Two-Year Outcomes of Fractional CO₂ Laser for Vaginal Laxity: Effectiveness, Retreatment Need

Abstract

Objective

The purpose of this study was to evaluate the long-term efficacy of fractional CO₂ laser in the treatment of vaginal laxity (VL) and to determine additional treatment requirements during two-year follow-up.

Methods

A total of 176 women who underwent fractional CO₂ laser therapy for vaginal laxity between January 2020 and January 2023 were retrospectively evaluated. Three sessions of laser therapy were applied at 4–6 week intervals in all cases. Primary outcome measures were additional laser therapy requirements, patient satisfaction with primary and secondary treatments, and the general clinical effect of laser therapy on VL. Secondary outcomes included the evaluation of genital self-image, sexual function, urinary symptoms, and vulvovaginal complaints assessed using the following five validated measurement tools: the Patient Global Impression of Improvement (PGI-I), Michigan Incontinence Symptom Index (MISI), Female Sexual Function Index (FSFI), Vulvovaginal Symptoms Questionnaire (VSQ), and Female Genital Self-Image Scale (FGSIS).

Results

Additional laser therapy requirements occurred in 33.5% of patients at the end of two-year follow-up. Significant levels of improvement were determined in all FSFI, FGSIS, PGI-I, MISI, and VSQ scores following completion of the first treatment series (p < 0.001). A marked increase was observed in FSFI total scores and the arousal subdomain, while orgasm decreased significantly at the end of the second application compared to the first (p < 0.05). The increase in FGSIS scores showed that genital self-image improved consistently following both the first and second applications. PGI-I data revealed high post-treatment patient satisfaction (p < 0.001). In addition, the MISI and VSQ scores showed that urinary symptoms and vulvovaginal discomfort decreased significantly following both the initial treatment and second application. However, the marked initial clinical benefit tended to decrease over time, and additional intervention requirements increased one year after the first treatment.

Conclusion

Fractional CO₂ laser therapy provides significant and clinically important improvement in the management of VL. The positive effects recorded in post-treatment sexual function, genital self-image, and vaginal symptoms are significantly preserved during the first year. However, due to the gradual decrease in the effects, we recommend the application of a second laser session approximately one year following the first treatment series in order to enhance the continuity of the therapeutic benefit.

Introduction

The use of laser technology in gynecology has become an important area of development in recent years. Laser-based devices (LBDs) employed in that context represent systems that operate on the principle of light amplification via stimulated light emission. LBDs produce short-duration micro-pulses that target mucosal tissue, each session lasting only a few minutes. Controlled heating of connective tissue in the vaginal wall triggers collagen contraction, the synthesis of new collagen, and increased vascularization. Biopsies show that laser application increases new collagen formation and neovascularization in the vaginal mucosa [1]. These effects combine to support regeneration in the vaginal epithelium [2].

LBDs have become increasingly used by gynecologists due to their ease of application, short procedure times under outpatient conditions, and being well tolerated by patients. However, their high costs and the fact they are not covered by insurance represent a significant limitation. Nevertheless, despite its high cost, laser technology is effectively employed in the management of various gynecological conditions, such as vaginal laxity (VL) [3]. This laxity is characterized by a loss of tone in vaginal tissue in association with childbirth trauma or aging and can adversely affect sexual satisfaction and quality of life. VL can affect all age groups. The prevalence ranges between 2 and 48%, depending on age, ethnicity, cultural factors, body perception, and reporting methods [3].

Recent randomized controlled studies assessing the efficacy of laser therapies have shown that fractional CO₂ laser can improve tissue quality by establishing a controlled thermal effect in the vaginal mucosa, but that this effect decreases over time and additional applications may be required [4, 5]. Prospective studies from 2022–2024 report that laser applications yield significant improvements in genital self-perception, sexual function, and vulvovaginal symptoms in the short term, but that the long-term response may vary depending on patient characteristics. Research has also emphasized that increasing collagen in pelvic floor support tissue through laser-induced tissue remodeling may yield potential benefits, not solely in VL, but also in additional indications such as stress incontinence and vulvar tissue aging [6, 7]. In addition, recent systematic reviews have shown that the safety profile of laser therapies is generally good, although further larger scale studies are needed to determine standardized protocols, long-term follow-up data, and optimal care intervals. Recent systematic reviews have reported short-term symptomatic improvement following laser-based therapies for vaginal laxity; however, the overall quality of evidence remains low and long-term data are limited [8].

