Efficacy and Safety of Laser Treatment in Vulvar Lichen Sclerosus: A Systematic Review

ABSTRACT

Objectives

This study systematically reviews randomized controlled trials (RCTs) evaluating laser therapy for vulvar lichen sclerosus (VLS) to assess its efficacy and safety, aiming to inform clinical management and guideline development.

Methods

RCTs on laser treatment for VLS were retrieved from PubMed, Embase, Web of Science, and Cochrane databases up to January 2025, limited to English literature. References from included studies were also screened. Data on study characteristics, laser parameters, outcome measures, measurement tools, and assessment time points were extracted and analyzed.

Results

Seven RCTs (332 patients) reported 19 outcomes and 19 measurement tools, each used a total of 28 times. Symptoms and signs were most frequently reported and commonly measured using the Visual Analog Scale (VAS). Most trials indicated improvements in symptoms, signs, quality of life (QoL), and histology after laser therapy. Three studies reported greater symptom/sign improvement than topical corticosteroids (p < 0.05), and three found higher patient satisfaction (p < 0.05). Two studies showed good tolerability via VAS. Adverse events occurred in five studies (147 patients), including five mild cases (local irritation, blisters, urinary tract infection, itching, and pain). Due to heterogeneity and low study quality, a meta‐analysis was not performed.

Conclusions

Laser therapy improves symptoms/signs, QoL, and histological outcomes in VLS, with good safety and tolerability. However, the evidence supporting its use as a monotherapy is limited, and benefits for anti‐inflammatory, anti‐fibrotic, scar‐preventive, or anticarcinogenic effects remain unproven. Large‐scale, long‐term, and high‐quality trials are needed, and future research should establish standardized Core Outcome and Measurement Sets to optimize VLS management.

Abbreviations

CG

control group

CSS

clinical scoring system for vulvar lichen sclerosus

LG

laser group

PGI‐I

patient global impressions scale—improvement

PGI‐S

patient global impressions scale—Severity

RCTs

randomized controlled trials

STD

standard deviation

VAS

Visual Analog Scale

VHI

vaginal health index

VLS

vulvar lichen sclerosus

VSQ

vulvovaginal symptom questionnaire

1. Introduction

Vulvar lichen sclerosus (VLS) is a chronic, inflammatory skin and mucosal disease primarily characterized by vulvar pruritus and/or pain, along with symptoms such as rough skin, depigmentation, fissures, atrophy, and adhesions. These manifestations often lead to functional impairments, including dyspareunia, significantly affecting the patient's quality of life (QoL) [1]. As the disease progresses, notable pathological changes occur. Early‐stage pathology is characterized by hyperkeratosis and irregular epidermal thickening, while later stages may exhibit a lighter‐colored homogeneous degeneration band in the superficial dermis, with vascular atrophy in the upper dermis and a reduction or disappearance of inflammatory cells [2, 3]. Additionally, VLS is a known risk factor for vulvar squamous cell carcinoma (VSCC), with an increased risk of malignancy ranging from 2% to 6% in untreated or inadequately treated cases [4, 5]. The pathogenesis of VLS remains unclear, but it is believed to be associated with inflammation, autoimmunity, hormonal imbalances, genetic factors, and chronic local irritation [6, 7]. Perimenopausal women are considered a high‐risk group, but recent trends show an increasing incidence of VLS in younger women [8]. Currently, common treatment options include topical medications, photodynamic therapy, and physical energy treatments. Topical corticosteroid therapy is widely recognized as the first‐line treatment for VLS. Guidelines recommend an ultra‐potent or potent agent, such as 0.05% clobetasol propionate ointment, once or twice daily for 3 months or in a tapering regimen—daily for 1 month, alternate days for 1 month, and then twice weekly for 1 month—followed by long‐term maintenance once or twice weekly, with lower‐potency corticosteroids (e.g., triamcinolone) as an option [9, 10]. However, treatment efficacy varies among individuals, and patient adherence is often poor.

