Genitourinary syndrome of menopause (GSM) is a chronic condition caused by hypoestrogenism and characterized by vulvovaginal dryness, irritation, burning, dyspareunia, and lower urinary tract symptoms. These manifestations often persist and worsen with time and can substantially impair quality of life and sexual function in midlife and older women (1, 2). Recent expert statements have therefore emphasized GSM as a female-specific non-communicable disease (NCD) that warrants proactive, long-term management rather than being regarded as an inevitable consequence of aging (1).

Epidemiologic data from Japan indicate that GSM-related symptoms are highly prevalent not only after menopause but also in late reproductive and perimenopausal ages. Cross-sectional surveys have reported frequent vulvovaginal symptoms, including dryness, pruritus, and dyspareunia, among Japanese women in their 20s–40s (3), and GSM-related complaints in women in their 40s–60s have been strongly associated with reduced sexual activity and sexual dysfunction (4). GSM is common and often underrecognized, and many women report persistent symptoms and unmet needs despite available therapies (1, 5). In a nationwide web-based survey of 10,000 Japanese women aged 40–90 years, approximately 45% reported at least one genital or urinary symptom compatible with GSM, and many expressed dissatisfaction with available management options and persistent psychological distress (6, 7). These findings suggest that tens of millions of Japanese women may be affected by GSM and underscore the need for effective and acceptable treatment strategies in real-world practice (3, 4, 6, 7).

According to the 2020 position statement of The North American Menopause Society (NAMS), recommended management of GSM includes nonhormonal vaginal moisturizers and lubricants as initial treatment, with low-dose vaginal estrogens, intravaginal dehydroepiandrosterone (DHEA), and oral ospemifene as subsequent options in women without contraindications (1). However, in Japan many of these evidence-based local hormonal therapies are not commercially available because of drug lag and drug loss. As a result, Japanese women with GSM often rely on over-the-counter moisturizers, lubricants, probiotics, and off-label approaches, and their satisfaction with symptom relief remains limited (7). This therapeutic gap has fueled interest in non-hormonal, device-based therapies such as vaginal and vulvar fractional carbon dioxide (CO₂) laser.

Fractional CO₂ laser is an energy-based technology that creates microscopic columns of controlled thermal injury in the epithelium and superficial stroma, thereby triggering wound-healing responses that promote collagen remodeling, neoangiogenesis, and restoration of tissue elasticity and lubrication (8). Early prospective studies suggested that vaginal fractional CO₂ laser improves vulvovaginal atrophy and GSM symptoms, particularly dryness and dyspareunia, in women who are unable or unwilling to use local estrogen therapy (9, 10). More recently, observational cohorts and clinical trials have reported short-term improvements in multiple symptom domains; however, randomized controlled trials comparing fractional CO₂ laser with sham treatment or standard hormonal therapy have yielded mixed results, and systematic reviews and meta-analyses restricted to randomized trials have concluded that the certainty of evidence is low (11–13). Professional societies have therefore adopted a cautious stance: the Royal College of Obstetricians and Gynaecologists (RCOG) has stated that vaginal laser therapy for GSM should not be routinely offered outside clinical trials (14), and editorial commentaries have raised concerns about potential harms and overuse in the absence of robust data (15).

Despite these uncertainties, use of fractional CO₂ laser for GSM has expanded in daily practice, especially in settings where access to approved local hormonal treatments is limited or where patients prefer to avoid hormones. In Japan, vaginal and vulvar laser therapy is increasingly offered as a self-pay, non-hormonal option in gynecologic clinics; however, large real-world datasets describing symptom trajectories, durability of treatment effects, objective changes in vulvar and vaginal tissue characteristics, and the influence of concomitant systemic hormone replacement therapy (HRT) are scarce. Therefore, the present study aimed to describe symptom-specific trajectories, responder rates, and safety outcomes of combined vaginal and vulvar fractional CO₂ laser therapy for GSM in a large single-center cohort. Any comparisons according to concomitant systemic HRT were planned as exploratory analyses rather than causal comparative effectiveness evaluations.

Genitourinary syndrome of menopause (GSM) is now understood as a chronic, progressive condition involving not only thinning of the vaginal epithelium but also stromal rarefaction, reduced vascularity, and altered neurosensory signaling across the genital and lower urinary tract, driven primarily by estrogen deficiency (1, 16, 17). These multilayered pathophysiologic changes help explain the wide spectrum of GSM manifestations and the variable response of different symptom domains to a given therapy. In this large real-world cohort of 826 women undergoing 2,129 sessions of fractional CO₂ laser therapy, we observed distinct symptom-specific trajectories and ultrasonographic changes in vulvar soft tissue thickness. Importantly, our data further illustrate the practical gap between guideline-recommended GSM therapies and real-world care in settings where approved local hormonal options are limited or underutilized, which has contributed to interest in device-based, nonhormonal approaches (1, 5).

One of the most striking observations was the disproportionately robust and durable improvement in dyspareunia compared with other symptoms. Dyspareunia is closely linked to deeper vaginal wall biomechanics—collagen content, elastin architecture, and distensibility—rather than superficial lubrication alone (16, 17). Fractional CO₂ laser creates controlled microablative thermal injury that stimulates wound-healing cascades, including fibroblast activation, collagen remodeling, and neovascularization in the lamina propria and subepithelial stroma, potentially leading to sustained modifications in tissue structure and mechanical properties (8). This “deeper-tissue” hypothesis provides a coherent mechanistic explanation for why dyspareunia—more than purely mucosal symptoms—showed the most durable benefit in our cohort. Systematic reviews and meta-analyses report improvements in dyspareunia and vaginal health-related outcomes after intravaginal laser, although certainty is often limited by heterogeneity and study design (11, 12, 18–20). Recent society statements and evidence syntheses emphasize that symptom improvement does not automatically equate to disease modification and that durable clinical benefit requires confirmation in well-controlled trials with standardized endpoints and longer follow-up (14, 20).

