Assessment of the Efficacy of Injectable Hyaluronic Acid for Genitourinary Syndrome of Menopause

Assessment of the Efficacy of Multifractional Intercalated Hyaluronic Acid Injection for Genitourinary Syndrome of Menopause

The vaginal wall consists of epithelium, lamina propria, muscularis and adventitia (1). The decrease in postmenopausal estrogen levels causes thinning of the vaginal wall thickness and the development of genitourinary menopause syndrome (GSM), which is characterized by vaginal dryness, burning, pruritus, urinary complaints and sexual discomfort (2).

In the treatment of GSM symptomatology, there are many different non-hormonal treatment options such as vaginal topical agents and energy-based devices, as well as estrogen-based hormonal therapies (3). The main problem with non-hormonal treatments is the short-term resolution of vaginal atrophy and the lack of long-term results, while contraindications such as breast cancer history and unwillingness of the women to use hormones are problematic for estrogen-based treatments.

Considering all these issues, there is a search for new therapeutic agents with long and high efficiency and safety profile in the treatment of GSM. Hyaluronic acid (HA) which is one of the main components of the extracellular matrix and has water-binding property that provides moisturizing and lubricating effect (4). Besides, it is also reported as the key to the process of tissue regeneration through inflammation, cellular migration and angiogenesis (5). For these reasons, it seems to be a promising treatment of GSM symptomatology.

HA has many routes of administration, such as vaginal gels, ovules, and suppositories, and studies have shown that locally applied HA preparations have a short-term therapeutic effect on GSM symptoms (6). However, there is no consensus regarding HA efficacy due to heterogeneity of studies. Since it is an endogenous molecule, it can be thought that it will be more effective if it is injected directly into the epithelium rather than locally applied.

The injectable form of multifractional intercalated cross-linked HA (MIC-HA) (Armonia®, Regenyal, Italy) is designed for the reinforcement of the extracellular matrix in the female genital area. We intend to investigate and objectively evaluate the efficacy of MIC-HA injection on GSM symptoms and sexual functions in postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Genitourinary Syndrome of Menopause
• Intervention / Treatment: Device: Injectable form of multifractional intercalated cross-linked hyaluronic acid (Armonia®, Regenyal, Italy)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey
  • İstanbul, Turkey, 34844
    • Maltepe University Faculty of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Vaginal dryness Burning Itching Dyspareunia Genital discomfort

-

Exclusion Criteria:

Presence of pelvic organ prolapse Vaginal infections History of genital carcinoma Vulvovaginal dystrophic diseases Previous vaginal surgery Current use of vaginal moisturizer or lubricant, and use of estrogen History of allergies to hyaluronic acid, betadine or lidocaine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyaluronic acid injection	Device: Injectable form of multifractional intercalated cross-linked hyaluronic acid (Armonia®, Regenyal, Italy); 2 mL of Armonia was injected into the vaginal wall with a standardized injection technique called Cannulated Intravaginal Injection Technique®. In this technique, Armonia® was injected as drops at 40 different points on the entire vaginal wall using 8 different entry points

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
vaginal punch biopsy	4-6 millimeter depth vaginal punch biopsy was taken from the posterior wall of vagina, between 6 and 7 o'clock, 1 cm inside from the hymen by a true-cut punch biopsy device (Robbins® True-Cut Disposable Biopsy Punch 5mm, Robbins Instruments, 2003 Edwards St. Houston, TX 77007). Histologically, epithelial thickness, vascularity and dermal papilla prominence were evaluated. Periodic acid schiff (PAS) staining was used to evaluate glycogenization in epithelial cells, while Masson's trichrome histochemical staining was used to evaluate the distribution and density of collagen (neo-collagenization) in the lamina propria	One month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Turkish validated form of the Female Sexual Function Index	2 (minimum)-36 (maximum). Higher scores mean better outcome	One month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale	0 (minimum)-10 (maximum). Higher scores mean worse outcome	One month
Vaginal health index score	5 (minimum)-25 (maximum). Higher scores mean better outcome	One month

Collaborators and Investigators

• Sponsor: Maltepe University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: menopause; sexual dysfunction; hyaluronic acid; vulvovaginal atrophy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: 2020/900/88

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No