Laser therapy has emerged as a novel physical treatment modality in recent years, including fractional CO₂ laser (FxCO₂), neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser, erbium‐doped yttrium aluminum garnet (Er:YAG) laser, and the combination of Er:YAG and Nd:YAG lasers. According to the 2024 EuroGuiderm Guideline on Lichen Sclerosus, FxCO₂ laser helps reduce hyperkeratosis but generally does not suppress inflammation, making it particularly effective in hyperkeratotic VLS cases; Nd:YAG laser may reduce inflammation and remodel collagen, aiding in softening sclerosis and reducing fissures; Combination Er:YAG and Nd:YAG therapy provides both superficial ablation and deep connective tissue regeneration [9]. The guideline does not specify clear indications for laser therapy, as it is currently under investigation and not considered a first‐ or second‐line treatment. Due to small sample sizes, heterogeneous protocols, overall low‐quality evidence, and uncertain efficacy, the guideline assigns a recommendation level of “No recommendation with respect to an intervention” for laser therapy in VLS [9]. Clinically, laser treatment has been explored for patients who respond poorly to first‐line treatment or have corticosteroid phobia, but its use remains experimental. Furthermore, the 2020 AUGS [11] safety advisory on energy‐based device (EBD) technologies highlighted a lack of sufficient evidence supporting the use of lasers and other energy devices for treating vulvovaginal symptoms associated with menopause, urinary incontinence, or sexual dysfunction. The safety and efficacy of these modalities remain uncertain, with potential serious safety risks.

Therefore, this study systematically analyzes RCTs on laser therapy for VLS to evaluate its efficacy and safety, aiming to provide a scientific rationale and evidence‐based medical support for clinical management. Additionally, this study synthesizes and summarizes outcome measures, assessment tools, and measurement time points reported in RCTs on VLS, laying the foundation for the future development of a consensus‐based Core Outcome Set (COS) and Core Outcome Measurement Set (COMS) specific to VLS. This will help enhance the standardization and normalization of evaluation methods in future clinical research and optimize their effectiveness.

2. Materials and Methods

This systematic review has been registered on the PROSPERO website (registration number CRD42024516497).

2.1. Inclusion and Exclusion Criteria

2.1.1. Inclusion Criteria

This review included: (1) RCTs on laser treatment for VLS; (2) Studies with patients diagnosed with VLS based on characteristic clinical manifestations or biopsy; (3) Studies providing patient demographics and data on diagnosis and treatment; and (4) Studies reporting treatment outcomes, side effects, and follow‐up.

2.1.2. Exclusion Criteria

This review excluded: (1) Nontherapeutic clinical studies; (2) Non‐randomized studies without a control group (CG) or those using a self‐controlled design; (3) Case reports; (4) Literature reviews and replication studies; and (5) Studies where the full text could not be obtained.

2.2. Data Sources and Searches

We conducted a search of PubMed, Embase, Web of Science, and Cochrane databases up to January 2025 to identify RCTs on the treatment of VLS. The search strategy incorporated both subject headings and free‐text keywords to identify potentially eligible studies (detailed search strings are provided in the Supporting Material). Reference lists from the included studies and relevant reviews were also examined to ensure exhaustive retrieval.

2.3. Study Selection

Initially, two researchers independently conduct a preliminary screening by reviewing the titles and abstracts and adhering to the predefined inclusion and exclusion criteria. Subsequently, they cross‐validate their findings. Following this, each researcher independently performs a secondary screening by thoroughly examining the full texts. The outcomes are cross‐checked once more to finalize the selection of literature. In the event of discrepancies and failure to achieve consensus through discussion between the two researchers, consultation with a third party is solicited.

2.4. Data Collection

We collected the following information from each eligible study:

(1) General study characteristics: first author, year of publication, source of the literature, country, funding source, conflicts of interest, and so forth.

(2) Study subject characteristics and interventions: sample size, demographics (age), intervention measures, control measures, treatment results, intervention duration, and so forth.

(3) Clinical outcomes, measurement instruments, and time points for outcome assessment.

2.5. Risk of Bias Assessment for the Included Studies

Two researchers rigorously appraise the methodological quality in the selected studies using the risk of bias evaluation tool provided in the Cochrane Handbook for RCTs. This tool comprises seven items: (1) correct randomization method; (2) implementation of allocation concealment; (3) blinding of participants and interveners; (4) blinding of outcome assessors; (5) completeness of outcome data and loss to follow‐up; (6) selective reporting of study results; and (7) other potential sources of bias. Subsequently, RCTs undergo quality assessment and are graded according to the criteria outlined in the Cochrane Handbook: A grade is assigned if all standards are fully met, indicating minimal bias risk; B grade is assigned if some standards are partially met, indicating moderate bias risk; and C grade is assigned if none of the standards are met, indicating high bias risk.

2.6. Data Analysis

Data were analyzed utilizing narrative synthesis methods, facilitating the examination of both qualitative and quantitative data derived from primary studies. The data were structured in tabular format, categorized by publication year, and complemented with essential methodological details, scale assessments, and findings. Meta‐analysis was not conducted due to anticipated methodological and clinical heterogeneity among studies, primarily stemming from disparities in intervention types, CGs, and outcome assessment variables.

