Oral full-spectrum sodium hyaluronate for vulvovaginal atrophy in postmenopausal women: a randomized, parallel-group clinical trial

Vulvovaginal atrophy (VVA), a major component of the genitourinary syndrome of menopause (GSM), is highly prevalent and often undertreated. Given the chronic nature of symptoms, safe and effective non-hormonal strategies suitable for long-term use are needed. Hyaluronic acid (HA) is effective when administered locally and emerging evidence suggests potential benefits of oral full-spectrum HA formulations. To explore the efficacy and tolerability of an oral full-spectrum sodium hyaluronate formulation (ExceptionHYAL ® Blossom) in postmenopausal women with VVA, and to assess its potential adjuvant effect when combined with a vaginal HA ovule. In this 60-day exploratory open-label randomized clinical trial, 60 postmenopausal women with VVA were allocated (1:1:1) to oral sodium hyaluronate, vaginal HA ovule, or combined oral plus vaginal treatment. Assessments at baseline, day 30, and day 60 included the Vaginal Health Index (VHI), Visual Analog Scales (VAS) for symptom severity, Vulvovaginal Symptom Questionnaire (VSQ), gynaecological examination, and global patient evaluations. VHI scores increased significantly in all groups at day 30 and day 60. At day 60, the combination group showed significantly higher VHI values than both monotherapy groups, and oral treatment alone was superior to vaginal treatment alone. All VVA-related symptoms significantly decreased across all groups, with greater improvements in the oral and combination groups. Oral full-spectrum sodium hyaluronate significantly improves objective vaginal health and patient-reported symptoms in postmenopausal women with VVA. The greatest benefit was observed when oral supplementation was combined with vaginal HA, supporting its role as an effective non-hormonal strategy for GSM management.