All current findings support the idea that vaginal laser therapies are promising in terms of symptomatic improvement, although important information gaps still remain on the subjects of the therapeutic effect duration, the need for re-application, and long-term clinical results. Despite the increasing spread of laser use, two-year and longer follow-up data in the literature are scarce. The present study was therefore performed to evaluate the efficacy of fractional CO₂ laser in the treatment of VL over a two-year follow-up period. The original aspect of this study involves its systematic examination of the effectiveness of primary and secondary laser applications using validated evaluation scales and its examination of the long-term treatment response.

Materials and Methods

This single-center, retrospective study was performed at a secondary health center in Türkiye between January 2020 and January 2023. Approval for the study protocol was granted by the local institutional ethical committee (E-46059653–050.99–251,446,959), and all research procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki. Participation was on an entirely voluntary basis, written informed consent being obtained from all patients prior to treatment. All laser procedures were performed on a self-pay basis, and no financial support was provided by the hospital or device manufacturers.

Women aged 20–60 who presented due to VL and who underwent fractional CO₂ laser therapy during the specified period were included in the study. This age range was specifically selected as the period when loss of connective tissue elasticity associated with birth traumas and age become evident. Patients with malignancies, concurrent pelvic floor diseases, requiring surgical treatment, with complex genital pathologies, or with histories of previous unsuccessful laser therapy or surgical intervention were excluded. Pelvic organ prolapse was assessed clinically. Patients with advanced prolapse (≥ stage 3) were excluded, while mild anterior compartment laxity (stage 1–2) was allowed, consistent with typical vaginal laxity presentations. Vaginal laxity was diagnosed based on patient-reported symptoms, including perceived vaginal looseness, reduced vaginal tightness during intercourse, and decreased sexual friction. Given the lack of a standardized objective diagnostic tool, VL diagnosis was primarily symptom-based and supported by clinical examination findings. The degree of vaginal laxity was assessed during gynecological examination and categorized as mild, moderate, or severe based on vaginal tone, tissue resistance, and examiner assessment. This grading was used for descriptive purposes only and was not included as a primary or secondary outcome measure. The analysis was thus structured such as to permit the evaluation of laser response in the treatment of VL in a homogeneous population. Of the 176 patients included in the study, complete baseline demographic and clinical data were available for 136 patients. The remaining 40 patients had missing baseline variables and were therefore excluded from analyses requiring complete baseline data. However, all 176 patients were included in longitudinal outcome analyses where follow-up data were available.

The MonaLisa Touch SmartXide2 C60 (V2LR, DEKA, Italy) laser system was employed in treatment. This features fractional CO₂ technology intended to stimulate collagen contraction and neocollagenesis by applying controlled thermal damage in mucosal tissue. No special pre-procedural preparation of anesthesia is required, gentle vaginal drying with a sterile compress being sufficient when needed. Transvaginal laser was applied to all patients with 40 W power, a 1000 µs dwell time, and dot spacing parameters adapted to the indication (700 µm for VL; 1000 µm for genitourinary syndrome of menopause). Two consecutive shots were fired at each level at the 11.00 and 13.00 positions, the entire vaginal canal being scanned equally with a probe capable of rotating 360°. The SmartStack 1–2 protocol was applied in the first session, and the SmartStack 2–3 protocol in the second and third sessions. Three sessions of treatment were applied to all patients at intervals of 4–6 weeks. Parameters were selected according to previous studies evaluating fractional CO₂ for VL. Patients were advised to avoid sexual relations for five days following each laser application. Control evaluations were performed one, 12, and 24 months after the final laser session.