3. Results

3.1. Baseline Characteristics of Included Studies

The literature screening process is illustrated in Figure 1. A preliminary search identified 1629 relevant articles. Following deduplication and review of abstracts and full texts, two researchers applied the inclusion and exclusion criteria, ultimately selecting seven English‐language studies. These studies involved 332 participants: 183 in the laser group (LG) and 149 in the CG. The LG included 20 cases of Nd:YAG laser, 47 cases of dual Nd:YAG/Er:YAG laser, and 116 cases of FxCO₂. The CG comprised 87 cases of topical corticosteroids, 13 cases of radiofrequency (RF) treatment, 20 cases of placebo laser, and 29 cases of FxCO₂ with low‐dose laser therapy. The included studies were primarily conducted in the United States, China, Switzerland, Brazil, Slovenia, and other countries. The basic characteristics of the studies are summarized in Table 1. Risk of bias is shown in Figure 2, with the assessment indicating a moderate risk and study quality rated as grade B. Blinding was not implemented for either researchers or participants in any study, except for the placebo LG [14].

Figure 1.

Flowchart for literature search process.

Table 1.

Baseline characteristics of the included studies.

Author	Country	Age (years)		Sample size (n)		Intervention	Results
		LG	CG	LG	CG
Ogrinc 2019 [12]	Slovenia	59 ± 10	57 ± 14	20	18	LG: Nd:YAG laser treatment CG: topical corticosteroids	Laser treatment discomfort averaged 1.5/10 on the VAS. At 1‐ and 3‐month follow‐ups, the laser group showed greater symptom improvement (burning, itching, pain, and dyspareunia), higher satisfaction, and greater sclerosis reduction than the corticosteroid group. Symptom improvement remained significant at 6 months. Before‐and‐after treatment photos were correctly ordered more often for laser‐treated patients than controls.
Burkett 2021 [13]	The United States	67.6 ± 11.0	61.5 ± 8.9	27	25	LG: FxCO2 CG: 0.05% clobetasol propionate cream	At 6 months, the laser group showed greater improvement in Skindex‐29 (11 points, p = 0.007), VSQ (−3.92 ± 4.12 vs. −0.58 ± 5.11, p = 0.014), and VHI (1.92 ± 4.34 vs. 0.43 ± 3.62, p = 0.046). VAS scores were similar between groups. PGI‐I: 89% of laser patients reported improvement versus 62% in the steroid group (p = 0.07). PGI‐S: 81% of laser patients were satisfied versus 41% in the steroid group (p = 0.01). Skindex‐29 improvement was significant only in those previously treated with steroids.
Mitchell 2021 [14]	The United States	59	59	19	20	LG: FxCO2 laser therapy CG: sham laser	Histopathology scale score: 0.2 reduction (improvement) in active group (95% CI −1.1, 0.80, p = 0.74), front 0.1 increase in sham group (95% CI −0.90, 1.0, p = 0.91). Difference not statistically significant in the ITT analysis (−0.2; 95% CI −1.14, 1.06, p = 0.76). CCS: 7.10‐point reduction in active arm (95% CI −13.2, −1.1, p = 0.02); 4.80‐point reduction in sham group (95% CI −9.50, −0.20, p = 0.04). Difference not statistically significant p = 0.60. In the physicians' point CSS, there was a 0.70 increase (worsening) in the active (95% CI −0.80, 2.1, p = 0.36) and a 0.30 reduction in the sham group (95% CI −1.7, 1.2, p = 0.70).
Jingqiu Guo 2022 [15]	China	N/R	N/R	25	(1) 13 (2) 12	LG: FxCO2 laser CG: (1) RF；(2) 0.05% clobetasol propionate cream and soaking with Chinese patent medicine	Topical corticosteroids and traditional Chinese medicine can quickly relieve itching symptoms in patients, but it cannot significantly improve skin elasticity, skin color, and lesion scope, and VLS easily relapses after treatment. Radiofrequency can improve itching symptoms and skin color but has poor effects on the change of skin elasticity and lesion scope. Multi‐focused laser treatment can alleviate the degree of pruritus, improve skin color and elasticity, and narrow the lesion scope, and VLS will not relapse within 3 months after treatment.
Salgado 2023 [16]	Brazil	N/R	N/R	11	9	LG: FxCO2 CG: 0.05% clobetasol propionate cream	The clinical/anatomical characteristics of the vulva did not differ between the treatment groups, as much before as after its performance. There was no statistically significant difference between the treatments performed regarding the impact on the quality of life of the patients. A higher degree of satisfaction with the treatment was obtained among the patients in the laser group in the third month of evaluation. Laser therapy also revealed a higher occurrence of telangiectasia after treatment completion.
Krause 2023 [17]	Switzerland	50	53	34	29	LG: FxCO2 with normal dose laser therapy (24 W) CG: FxCO2 with low‐dose laser therapy (0.5 W)	Low energy density may improve LS; no significant difference was observed between the groups.
Zivanovic 2024 [18]	Switzerland	57.9 ± 16.4	62.2 ± 14.4	47	23	LG: dual Nd:YAG/Er:YAG laser therapy CG: topical clobetasol 0.05% ointment or cream	The total LS score decreased by −2.34 ± 1.20 in women treated with laser compared with a decrease of −0.95 ± 0.90 in those receiving steroid applications (p < 0.001). Laser treatment was safe and well‐tolerated. Subjective severity scores and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035).

