Short-term outcomes using of hyaluronic acid injection for genitourinary syndrome of menopause: a pilot study

Estrogen deficiency associated with menopause leads to genitourinary syndrome of menopause (GSM), for which effective non-hormonal treatment options are particularly needed in breast cancer survivors where hormonal therapies are often contraindicated. This study aimed to evaluate the clinical efficacy, impact on sexual function, and mucosal changes of a standardized intravaginal hyaluronic acid (HA) injection technique as a non-hormonal treatment for GSM symptoms.

This multicenter prospective pilot study included 42 postmenopausal women aged 45-65 years with GSM symptoms and a vaginal health index (VHI) score ≤15. After eligibility assessment, baseline vaginal mucosal punch biopsies were obtained from all participants. Subsequently, 2 mL of multifractional, intercalated HA (Armonia Regenyal) was administered intravaginally using the standardized cannulated intravaginal injection technique. Follow-up vaginal biopsies were collected 1 month after the procedure. Clinical outcomes were assessed using the VHI, visual analog scale (VAS), and female sexual function index (FSFI) before and after treatment. Histopathological evaluation included epithelial thickness, capillary density, glycogenization, and neo-collagenization. Primary outcomes were changes in VHI, VAS, and FSFI scores, while secondary outcomes included histological parameters of vaginal tissue remodeling.

A statistically significant improvement was observed in VHI, VAS, and FSFI scores in all participants following HA injection (P = .0001 for all). Histological analysis demonstrated significant increases in epithelial thickness and capillary density after treatment (P = .0001 for both). Post-intervention biopsies revealed glycogenization in 54.8% of cases, neo-collagenization in 95.2%, and increased prominence of dermal papillae in 57.1% of samples.

Vaginal MIC-HA injection was associated with significant improvements in GSM symptoms and sexual function, accompanied by objective histopathological evidence of improved vaginal tissue quality, including increased epithelial thickness, vascularization, and neo-collagenization. These findings suggest that MIC-HA may provide both symptomatic and tissue-level benefits in women with GSM. However, the relatively small sample size and incomplete follow-up biopsies limit the generalizability of the findings. Larger, controlled studies with longer follow-up are needed to confirm these results.

Standardized intravaginal multifractional intercalated medium cross-linked HA injection appears to be a safe and effective non-hormonal intervention that provides significant clinical and histological improvement in women with GSM.Clinical trial registration number: NCT05559996.