The primary outcome measure of this study was the evaluation of additional laser therapy requirements during two-year follow-up. Retreatment (“second application”) was not scheduled a priori but was offered based on clinical need during follow-up. Patients were evaluated at routine visits at 12 and 24 months after the initial treatment series. A second laser application was recommended to patients who reported a subjective decline in symptom improvement, recurrence of vaginal looseness, or reduced sexual satisfaction compared with their post-treatment status, and who requested further treatment. The majority of second applications were performed approximately 12 months after the initial treatment, corresponding to the period when a gradual decrease in clinical benefit was most frequently observed. Patient satisfaction and the rate of improvement in VL symptoms following the first and second laser applications were also analyzed. Secondary outcomes included the evaluation of the effects of laser therapy on genital self-image, sexual function, and urinary symptoms. Five validated tools were utilized to measure these specific outcomes:

1) Patient Global Impression of Improvement (PGI-I) [9]: The PGI-I is a scale designed to assess patient satisfaction by asking these to rate their current condition compared to pretreatment on a scale ranging from 1 (indicating "very much better") to 7 (indicating "very much worse".) In accordance with current recommendations, PGI-I scores of 1 (“very much better”) and 2 (“much better”) were considered indicative of treatment success. PGI-I scores were analyzed descriptively and were not used as a primary endpoint.

2) The Michigan Incontinence Symptom Index (MISI) [10]: The MISI uses a Likert-type scale to measure urinary incontinence and its impact on quality of life. Consisting of 10 items, the MISI total score encompasses three subdomains: stress urinary incontinence (items 1–3), urge urinary incontinence (items 4–6), pad usage (items 7–8), and a distinct bother domain (items 9–10). Higher scores reflect more severe symptoms and greater bother.

3) Female Sexual Function Index (FSFI) [10]: The FSFI evaluates female sexual function over the previous four weeks through 19 items grouped into six domains: desire (items 1–2), arousal (items 3–6), lubrication (items 7–10), orgasm (items 11–13), satisfaction (items 14–16), and pain (items 17–19).

4) Vulvovaginal Symptoms Questionnaire (VSQ) [11]: VSQ evaluates vulvovaginal symptoms experienced over the previous week. It consists of 21 items distributed across four subscales: symptoms (items 1–7), emotions (items 8–11), life impact (items 12–15), and sexual impact (items 16–21). Each item is scored dichotomously as "Yes" or "No," with higher total and subscale scores indicating greater vulvovaginal symptom bother.

5) Female Genital Self-Image Scale (FGSIS) [12]: Utilizing a seven-item, 4-point response scale (strongly agree, agree, disagree, strongly disagree), the FGSIS assesses women's perceptions of their own genitals. Total scores range from 7 to 28, with higher scores indicating a more positive genital self-image.

Statistical Package for the Social Sciences (SPSS) version 25 was used for data analysis. The normality of distributions was assessed using the Shapiro–Wilk test. The Wilcoxon test was employed when normal distribution was not observed within two dependent groups. Conversely, a paired-samples t test was applied if normal distribution was detected within the two groups. Results were presented as mean (± standard deviation [SD]) for normally distributed data, and as median (25th-75th percentile) values for non-normally distributed data. The chi-square test was applied in the comparison of independent categorical variables, and the results were reported as numbers and percentages. Statistical significance was set at p < 0.05. Missing data were handled using complete-case analysis for baseline characteristics, while longitudinal analyses included all available data at each time point.

For longitudinal comparisons across multiple time points, repeated-measures analyses were performed. Friedman tests were used for non-normally distributed variables and repeated-measures ANOVA for normally distributed variables. Post-hoc multiple comparison procedures (Dunn’s test or Newman–Keuls test, as appropriate) were applied following global tests to control for multiple comparisons.

Results

One hundred seventy-six patients with a mean age of 38.67 ± 7.38 years and a median parity of 3.00 [2.00–3.00] were enrolled in the study. The median number of previous vaginal births was 2.00 [1.25–3.00], while the median number of previous cesarean births was 0.00 [0.00–1.00]. Mean body mass index was 26.73 ± 1.65 kg/m2. A second application was required in 59 (33.5%) cases. Table 1 provides a summary of the patients’ demographic data. The majority of participants had a history of vaginal delivery. Women with cesarean section as the sole mode of delivery were very limited and were not analyzed as a separate group. The majority of participants were premenopausal. The number of postmenopausal women was limited and therefore no separate subgroup analysis according to menopausal status was performed.