Abbreviations: CG: control group; Er:YAG: erbium‐doped yttrium aluminum garnet; FxCO₂: fractional CO₂ laser; LG: laser group; N/R: not reported; Nd:YAG: neodymium‐doped yttrium aluminum garnet; RF: radiofrequency.

Figure 2.

Risk of bias assessment of included studies. A. Overall proportion of risk of bias in included studies; B. Risk of bias assessment for each study. (1) Random sequence generation; (2) Allocation concealment; (3) Blinding of participants and personnel; (4) Blinding of outcome assessment; (5) Incomplete outcome data; (6) Selective reporting; and (7) Other bias.

Table 2 outlines the treatment cycles, laser types, and energy parameters used in the included studies. Notably, there was considerable variation in treatment cycles, ranging from three to five sessions, with three treatments being the most common (5/7). Five studies employed FxCO₂ lasers, with specific parameters including power of 18–26 W, exposure time of 300–1000 µs, and spacing of 250–1200 nm.

Table 2.

Laser energy parameters and treatment‐related adverse events.

Author	Treatment duration	Laser type	Energy parameters	Adverse event
Burkett 2021 [13]	Once every 4–6 weeks, a total of 3 sessions	FxCO2	26 W, 800 µs, 800 µm	Minor burning and blistering at the laser site (1/27)
Mitchell 2021 [14]	5 sessions within 24 weeks	FxCO2	Power, 18–26 W; Stack, 1; Time, 800–1000 µs; Spacing, 1000–1200 nm	Complaints of transient, mild discomfort; no adverse events were reported
Salgado 2023 [16]	3 sessions, 30‐day intervals	FxCO2	Power, 25 W; Stack, 1; Time, 700 µs; Spacing, 700 nm	/
Jingqiu Guo 2022 [15]	Monthly, 3 sessions per course	FxCO2	40–50 mJ/pixel; Time, 300–400 µs; DOT spacing, 250–400 µm	/
Krause 2023 [17]	3 weekly sessions over 18 weeks	FxCO2	Power 24 W; exposure time 400 µs; DOT spacing, 1000.	No significant discomfort or side effects were reported
Zivanovic 2024 [18]	4 sessions at baseline, 1, 2, and 4 months	dual Nd:YAG/Er:YAG	Nd: R33 handpiece/9‐mm spot size. The laser was set to PIANO mode (long 5‐s pulses), 70–100 J/cm2 fluence Er: R11 handpiece/5‐mm spot size 1–3 J/cm2 fluence.	No serious adverse events related to the laser treatment were encountered, and complications were minor and transient. Within the first week after laser treatment, only 2.3% (4/176) reported adverse events: one urinary tract infection, two vulvar itching, and one vulvar pain.
Ogrinc 2019 [12]	3 Nd:YAG sessions, 14‐day intervals	Nd: YAG	Using the R33 noncontact handpiece with a 9‐mm spot size, piano pulse mode (5 s), and 90 J/cm2 fluence.	No adverse effects were observed or reported, and there was no new disease on follow‐up local gynecological examination.

Abbreviations: Er:YAG, erbium‐doped yttrium aluminum garnet; FxCO₂, fractional CO₂ laser; Nd:YAG, neodymium‐doped yttrium aluminum garnet.

3.2. Clinical Outcomes and Assessment Tools

Among the seven studies, 19 clinical outcomes were reported, with 28 instances of use: 14 patient‐reported outcomes (PROs), 9 clinician‐reported outcomes (ClinROs), and 5 co‐reported outcomes by both clinicians and patients. Due to substantial heterogeneity, outcomes were classified while preserving their original intent, under the categories of histology, symptoms/signs, treatment efficacy, sexual function, QoL, patient satisfaction, and tolerability. Outcomes related to symptoms/signs and histology served as the primary efficacy endpoints in clinical trials of VLS, with symptoms/signs being the most frequently reported outcomes in the included studies.

