Comparison of the Efficacy of Vaginal Hyaluronic Acid to Estrogen for the Treatment of Vaginal Atrophy in Postmenopausal Women: A Systematic Review

Topical estrogen is effective for treating postmenopausal vaginal atrophy. However, there is a potential risk of estrogen-related adverse effects. There is a need for finding effective non- hormonal treatment for vaginal atrophy. The topical application of moisturising agents, such as hyaluronic acid (HA), represents a promising non-hormonal treatment for the relief of vaginal atrophy. This study aimed to summarize the evidence regarding the efficacy of topical HA compared to topical estrogen in postmenopausal women with vaginal atrophy. The literature search covered English-published studies from database inception till February 2023. The search included the electronic databases of MEDLINE/PubMed, Cochrane Library, Web of Science, ProQuest, and Scopus, using the terms "Hyaluronic Acid" AND "Postmenopause" AND "Vagina" AND "Atrophy". Due to the diversity in reporting outcomes, meta-analysis was not feasible. A narrative synthesis with a systematic approach was conducted by vote counting of studies that included a direct comparison between topical HA and topical estrogen. Six studies were included. Intra-group comparisons showed that both interventions were significantly effective in alleviating the symptoms of vaginal atrophy and dyspareunia as well as improving vaginal pH and cell maturation index. However, inter-group comparisons in most studies showed that estrogen was superior to HA in relieving vaginal symptoms and improving vaginal pH, dyspareunia, and the cell maturation index. There is no evidence to show the superiority of HA to estrogen in the treatment of postmenopausal vaginal atrophy. However, the therapeutic efficacy of HA seems to be comparable to estrogen and considering its safety, HA can be used as an alternative to estrogen in patients who do not want to use estrogen. The available studies have several limitations, and the reporting of outcomes was considerably heterogeneous.