Table 1.

Baseline Demographic and Clinical Characteristics of the Study Population

	Vaginal Laxity
	No	Mean ± SD	Median (IQR)
Age (years)	136	38.58 ± 7.58	39 (34–44)
Height (cm)	136	167.73 ± 3.08	168 (166–170)
Weight (kg)	136	75.65 ± 5.3	75 (72–79.75)
BMI	136	26.89 ± 1.74	26.61 (25.61–28.02)
Parity	136	2.99 ± 0.95	3 (3–3)
NSD	136	2.4 ± 1.32	3 (2–3)
CS	136	0.61 ± 0.95	0 (0–1)
Degree of Laxity	136	2.46 ± 0.5	2 (2–3)
Number of Total Sessions 1	136	3.03 ± 0.17	3 (3–3)
Number of Total Sessions 2	136	0.33 ± 0.47	0 (0–1)

CS: number of previous cesarean deliveries;

NSD: number of spontaneous vaginal deliveries

Sexual Function, Urinary Symptoms, and Genital Self-Image: Time-dependent changes in FSFI, MISI, and FGSIS scores are presented in Tables 2 and 3, and are illustrated in Figs. 1, 2, and 3. One hundred seventy-six patients underwent evaluation for the first application, and 59 for a second application. In terms of comparison between preoperative and postoperative FSFI total and subscales scores, statistically significant differences were observed across all domains in favor of the postoperative stage for both the first and second applications (p < 0.001). Notably, in the preoperative phase, all FSFI scores, except for the pain domain, were significantly lower before the first application compared to before the second (p < 0.05).

Fig. 4.

Flow diagram showing patient selection, baseline data availability, and follow-up throughout the study period

Table 2.

Changes in Satisfaction Scores over Time

		Vaginal Laxity
		Initial	4–6 Weeks	1st Year	2nd Year	p
Satisfaction	Mean ± SD	2.38 ± 0.57	4.5 ± 0.62	4.18 ± 0.96	3.71 ± 1.14	0.0001‡
	Median (IQR)	2 (2–3)	5 (4–5)	5 (3–5)	4 (3–5)
Dunn’s Multiple Comparison Test		Satisfaction
Initial / 4–6 Weeks		0.0001
Initial / 1st Year		0.0001
Initial / 2nd Year		0.0001
4–6 Weeks / 1st Year		0.874
4–6 Weeks / 2nd Year		0.0001
1st Year / 2nd Year		0.0001

^‡Friedman test

Table 3.

Changes in Urinary, Sexual Function, and Genital Self-Image Scores over Time (MISI, FSFI, and FGSIS)

	Vaginal Laxity
	Initial		4–6 Weeks	1st Year	2nd Year	p
MISI	Ort ± SS	18.24 ± 3.97	1.77 ± 1.14	1.76 ± 1.38	5.47 ± 3.24	0.0001*
FSFI Desire	Ort ± SS	4.34 ± 0.48	4.55 ± 0.46	4.53 ± 0.44	4.41 ± 0.43	0.0001*
FSFI Arousal	Ort ± SS	3.83 ± 0.36	4.47 ± 0.36	4.43 ± 0.38	4.19 ± 0.39	0.0001*
FSFI Lubrication	Ort ± SS	4.31 ± 0.31	4.90 ± 0.26	4.82 ± 0.28	4.57 ± 0.32	0.0001*
FSFI Orgasm	Ort ± SS	3.72 ± 0.35	4.56 ± 0.32	4.43 ± 0.41	4.09 ± 0.41	0.0001*
FSFI Satisfaction	Ort ± SS	3.97 ± 0.38	4.65 ± 0.30	4.51 ± 0.41	4.28 ± 0.43	0.0001*
FSFI Pain	Ort ± SS	4.73 ± 0.40	5.06 ± 0.35	5.04 ± 0.35	4.80 ± 0.29	0.0001*
FSFI Total Score	Ort ± SS	24.89 ± 1.64	28.2 ± 1.48	27.76 ± 1.65	26.26 ± 2.69	0.0001*
FGSIS	Ort ± SS	15.00 ± 1.78	19.95 ± 1.13	19.76 ± 1.19	17.92 ± 2.37	0.0001*
• Paired one-way analysis of variance
Newman Keuls Multiple Comparison Test	MISI	FGSIS
Baseline / 4–6 Weeks	0.0001	0.0001
Baseline / 1st Year	0.0001	0.0001
Baseline / 2nd Year	0.0001	0.0001
4–6 Weeks / 1st Year	0.874	0.0001
4–6 Weeks / 2nd Year	0.0001	0.0001
1st Year/ 2nd Year	0.0001	0.0001
Newman Keuls Multiple Comparison Test	Desire	Arousal	Lubri	Orgasm	Satis	Pain	Total S
Baseline / 4–6 Weeks	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001
Baseline / 1st Year	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001
Baseline / 2nd Year	0.0001	0.0001	0.0001	0.0001	0.0001	0.001	0.0001
4–6 Weeks / 1st Year	0.022	0.0001	0.0001	0.0001	0.0001	0.198	0.0001
4–6 Weeks / 2nd Year	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001
1st Year / 2nd Year	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001	0.0001