The 7 RCTs used 19 different tools across 28 instances, with the Visual Analog Scale (VAS) being the most common, though its purpose varied. Fifteen tools (78.94%) were used only once (Table 3). Most measurements were taken at 6 months posttreatment, with the longest follow‐up at 1 year, and no long‐term data were available.

Table 3.

Use of clinical outcomes and measurement instruments in studies on laser treatment of VLS.

Outcome domain	Outcomes	COA	Outcome classification	Tools	Measurement time points	Studies that used the tool
Histology	Clinical/anatomical characteristics of the vulva	ClinRO	/	Vulva biopsy	Baseline, 1 year	Salgado 2023 [16]
	Change in the histopathology scale score	ClinRO	Primary	Biopsy (0–6 scale)	Baseline, 8 weeks	Mitchell 2021 [14]
	Thickness of sclerosis, thickness of the epidermis, and the degree of inflammation	ClinRO	Secondary	Biopsies, four‐point scale	Baseline, 3 months	Ogrinc 2019 [12]
Symptoms/Signs	Symptoms	ClinRO	Secondary	CSS	Baseline, 8 weeks	Mitchell 2021 [14]
	Symptom bother	PRO	Primary	VAS	Baseline, 6 weeks, 12 weeks	Krause 2023 [17]
	Symptoms, treatment satisfaction, and the degree of difficulty in performing it	ClinRO + PRO	/	DQ	Baseline, 1 year	Salgado 2023 [16]
	Symptoms	ClinRO	Primary	LS score	Baseline, 6 months	Zivanovic 2024 [18]
	Symptoms	ClinRO	Secondary	Lichen score	Baseline, 6 weeks, 12 weeks	Krause 2023 [17]
	The pruritus degree; Skin elasticity; Skin color; Lesion scope; Total score	ClinRO + PRO	/	DS	Baseline, 1 month, 3 months	Jingqiu Guo 2022 [15]
	Subjective symptoms intensity	PRO	Secondary	VAS	Baseline, 6 months	Zivanovic 2024 [18]
	Vulvovaginal symptoms	PRO	Secondary	VSQ	Baseline, 6 months	Zivanovic 2024 [18]
	Acute dermatologic symptoms	ClinRO + PRO	Primary	Skindex‐29 score	Baseline, 6 months	Burkett 2021 [13]
	Symptoms	PRO	Secondary	Subjective VAS	Baseline, 6 months	Burkett 2021 [13]
	Visual appearance	ClinRO	Secondary	Objective VAS	Baseline, 6 months	Burkett 2021 [13]
	Vaginal health	ClinRO	Secondary	VHI	Baseline, 6 months	Burkett 2021 [13]
	Burning, itching, and pain	PRO	Primary	VAS	Baseline, 1 month, 3 months, 6 months	Ogrinc 2019 [12]
Treatment efficacy	Treatment efficacy	ClinRO	Secondary	Clinical photographs	Baseline, 3 months	Ogrinc 2019 [12]
Sexual function	Sexual function	PRO	Secondary	FSFI	Baseline, 6 weeks, 12 weeks	Krause 2023 [17]
	Lack of sensation during intercourse, anorgasmia, and dyspareunia	PRO	Secondary	DQ	Baseline, 1 month, 3 months, 6 months	Ogrinc 2019 [12]
QoL	Quality of life	PRO	/	Life quality questionnaire	Baseline, 1 year	Salgado 2023 [18]
	Quality of life	PRO	Secondary	DQ	Baseline, 6 weeks, 12 weeks	Krause 2023 [17]
	Quality of life	PRO	Secondary	VSQ	Baseline, 6 months	Burkett 2021 [13]
Patient satisfaction	Patient satisfaction	PRO	Secondary	PGI	6 months	Zivanovic 2024 [18]
	Patient satisfaction	PRO	Secondary	PGI‐I	6 months	Burkett 2021 [13]
	Patient satisfaction	PRO	Secondary	PGI‐S	6 months	Burkett 2021 [13]
	Treatment satisfaction	PRO	Secondary	DS	3 months	Ogrinc 2019 [12]
Tolerability	Tolerability	ClinRO + PRO	Secondary	VAS	After each treatment	Zivanovic 2024 [18]
	Tolerability	ClinRO + PRO	Secondary	VAS	After each treatment	Ogrinc 2019 [12]

Abbreviations: CSS: clinical scoring system for vulvar lichen sclerosus; DQ, designed questionnaire; DS, designed scale; PGI‐I, Patient Global Impressions scale—Improvement; PGI‐S, patient global impressions scale—Severity; VAS, Visual Analog Scale; VHI: vaginal health index; VSQ, vulvovaginal symptom questionnaire.

