Lichen sclerosus (LS) is an acquired, non-communicable, chronic inflammatory disease. The disease most commonly affects the anogenital region, though extragenital involvement can occur in a minority of cases. The disease predominantly affects postmenopausal women but can also manifest in men and at younger age (1). Clinically, LS is characterized by porcelain-white, atrophic plaques, often accompanied by pruritus, pain, and, in chronic cases, architectural changes and scarring of the vulva, perineum, or penis. Complications include sexual and urinary dysfunction, significant impairment in quality of life, and an increased risk of squamous cell carcinoma, particularly in the vulva and penis. The diagnosis of LS is based on characteristic clinical features and supported by histopathology where needed (epidermal atrophy, homogenization of collagen in the upper dermis, thickened basement membrane, and a band-like lymphocytic infiltrate). (1, 2).

In general, there is a well-documented inverse correlation between mental health and sexual dysfunction (3, 4). In line, some studies suggest a higher prevalence of depressive symptoms, anxiety, and reduced quality of life in patients with LS compared to controls, although most are limited by sample size, cross-sectional design, and lack matching accounting for risk factors of psychiatric disease (5). In more detail, in 765 women with LS 42% were also diagnosed with a depression as opposed to 22% of the controls, amounting to an odds ratio (OR) of 2.16 (95% confidence interval [CI] 1.82–2.57). Likewise, an increased odds of anxiety was also noted in this study (6). A Swedish population-based study investigating comorbidities associated with LS included 154,424 patients and a sex- and age-matched control group of 463,273 individuals without LS. Regarding mental health outcomes, the study documented significant associations of LS with alcohol abuse, and nicotine dependence (2). Furthermore, among women diagnosed with LS, those with vulvar involvement showed an increased risk of receiving prescriptions for antidepressants and benzodiazepines, as well as being diagnosed with depression or anxiety disorders, compared to women with LS without vulvar involvement (7). A systematic review of several smaller studies examined the prevalence of depression in patients with vulvar inflammatory dermatoses, including LS. The study reported depression prevalence estimates ranging from 14 to 50%, depending on assessment tools and study populations. However, only eight studies employed validated depression instruments, and most of the studies were cross-sectional or retrospective chart reviews assessing associations rather than incident risk. Thus, the temporal relationship between LS diagnosis and subsequent psychiatric disease was rarely addressed (8). Another limitation of these studies is reverse causation, as individuals with psychiatric disorders may have increased healthcare utilization, thereby raising the likelihood of receiving an LS diagnosis.

Overall, this underscores the need for longitudinal studies assessing the risk of psychiatric disorders following LS diagnosis. Thus, to clarify the potential impact of LS on mental health, we conducted a large-scale retrospective cohort study investigating a spectrum of psychiatric diseases. To reduce confounding, we employed propensity-score matching. To strengthen the temporal relationship, we assessed psychiatric outcomes only after the LS diagnosis.

In this large, retrospective cohort study using EHRs from over 42,000 patients diagnosed with LS, we found a significantly increased risk of being diagnosed with depressive episodes, MDD, and stress-related disorders, particularly reaction to severe stress, following LS diagnosis. These findings were robust across three sensitivity analyses and persisted in most subgroup analyses stratified by sex and self-reported ethnicity.

Our results extend upon previous insights from a small number of earlier, mostly cross-sectional studies suggesting an association between LS and psychiatric morbidity (2, 6, 8). Importantly, our study is among the first to analyze incident risk of psychiatric disorders after LS diagnosis using a temporal design, which allows for a better inference about directionality. The observed association is biologically and psychosocially plausible: LS frequently affects intimate body areas, often in a disfiguring and painful manner, contributing to sexual dysfunction, stigmatization, and psychological distress (1, 14, 15). The consistent increase in psychiatric risk across all sensitivity and most subgroup analyses suggests that mental health is an important but still underrecognized aspect of LS care.

While both female and male patients with LS showed elevated risks for depressive episodes, results for MDD were statistically robust only in females, possibly due to limited statistical power in the smaller male subgroup. Similarly, increased risk for depressive and stress-related disorders was observed in White patients, but not in Black or African American patients with LS. This might reflect genuine differences in disease perception, healthcare access, or diagnostic bias (16). However, the relatively small number of LS cases among Black or African American individuals diagnosed with LS is the most likely explanation for this finding. Notably, the HR for depressive episodes in Black or African American LS patients (HR 1.287, CI 0.96–1.724, p = 0.0903) pointed in the same direction as in White patients (HR 1.25, CI 1.157–1.349, p < 0.0001), suggesting a similar underlying effect that may have gone undetected due to limited power. Similar considerations apply to MDD and stress-related disorders, as well as for MDD and stress-related disorders in male patients with LS.

Notably, we found no evidence of increased risk for suicidal ideation, suicide attempts, or schizophrenia in patients with LS compared to controls. These findings were consistent across all sensitivity and subgroup analyses. However, low event counts limit statistical power and preclude definitive conclusions. In principle, this limitation could be addressed through a meta-analysis of existing studies. However, the literature on this topic is sparse at best: Only one study reported suicidal ideations in 6 out of 422 patients (1.4%) with vulvar LS (17). This figure is substantially higher than the 0.08% prevalence of suicidal ideation documented in our study. The apparent discrepancy likely reflects differences in study design: Prospective assessment with direct inquiry about suicidal thoughts (17) versus our retrospective cohort approach based on coded diagnoses. Thus, the prevalence of psychiatric disease is potentially underreported in LS.

Several limitations should be acknowledged. First, although propensity-score matching was used to minimize baseline imbalances, residual confounding from unmeasured variables (e.g., symptom severity, or access to mental health care) cannot be ruled out. Second, LS diagnosis was based on ICD-10-CM codes, which may vary in accuracy across healthcare providers and institutions. Third, psychiatric outcomes were also defined by diagnostic codes, which may not capture subclinical disease or undiagnosed cases. Fourth, although the temporal sequence of diagnoses can be established, the retrospective design does not permit causal inference, and residual or bidirectional confounding cannot be ruled out. Moreover, although outcomes were analyzed only after the LS diagnosis, diagnosis dates in EHRs may lag true clinical onset; therefore, our findings concern hazards of recorded diagnoses rather than definitive disease onset. Fifth, the relatively small number of male and Black or African American patients with LS limits the power of subgroup analyses and the generalizability of these findings to underrepresented populations. Sixth, in some cases, the proportional hazards assumption was violated. Yet, the chi-square and p-values calculated from the Schoenfeld residuals are sensitive to differences in time value transformations used by different software packages. For example, KM time transformations used by Survival and SAS software can yield different chi-square statistics, despite agreement in hazard ratio estimates. This discrepancy arises from the time shifts between transformed values. Thus, TriNetX advises to interpret these chi-square and p-values as qualitative guides to the degree of time variance in hazard ratios, rather than as exact quantitative metrics (9). Finally, outcome frequency for suicide-related endpoints and schizophrenia was low, precluding definite conclusions for these disorders.

In conclusion, our findings show that LS is associated with a modest but statistically and clinically relevant increase in the risk of depressive episodes, MDD, and stress-related disorders. These results underscore the need for integrated care approaches that include mental health screening and support as part of routine LS management. Future studies should explore whether targeted mental health interventions can mitigate psychiatric risk in this population.