Fig. 1.

Changes in MISI and FGSIS Scores over Time in Women Treated for Vaginal Laxity. *p < 0.001 compared with baseline

Fig. 2.

Changes in FSFI Domain Scores over Time following CO₂ Laser Treatment. *p < 0.001 compared with baseline

Fig. 3.

FSFI Total Score Changes over Time after Laser Treatment. *p < 0.001 compared with baseline

Postoperatively, FSFI total and arousal scores were significantly higher following the first application, while orgasm scores were significantly higher after the second (p < 0.05). Figure 2 shows the trajectory of FSFI subdomain scores across all follow-up periods. Figure 3 shows changes in FSFI total scores from baseline to the second year.

FGSIS scores improved significantly postoperatively after both laser applications (p < 0.001). Preoperatively, FGSIS scores were significantly lower before the first application than before the second (p < 0.001). Postoperatively, scores were significantly higher after the first application compared with after the second (p = 0.002). These changes are shown graphically in Fig. 1.

PGI-I scores were statistically significantly lower in the preoperative stage than in the postoperative stage for the first application. (p < 0.001). When therapeutic success was defined as PGI-I scores of 1 (‘very much better’) or 2 (‘much better’), the majority of patients met the criteria for clinical success following treatment.

MISI scores were significantly higher in the preoperative period and significantly lower in the postoperative period for both applications (p < 0.001). Before treatment, MISI scores were significantly higher before the first application than before the second (p < 0.001). After treatment, MISI scores were significantly lower after the first than after the second application (p = 0.019). MISI score trajectories are presented in Fig. 1.

VSQ scores were significantly higher preoperatively and significantly lower postoperatively for both applications (p < 0.001). Preoperative VSQ scores were significantly higher before the first application than the second (p < 0.001). Postoperatively, VSQ scores were significantly lower after the first application than after the second (p < 0.001).

Harms and Adverse Events

No serious adverse events related to fractional CO₂ laser treatment were observed during the study period. Mild and transient adverse effects, including temporary vaginal warmth, mild edema, erythema, or short-term watery discharge, were reported by a small number of patients following treatment. These symptoms resolved spontaneously within a few days and did not require additional medical treatment. No cases of infection, scarring, dyspareunia, worsening of urinary symptoms, or treatment-related discontinuation were recorded.

Discussion

With its examination of the efficacy of fractional CO2 laser application in the treatment of VL and a two-year follow-up duration, this study makes a significant contribution to the existing literature. The findings show that laser therapy resulted in significant improvement in several parameters from the first application, but that this effectiveness exhibited a partial decrease over time. However, marked improvement in symptoms was again observed with repeated applications, particularly the second session. This suggests that the long-term management of VL may require more than one session. The decreased efficacy observed at the end of two years may be attributed to the physiological decline of the collagen remodeling cycle after 12–18 months, an age-related decrease in tissue elasticity, and a decline in regenerative capacity. In addition, a history of recurrent vaginal deliveries and impaired pelvic floor muscle function may also restrict long-term durability by reducing mechanical support.