3.3. Efficacy and Safety Evaluation

3.3.1. Efficacy

3.3.1.1. Symptoms and Signs

Tables 1 and 3 summarize the evaluation methods and findings of the included studies. All seven studies reported outcomes related to symptoms and signs. Five studies used topical corticosteroid therapy as the CG, with three showing significant improvement in symptoms and signs in the LG compared to the CG. Specifically, Ogrinc [12] found that both groups showed reduced symptom severity (burning, itching, pain, and dyspareunia) at 1 and 3 months of follow‐up compared to baseline, with the LG showing significantly greater improvements (p < 0.01). At the 6‐month follow‐up, the LG exhibited significant improvements in burning (4.4 point effect size, 95% CI 2.4–6.5, p < 0.001), itching (4.9 point effect size, 95% CI 2.4–7.4, p = 0.001), and pain (5.4 point effect size, 95% CI 3.3–7.5, p < 0.001). Burkett [13] demonstrated that the LG had a greater improvement in Skindex‐29 scores (10.9 point, 95% CI 3.42–18.41; p = 0.007) compared to 0.05% clobetasol cream, with the greatest improvements in emotion and symptoms aspects (12.86 point, 95% CI 3.38–22.34; p = 0.011; 16.12 point, 95% CI 6.33–25.91 years; p = 0.002). Guo et al. [15] found that FxCO₂ laser treatment significantly improved itching (p = 0.000), skin elasticity (p = 0.000), color (p = 0.000), and lesion area (p = 0.001), with no relapse within 3 months, while topical corticosteroids therapy and Chinese medicine showed less effectiveness. Two remaining studies found no significant differences between the laser and clobetasol groups in symptoms and signs improvement. Specifically, Salgado et al. [16] developed a questionnaire to assess symptom improvement, finding no significant difference between the groups. Zivanovic [18] reported similar subjective severity scores (VAS for itching, burning, and pain) and vulvar vaginal symptom questionnaire (VSQ) scores between the laser and clobetasol groups, with no significant differences in either measure.

Two additional studies compared the laser to a placebo and examined the effects of different CO₂ laser doses. Mitchell et al. [14] found no significant differences between the laser and placebo groups in patients' subjective or clinicians' objective sections of the CSS scores, the latter assessing fissures, erosions, hyperkeratosis, agglutination, stenosis, and atrophy. However, the LG showed significant improvement in the patients' subjective section of the CSS (pruritus, soreness, burning, and dyspareunia) at 2 months posttreatment compared to baseline (−7.10, 95% CI −13.2, −1.1, p = 0.02). Krause et al. [17] found that both low‐dose and normal‐dose CO₂ LGs had significantly reduced VAS scores at 18 weeks posttreatment (p < 0.0001), though no significant differences were observed between the doses at the 3‐month follow‐up regarding vulvar discomfort (p = 0.6244). Salgado et al. [16] reported no significant differences between the FxCO₂ laser and clobetasol groups at 2 months posttreatment in clinical and anatomical features, including extension of the disease, fissures, hypochromia, skin thinning, ulceration, elasticity loss, sclerosis, telangiectasia, clitoral burial, labial resorption, vaginal introitus narrowing, urethral occlusion, perianal compromise, and synechia. However, significant differences were noted in hyperkeratosis (p = 0.024), lichenification (p = 0.027), and excoriation (p = 0.038).

3.3.1.2. QoL

Three studies assessed QoL, including two comparing laser treatment with topical corticosteroid therapy and one comparing different CO₂ laser doses. Burkett et al. [13] used the VSQ questionnaire and found significant improvement in the LG at 6 months posttreatment compared to the steroid group (3.34, 95% CI 0.68–6.00, p = 0.014). Salgado et al. [16] used the WHOQOL‐BREF questionnaire and found no significant difference between the laser and clobetasol groups at 12‐month follow‐up. Krause et al. [17] assessed QoL with the question, “How has your quality of life concerning lichen developed since last time?” and found no significant difference between the low‐ and high‐dose LGs at 12 weeks posttreatment (p = 0.80).

