Efficacy and Safety of CO₂ Laser Therapy Combined With Collagen Cream in Managing Vulvo-Vaginal Atrophy: A Randomized, Controlled Study on Symptom Relief and Microbiome Modulation

This study evaluated a new treatment for postmenopausal women suffering from vulvo-vaginal atrophy (VVA), a condition that causes dryness, burning, and pain. Researchers tested whether combining CO₂ laser therapy with a collagen-based cream could improve symptoms more effectively than laser treatment alone.

Study Overview

• Status: Completed
• Conditions: Vulva; Atrophy
• Intervention / Treatment: Device: SmartXide2 treatment plus the application of Palingen cream; Device: Laser Therapy Only (Control Group)

Detailed Description

Sixty women participated in the study. Results showed that the combination treatment provided greater relief from discomfort and helped restore vaginal health, with fewer side effects. This approach may offer a safe and effective alternative for women who cannot use hormone-based therapies.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• San Marino
  • Borgo Maggiore
    • San Marino, Borgo Maggiore, San Marino, 47893
      • UOC di Ostetricia e Ginecologia, Ospedale di Stato della Repubblica di San Marino, Istituto per la Sicurezza Sociale (ISS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postmenopausal women with absence of menstrual cycle for at least 12 months, diagnosed with vulvovaginal atrophy (VVA) and presenting with related symptoms such as dryness, introital and deep dyspareunia, bleeding during intercourse, itching, or burning related to the severity of VVA, whether spontaneous or drug-induced (radio- or chemotherapy), either with a single symptom or a combination thereof.
• Age between 35 and 75 years;
• Patients unresponsive or dissatisfied with previous topical estrogen therapy, or presenting contraindications to the use of local and/or systemic estrogens.
• Previous negative Pap test performed within 3 years prior to study enrollment.

Exclusion Criteria:

• • Pregnancy or breastfeeding;

  • Presence of preneoplastic or neoplastic lesions of the cervix, vagina, or vulva;
  • Presence of active genital and/or urinary tract infection;
  • Relative or absolute dermatological contraindications to laser use;
  • Ongoing hormonal therapy (systemic or local);
  • Neurological and/or psychiatric disorders;
  • Chronic systemic autoimmune or metabolic diseases;
  • Refusal to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Active Comparator: Laser Therapy Only (Control Group); Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy. No additional topical treatment is applied. Laser sessions are performed at baseline (Day 0), Day 30, and Day 60. Follow-up visits include clinical evaluation and microbiome sampling at each time point.

Device: SmartXide2 treatment plus the application of Palingen cream; Patients will be randomized into two groups: one called the "control" group, in which patients will receive only the SmartXide2 treatment, and the second called "PALINGEN," in which patients will receive SmartXide2 treatment plus the application of Palingen cream.; Device: Laser Therapy Only (Control Group); Participants receive fractional CO₂ laser therapy according to the standard protocol for vulvo-vaginal atrophy. No additional topical treatment is applied. Laser sessions are performed at baseline (Day 0), Day 30, and Day 60. Follow-up visits include clinical evaluation and microbiome sampling at each time point.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in VVA (Vulvo-Vaginal Atrophy) symptoms	Assessed after 30 and 60 days of treatment using the Visual Analogue Scale (VAS). The VAS was used to quantify symptom intensity such as burning, dryness, itching, dyspareunia, and pain. Improvement was measured as the difference in VAS scores before and after treatment.	Outcome: Improvement in symptoms associated with vulvo-vaginal atrophy (VVA) Assessment Tool: Visual Analogue Scale (VAS) Time Frame: Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaginal Microbiome Composition	Analysis before and after 30 and 60 days of treatment. Parameters included: Biodiversity (Observed Operational Taxonomic Units, OTUs). Relative abundance of Lactobacillus genus and its species (L. crispatus, L. iners, etc.). Relative amounts of pathogenic bacteria (Gardnerella vaginalis, Atopobium vaginae, etc.).	Baseline (Day 0) - before treatment Visit 1 (Day 30) - after first month of treatment Visit 2 (Day 60) - after second month / end of treatment
Symptom improvement at intermediate time points	Comparison of VAS scores at Visit 1 (30 days) and Visit 2 (60 days) against baseline.	Baseline → Visit 1 (Day 30) Baseline → Visit 2 (Day 60)
Adverse Events Monitoring	Frequency and severity of side effects (e.g., redness, mild bleeding, burning, swelling) were recorded throughout the study.	Continuous from first laser session (Day 0) through 30 days and 60 days post-treatment

Collaborators and Investigators

• Sponsor: Institute for Social Security, Republic of San Marino

Publications and helpful links

General Publications

• Mueck AO, Ruan X, Prasauskas V, Grob P, Ortmann O. Treatment of vaginal atrophy with estriol and lactobacilli combination: a clinical review. Climacteric. 2018 Apr;21(2):140-147. doi: 10.1080/13697137.2017.1421923. Epub 2018 Jan 30.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Actual): October 1, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 24, 2025

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Vulva; Laser; Collagen; Atrophy; Modulation; Co2; Vulvo-vaginal; Theraphy; Collagen Cream
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Atrophy; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups
• Other Study ID Numbers: MF-01-24 1; N/1 (Other Identifier: UOC di Ostetricia e Ginecologia, Ospedale di Stato della Repubblica di San Marino, Istituto per la Sicurezza Sociale (I)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No