Despite VL being a frequent complaint in several age groups, there is still no consensus in the literature regarding its definition and measurement. Although VL was defined as ‘excessive vaginal looseness’ in the IUGA/ICS report [13], there is no universally recognized objective criterion for diagnosis. This diagnostic uncertainty leads to studies of VL-related sexual function impairment reporting inconsistent results. Polland et al. [14] showed no association between VL and physical examination findings or sexual function, Goodman et al.’s multi-center study [15] reported marked improvement in sexual function scores following surgery directed toward VL.

Large-scale reviews published in recent years emphasize that the existing tests used in the measurement of VL are to a large extent subjective and that there is still no objective, gold standard method [16]. Diversifying the evaluation tools used in studies is therefore important. The use of five different validated scales represents a particular strength of the present study. These discrepancies may be due to the fact that initial VL symptoms may not always lead to marked sexual function impairment, but that outcomes achieved post-treatment may enhance sexual satisfaction. The limited decrease in the orgasm subscale score in this study indicates a different response pattern compared to the marked improvement in the other FSFI subdomains. In contrast to more rapidly modifiable parameters such as arousal and lubrication, the orgasm response is dependent on much more complex biopsychosocial mechanisms including age, neurovascular integrity, psychological factors, performance anxiety, partner compatibility, and associated dynamics. The idea that the orgasm domain may not improve as markedly or quickly as other areas in patients treated using energy-based devices is also supported in the literature. Indeed, Krychman et al.’s randomized controlled study (VIVEVEI) reported only a minimum change in orgasm subscores following radiofrequency therapy [17]. Similarly, in their study using CO₂ laser, Salvatore et al. showed that the orgasm domain remained more stable compared to other subscales [18]. We therefore think that different response in orgasm scores derives from the multifactorial structure of orgasm, rather than from the biological effect of laser therapy. Although statistically significant improvements were observed across all FSFI domains, the clinical relevance of these changes is best interpreted in conjunction with patient-reported improvement. The parallel improvement in PGI-I scores supports the clinical meaningfulness of the observed FSFI changes. Importantly, although baseline FSFI total scores were below the commonly accepted cutoff for sexual dysfunction (< 26.55), post-treatment scores exceeded this threshold, supporting a clinically meaningful improvement in sexual function.

Additionally, the FSFI employed in the great majority of studies is reported to be potentially insufficiently specific for basic VL evaluation due to the division of its structure into subdomains, for which reason evaluation tools specific to the condition such as the Vaginal Laxity Questionnaire (VLQ) are needed [12]. The VLQ is frequently used to evaluate the symptoms and severity of VL. It measures perceptions of laxity/tightness by means of a Likert-type scale, and although it has not yet been validated, it appears to be sufficient for the subjective evaluation of VL symptoms and the distress associated with these [16].

Recent studies examining the relationship between sexual function and VL show that the condition is not always consistent with physical findings, but that women’s subjective perception of vaginal tightness is a determinant of sexual satisfaction [19]. This supports the idea that subjective improvements determined following laser therapy are clinically significant. In this context, the observed improvements in FSFI scores together with high patient satisfaction suggest that fractional CO₂ laser treatment may have a positive impact on symptoms associated with vaginal laxity. These findings further support the concept that patient-reported outcomes may better reflect clinically meaningful improvement than anatomical or physical examination findings alone [14].

Conventional surgical methods have been employed in the treatment of VL for many years, although limitations in terms of lengthy healing times and sexual activity have encouraged the search for less invasive methods. From that perspective, fractional CO2 laser therapy as a promising option for VL. The fact it can be performed on an outpatient basis, ease of application, and high patient comfort during the procedure make laser therapy a noteworthy method in the management of VL. Toplu et al. reported that approximately 90% of patients feel comfortable during the procedure, representing an important advantage over surgical methods [20].

A recent study investigating laxity developing following vaginal delivery reported that fractional CO2 laser produced a marked improvement in postpartum laxity and positive effects lasting up to 12 months, particularly in terms of sexual function [21]. These findings confirm the long-term benefits of repeated sessions.