3.3.1.3. Histology

Two studies assessed histology, with one comparing laser (Nd:YAG, FxCO₂ laser) versus topical steroid treatment, and the other comparing FxCO₂ laser versus sham laser treatment. Mitchell et al. [14] reported a 0.20 reduction (improvement) in histopathology scale scores from baseline in the active treatment group (95% CI −1.1 to 0.80, p = 0.74) and a 0.1 increase in the sham group (95% CI −0.90 to 1.0, p = 0.91). The change in histopathology scale scores, including loss of rete pegs, dermal homogenization, and chronic inflammation, was not statistically significant between the two groups (95% CI −1.14 to 1.06, p = 0.76). Ogrinc et al. [12] found a significant reduction in sclerosis thickness in the Nd:YAG LG (−0.67 mm; 95% CI −0.99 to −0.34 mm; p = 0.009), while no significant change was observed in the corticosteroid group (−0.10 mm; 95% CI −0.48 to 0.20 mm; p = 0.577). No significant differences were observed in epidermal thickness or inflammation changes within or between the groups.

3.3.1.4. Patient Satisfaction

Three studies evaluated patient satisfaction, all comparing laser treatment with topical steroids, with all showing higher satisfaction in the LG. Ogrinc et al. [12] used a 4‐point scale to assess satisfaction and found that, at the 3‐month follow‐up, the LG had significantly higher satisfaction compared to the CG (χ ² = 36.4; p < 0.001). Burkett et al. [13] assessed satisfaction with the PGI‐I and PGI‐S scales and found no significant difference in PGI‐I (4.72, 95% CI 1.15–24.55; p = 0.073), but a significant difference in PGI‐S (6.07, 95% CI 1.75–24.01; p = 0.011). Zivanovic et al. [18], using the PGI‐I scale, reported higher satisfaction in the LG at the 6‐month follow‐up (p = 0.035).

3.3.2. Safety

3.3.2.1. Tolerability and Adverse Events

Two studies used the VAS to assess tolerability, both reporting favorable outcomes for laser treatment. Table 2 summarizes data from five studies (147 participants) on adverse reactions [12, 13, 14, 17, 18]. Five patients (5/147) reported mild adverse effects, including one case each of local skin irritation, blistering, and urinary tract infection, and two cases of vulvar itching, as well as one case of vulvar pain.

4. Discussion

4.1. Main Findings

Most RCTs suggest that laser treatment improves symptoms, signs, QoL, and histology compared to baseline measurements. Three studies demonstrated that the LG had greater improvements than the steroid group in aspects such as burning, itching, pain, dyspareunia, emotion, skin elasticity, color, lesion area, and soreness. One study found that laser treatment significantly improved hyperkeratosis, lichenification, and excoriation compared to topical corticosteroids after 3 months of treatment. Patient satisfaction was higher with laser treatment in three studies. Tolerability, assessed with the VAS in two studies, showed favorable outcomes. Five studies involving 147 patients reported mild adverse effects in 5 patients (3%), including local skin irritation, blisters, urinary tract infection, vulvar itching, and vulvar pain. These results indicate that laser treatment for VLS is relatively safe, well‐tolerated, and highly satisfactory for patients. Histological outcomes showed that Nd:YAG laser improved vulvar skin sclerosis compared to steroids, though no significant differences were found in epidermal thickness or inflammation. Conversely, CO₂ laser treatment did not significantly affect rete peg loss, dermal homogenization, or inflammation. Given the anti‐inflammatory and anti‐fibrotic properties of potent corticosteroids [9, 19], their use remains necessary during laser therapy to prevent architectural changes and carcinoma development. Consistent with the 2024 ISSVD Practical Guide to Diagnosis and Management of Lichen Sclerosus [10], there remains insufficient objective evidence to confirm that laser therapy, as an alternative to topical steroids, can prevent architectural changes or reduce the risk of VSCC. For biopsy‐proven benign lesions unresponsive to maximal medical therapy, laser may be used adjunctively with topical corticosteroids to enhance absorption, control inflammation, and prevent or delay hyperkeratosis recurrence [10].

Based on the present findings, outcome measures and assessment tools for VLS remain highly heterogeneous. Across seven RCTs, 19 distinct outcomes and 19 measurement tools were used 28 times each in total, of which 15 tools (78.94%) appeared only once. The lack of a standardized COS and COMS hampers comparability across studies, limiting data synthesis and obstructing the generation of high‐level evidence [20, 21]. Moreover, the included studies predominantly focus on symptoms, with limited attention to histology and cytopathology. The 2024 ISSVD Practical Guide [10] similarly notes that most studies on alternatives to TCs have major design flaws, relying on subjective rather than objective measures and short‐term follow‐up. Without consensus‐based COS for clinical signs, symptoms, and QoL, trials are unlikely to adequately address efficacy, harms, and durability. Given that VLS‐related inflammation can cause scarring, architectural distortion, functional impairment, and an increased risk of malignancy, treatments that only address symptoms without reversing histopathological changes are insufficient. The U.S. Food and Drug Administration (FDA) requires histopathological improvements as a primary endpoint for investigational new drug application [14], and any new treatment for VLS should also prioritize these changes as a paramount outcome.