The significant increase in labia majora thickness documented in more than 80% of women in this study supports the concept of structural change beyond symptom reporting. Previous studies of vaginal laser modalities, including Er:YAG approaches, have described improved vaginal tissue parameters and symptom relief, suggesting that thermal effects can influence atrophic tissue structure (21). Our ultrasonographic findings extend “tissue change” assessment to the vulva, an anatomic domain that is clinically relevant for irritation, friction-related pain, and sexual discomfort, but is less frequently captured in laser studies focused only on the vagina. The finding that women with thinner baseline labial tissue exhibited proportionally greater thickening is biologically plausible, implying that more atrophic tissue may exhibit a larger dynamic range in response to remodeling stimuli. However, imaging changes should be interpreted cautiously: ultrasonography does not provide histologic confirmation, and future work should link objective structural measures with validated patient-reported outcomes and, where feasible, tissue-level correlates (20).

In contrast, improvements in vaginal dryness and urinary leakage, while evident in the short term, partially attenuated over time. This divergence likely reflects fundamental differences in symptom pathophysiology. Vaginal dryness depends heavily on epithelial maturation, mucosal hydration, and local secretory milieu, all of which are strongly estrogen-dependent and may regress relatively quickly when hypoestrogenism persists (1, 16). Urinary leakage is multifactorial (urethral sphincter function, pelvic floor support, and bladder dynamics), and may be less amenable to an intervention primarily targeting vaginal/vulvar mucosa and adjacent stroma. Consistent with this, sham-controlled trials and RCT-focused meta-analyses have reported mixed or modest effects, particularly for urinary outcomes, and have highlighted limitations in certainty (12, 13, 19, 20). Our symptom-specific “decay” pattern (durable dyspareunia improvement with partial attenuation of dryness/urinary leakage) is therefore clinically plausible and aligns with the broader evidence base that different GSM domains may require different maintenance strategies or combination therapy (1, 20).

Beyond mean changes, responder analysis and exposure–response (“dose–response”) patterns can strengthen the clinical interpretability of device-based interventions by translating statistical change into patient-relevant benefit. In pain-related and symptom-intensity outcomes measured on 0–10 scales, a ∼2-point improvement is commonly used as a clinically meaningful threshold, and responder reporting is recommended to complement mean change, especially when placebo/sham responses are substantial (22, 23). In sham-controlled trials of vaginal laser for GSM, between-group differences may be modest despite within-group improvement, highlighting the value of presenting the proportion of patients who achieve meaningful relief and identifying which domains are most likely to respond (12, 13, 20). In our cohort, symptom-specific responder rates and the graded increase in responder frequency with higher numbers of sessions (most pronounced for dyspareunia, and more moderate for dryness and urinary leakage) are consistent with multi-session paradigms used in early prospective studies and larger cohorts, where repeated treatments are intended to reinforce remodeling and symptom control (9, 10). Taken together, these results support a pragmatic implication for real-world counseling and service design: treatment benefit is heterogeneous across symptom domains, and both the probability of response and the need for additional sessions may differ by symptom phenotype—an “analysis → implication” bridge that should be prospectively tested using prespecified responder endpoints and maintenance schedules (20, 24).

A practical implication of these symptom-specific trajectories is the likely need for maintenance therapy. GSM is chronic and typically requires ongoing management; guideline documents emphasize long-term approaches and reassessment rather than one-time interventions (1). In our cohort, the attenuation of dryness and urinary leakage over ∼1 year supports counseling patients that (i) benefits may vary by symptom domain and (ii) repeated sessions or adjunctive therapies may be needed to sustain improvements in mucosa-dependent or multifactorial urinary symptoms. Defining optimal maintenance intervals remains an evidence gap and should be a priority for prospective studies that prespecify maintenance schedules and compare them with standard-of-care therapies (20).

Safety remains central in discussions of energy-based devices for GSM. Professional society statements have recommended caution and have advised that vaginal laser should not be routinely offered outside clinical trials in many settings (14). Regulatory communications have also highlighted potential risks when energy-based devices are marketed for “vaginal rejuvenation” indications without robust evidence (25). In our cohort, no serious adverse events were observed across more than 2,000 sessions, and dissatisfaction was largely associated with intercurrent conditions rather than apparent procedure-related complications. These findings are reassuring for procedural safety in an experienced clinic using standardized protocols and careful pre-treatment evaluation; however, absence of observed serious events in a retrospective cohort does not substitute for long-term, systematically ascertained safety outcomes (20).

This study has several strengths. It is one of the largest single-center cohorts of women treated with fractional CO₂ vaginal and vulvar laser therapy, providing real-world data across a wide age range. We combined symptom VAS measures with ultrasonographic assessments of vulvar soft-tissue thickness, providing convergent descriptive data on patient-reported symptom trajectories and imaging changes. However, several limitations must be acknowledged. The retrospective observational design precludes causal inference and is susceptible to selection and information bias. There was no sham-treated or non-laser control group, and follow-up was incomplete and not uniform. Symptom assessment relied on VAS scoring rather than fully validated GSM instruments, and objective measures lacked histologic confirmation. Additionally, because this was real-world practice, concomitant treatments and care-seeking behavior may have varied over time, which can influence both responder classification and apparent dose–response patterns. These issues should be addressed prospectively (1, 20).

Despite these limitations, our findings provide descriptive real-world data on symptom trajectories and ultrasonographic changes in a large Japanese cohort. Given the lack of a control/sham group and incomplete follow-up, the results should be considered hypothesis-generating rather than confirmatory evidence of effectiveness (14, 20, 26).