in postmenopausal women. These findings underscore its role as an effective and well-tolerated therapeutic option for the management of genitourinary syndrome of menopause, with potential to enhance quality of life.