4.2. Comparison With Other Studies

In a 2021 systematic review, the Tasker's research group examined laser therapy for genital lichen sclerosus across men, women, and children, including six RCTs, one non‐randomized trial, nine single‐arm trials, and eight case series [22]. Similarly, Gill‐Villalba et al. reviewed studies on laser therapy for VLS published before April 2023 [23]. In contrast, the present study specifically focuses on VLS in women, offering a more comprehensive analysis of all reported RCTs on laser therapy for VLS up to January 2025. This study includes a larger body of literature, encompassing more studies and patients. Additionally, it systematically analyzes current practices in the clinical outcomes reported across the included RCTs, as well as the tools and time points used for outcome assessment, offering a comprehensive summary of results within these categories.

4.3. Implications for Practice

Current RCTs are constrained by small sample sizes, all being single‐center with relatively few participants. Future clinical trials should aim for larger, multicenter cohorts and improved research quality. Current evidence does not support laser therapy as a sole treatment for VLS, with local anti‐inflammatory treatment remaining essential. Moreover, high‐quality RCTs investigating the combination of topical corticosteroids and laser therapy for VLS are lacking, warranting further clinical exploration. Existing studies exhibit considerable variability in clinical outcomes and measurement tools, with a notable absence of relevant biological markers. Additionally, most studies have short follow‐up periods, primarily within 6 months, with the longest being 1 year. Future research should establish a comprehensive COS and COMS encompassing all VLS characteristics and identify optimal time points for efficacy assessment. This will help standardize future studies, providing robust evidence‐based support for the long‐term management of VLS.

4.4. Strength and Limitations

This study's strength lies in its comprehensive review of all published RCTs on laser therapy for VLS in women up to January 2025. It analyzed the clinical outcomes, measurement tools, and assessment time points reported across the included RCTs and conducted a systematic evaluation of their effectiveness and safety. This analysis provides evidence‐based support for laser therapy in treating VLS and contributes to the standardization of evaluation methods in future clinical research. The study's limitations include: (1) a limited number of large RCTs, all of which are single‐center and small‐sample RCTs and (2) significant heterogeneity in clinical outcomes and assessment tools, which precluded meta‐analysis.

5. Conclusion

In conclusion, most current RCTs indicate that laser therapy improves symptoms/signs (such as burning, itching, pain, dyspareunia, skin elasticity, and soreness), QoL (including emotional, life, and sexual impacts), and histological outcomes (e.g., changes in vulvar skin sclerosis) in VLS patients, with favorable tolerability and safety profiles. However, given the limited number of relevant RCTs, further research should prioritize rigorous, large‐scale, multicenter, and long‐term studies to further confirm the efficacy and safety of this treatment. Furthermore, there is no evidence to support that laser therapy offers anti‐inflammatory, anti‐fibrotic, structural preservation, scar prevention, or anticarcinogenic benefits for VLS, precluding its recommendation as a sole therapeutic approach. Future studies should strengthen the evidence regarding the potential effects of laser therapy, both as monotherapy and in combination with topical corticosteroids. Additionally, establishing a specific and comprehensive COS and COMS for VLS is essential to standardize future research and enhance the diagnosis, treatment, and management of this condition.

Author Contributions

Dongmei Wei: conceptualization, data curation, formal analysis, investigation, methodology, validation, writing – original draft. Jian Meng: conceptualization, data‐curation, formal analysis, investigation, methodology, writing – review and editing. Qiao Li: data curation, investigation, validation, writing – review and editing. Yueyue Chen: formal analysis, methodology, supervision, writing – review and editing. Yajing Wang: methodology, supervision, writing – review and editing. Xiaoyu Niu: conceptualization, methodology, formal analysis, supervision, project administration, writing – review and editing.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting Material Appendix‐8.12.

Wei D., Meng J., Li Q., Wang Y., Chen Y., and Niu X., “Efficacy and Safety of Laser Treatment in Vulvar Lichen Sclerosus: A Systematic Review,” Lasers in Surgery and Medicine 57 (2025): 760–770. 10.1002/lsm.70062.