Powerful evidence in the literature supports the effectiveness of laser therapy in VL. One previous study reported that fractional CO2 laser application resulted in 85% patient satisfaction in 30 women with VL, sexual function disorder, and urine leakage. Another study, evaluating 84 premenopausal women, reported that laser therapy was safe and effective in terms of sexual function and VL during six-month follow-up [22]. A randomized controlled study compared CO₂ laser and sham laser and reported significant VL score improvement in the laser group [23]. However, the 12-week follow-up period imposed a limitation in terms of the long-term effect.

A comparative study involving 47 patients and published in 2021 compared surgical and laser treatments by grouping patients on the basis of VL severity according to one-year follow-up findings. The results showed that laser represented a suitable option in addition to surgery in both mild and severe VL cases [24]. A more recent systematic review reported that energy-based devices resulted in significant short-term improvements in the treatment of VL, but that the studies involved were of low quality [8]. It concluded that further, large sample studies with long follow-up periods were of considerable importance.

In the present study, laser therapy exhibited a significant effect, independently of VL severity, in 176 patients followed-up over two-years. From that perspective, this research is one of the few studies in the literature to explore the long-term results of laser therapy. It also makes a significant contribution to the scientific literature by investigating the need for a second application and by re-evaluating the results following the second application.

The AUGS 2022 update described the current evidence as ‘insufficient’ and concluded that decisions should be made through a joint approach between the patient and physician. Studies involving large samples and long-term results are therefore important in terms of strengthening the level of evidence in guidelines [25, 26]. Considering the cautious approach adopted by AUGS 2022 and IUGA 2023, the two-year follow-up period of the present study is also valuable in terms of filling that knowledge gap.

A large sample size represented an important methodological strength since similar studies are frequently limited to small patient groups. In addition, the use of five different validated scales is another factor that enhances the reliability of the results. This is the first clinical study in the literature to systematically evaluate the effects of both first and second laser applications in a sample of 176 patients using five validated tools. However, a number of limitations also need to be considered. First, its retrospective design and the absence of a control/sham group make it difficult to differentiate the true effect of the laser from a placebo effect. There also exists the possibility of selection bias. Another limitation is the use of a subjective scale such as the VLQ due to the lack of an objective assessment tool for VL. Finally, the severity of VL was not rated using a standard classification. These limitations derive from the fact that the definition and classification of VL are both still unclear in the literature. Menopausal status and hormone replacement therapy were not analyzed as separate subgroups due to the limited number of postmenopausal participants. The retrospective design represents a limitation of the study; however, it reflects real-world clinical practice and enables evaluation of long-term outcomes in a large cohort. Prospective controlled studies are warranted to further validate these findings.

In conclusion, the current research is one of the first extensive studies to compare first and repeat laser applications using validated scales and to report two-year follow-up data. The study shows that laser therapy is an effective modality in reducing VL symptoms. While first applications provided significant improvement, the subsequent slight gradual decrease in efficacy suggests that more than one session may be required. The improvement observed after the second session shows the importance of additional sessions for permanent benefit. Booster sessions at 12 months may be recommended for selected patients. Further studies are now needed to consider the efficacy and reliability of repeat laser applications in detail.

Author Contribution

T.D. and P.K. designed the study and supervised the research process. T.D. collected the clinical data. P.K. and O.D. performed the data verification and methodological review. H.C.D. and U.K.D. conducted the statistical analysis. E.A. and A.E.K. prepared the tables and figures. T.D. and P.K. drafted the main manuscript text. All authors critically revised and approved the final version of the manuscript. All authors listed on this manuscript meet the authorship criteria defined by Springer Nature. Each author has: • made substantial contributions to the conception and design of the study, data acquisition, analysis, or interpretation; • participated in drafting the manuscript or revising it critically for important intellectual content; • approved the final version to be published; and • agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have given explicit consent for submission and confirm that the responsible institutional authorities approved the conduct of this study. Individuals who contributed to the work but do not meet authorship criteria have been appropriately acknowledged.

Funding

No external funding was received. All laser procedures were self-paid by the participants.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. It was approved by the local ethics committee (E-46059653–050.99–251446959).

Consent to participate

Informed consent was obtained from all participants.

Consent for publication

All authors gave consent for publication.

Registry and Registration No. of the study/trial (Registration number in a public trials registry) No.

Animal Studies

No.

Conflict of interest

The authors declare no competing interests.