Association between vitiligo and sexual dysfunction: current evidence

Abstract Background We discovered that vitiligo was associated with sexual dysfunction in clinical diagnosis and treatment; however, no further analysis had been performed due to a lack of data. Objective This study aimed to clarify the relationship between vitiligo and sexual dysfunction. Methods We searched six databases (PubMed, Embase, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang Data Knowledge Service Platform) for nearly 40 years. Results According to the search strategy, 91 relevant studies were retrieved, of which 4 were included in the analysis. The Arizona Sexual Experience Scale (ASEX) score (mean difference [MD] 4.96, 95% confidence interval [CI] 2.78–7.13, p < 0.00001) was higher in the vitiligo group than in the control group. The Arabic version of the Female Sexual Function Index (AVFSFI) score (mean difference [MD] − 3.40, 95% confidence interval [CI] − 5.49 to −1.31, p = 0.001) was lower in the vitiligo group than in the control group. Conclusions Patients with vitiligo were found to be at greater risk of sexual dysfunction. Moreover, the association between vitiligo and sexual dysfunction was stronger in women than in men. Key Messages Patients with vitiligo were found to be at greater risk of sexual dysfunction. The association between vitiligo and sexual dysfunction was stronger in women than in men.


Introduction
Vitiligo is a commonly acquired pigmented disease characterized by the destruction of epidermal melanocytes (MC), which results in decreased melanin production and skin depigmentation.Although vitiligo affects approximately 1% of the global population, its prevalence does not vary significantly by sex, ethnicity, or geographic region [1].Its pathogenesis has not been elucidated.However, research has shown that the etiology is closely related to genetics, autoimmune diseases, melanocyte self-destruction, trace element deficiency, environmental triggers, epidermal oxidative stress, and other factors [2][3][4][5].The commonly used methods for vitiligo treatment in modern medicine include drug therapy (oral glucocorticoids, immunomodulatory trace elements, topical glucocorticoids, and calcineurin inhibitors), phototherapy (narrow-wave ultraviolet and 308 excimer laser), and surgical treatment (surgical skin grafting and depigmentation treatment) [6].
Vitiligo is generally asymptomatic because skin lesions can cause local or systemic depigmentation, which affects the appearance and greatly impacts the normal social activities and mental health of patients [7], especially in individuals with darker skin.
The skin has a role in sexual function, and skin damage can adversely affect sexual function [8].More than 50% of patients with vitiligo experienced association problems with the opposite sex, and most felt that their sex lives had been immediately impacted [9].Several studies have shown that vitiligo has an adverse impact on sexual relationship [8,[10][11][12].A recent systematic review showed that more than a quarter of patients had sexual dysfunction [13].Some studies suggest that sexual relationship problems caused by vitiligo are more pronounced in men and single people [12], while other studies suggest that they are more pronounced in women [8].
There is currently a lack of meta-analyses on the relationship between vitiligo and sexual dysfunction; therefore, we searched all relevant clinical databases on vitiligo and sexual dysfunction and quantitatively analyzed their results.Furthermore, we analyzed the effect of sex differences on the relationship between vitiligo and sexual dysfunction.

Data sources and searches
The PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, China Science and Technology Journal Database, and Wan Fang Database were searched from inception to December 31, 2021, for literature on the relationship between vitiligo and sexual dysfunction using search keywords including vitiligo, sex relationship, sex dysfunction, and sex function.

Study selection
Publications were selected based on the following inclusion criteria for the studies: (1) human-only studies; (2) having a control group; (3) original data could be extracted; and (4) data were assessed using odds ratios (ORs), estimated confidence intervals (CIs) for hazard ratios, and hazard ratios (sufficient data could be used to calculate them), and sexual dysfunction was considered a specific outcome event.Initially, 91 articles were selected from the search (Figure 1).Then, these articles were carefully reviewed.Finally, this systematic review included four studies.A flowchart describing the screening process is shown in Figure 1.

Data extraction
The following data were collected for each included study: (i) first author, (ii) study characteristics (year, duration, country, and design), (iii) participant characteristics (mean age, number of cases and controls, disease duration time, and quality of sexual life score), and (iv) outcome features.

Quality assessment
Study quality was assessed using the Newcastle-Ottawa scale [14] (Table 1).This scale divides case-control studies into selection, comparable, and exposure categories and cohort studies into selection, comparable, and outcome categories.The selection category included four quality items, one for comparability and three for exposure.

Data synthesis and analysis
Meta-analysis was performed using RevMan 5.4 software for Mac, and 95% CIs for mean differences (MD) and risk ratios (RR) were calculated for continuous and binary variables, respectively.If there was statistical heterogeneity (p < 0.10 or I 2 -values > 50%), a fixedeffects model was used; otherwise, a random-effects model was used.The methodology and results of this study strictly followed the meta-analysis of observational studies in epidemiology group guidelines and checklist [18].

Results
Of the 91 relevant studies initially detected, 4 crosssectional studies involving 365 participants with vitiligo aged 16-60 years were included (Figure 1).The characteristics of these studies are summarized in Table 2.

Secondary Outcomes
Dermatological Life Quality Index (DLQI) Two studies [16,17] calculated the effect of vitiligo on the Dermatological Life Quality Index (DLQI) scores.

Marriage time
Two studies [16,17] demonstrated a significant influence of marriage time between patients with vitiligo and controls (MD: 4.81; 95% CI: 1.29, 8.33; p ¼ 0.007; Table 5, Figure S3).However, no significant difference was found between patients with vitiligo without genital involvement and controls using random-effects  [17] þþþ þþ þþ 7 A star system was used to perform a semiquantitative assessment of the study quality.In the selection and exposure categories, a study adjudged a maximum of 4 stars for each numbered item.A maximum of 2 stars can be assigned for comparability.NOS ranges from 0 to 9 stars.We deemed high-quality studies that achieved !7 stars, medium-quality studies 4 to 6 stars, and poor-quality studies <4 stars.

Discussion
Vitiligo is a relatively common acquired pigmented skin disease that manifests as localized or generalized complete depigmentation of the skin and mucous membrane.It is caused by the disappearance of melanocyte function in the skin; however, the mechanism is unclear.Vitiligo varies in severity; the course of the disease is unpredictable and requires lifelong therapy [21].Although vitiligo is not life-threatening or physically incapacitating, it can greatly affect a patient's mental health [9,10,22], sexual dysfunction [8,12,[15][16][17]23], and quality of life [11,16,22,23].Since the 1980s, only seven studies [8,[15][16][17][22][23][24] have investigated the possible association between vitiligo and sexual dysfunction.Some studies suggest that sexual relationship problems caused by vitiligo are more pronounced in men and single people [12], while others suggest that they are more pronounced in women [8].Therefore, a meta-analysis study is needed to further examine the correlation between vitiligo and sexual dysfunction [12].
The outcomes of our study demonstrated that patients with vitiligo were at a greater risk of developing sexual dysfunction, and the association was stronger in female patients (Table 3, Figure S1).Sexual dysfunction in female patients may be more closely related to desire, lubrication, and satisfaction (Table 4, Figure S2).This problem may be due to the patient's embarrassment, inferiority complex, and their partner's embarrassment.Vitiligo is considered a disfiguring skin disease that places a heavy social and psychological burden.Sexual dysfunction is psychosocial comorbidity in more than a quarter of the patients with vitiligo, and female patients have a higher psychosocial burden [13].
Vitiligo is known to seriously impair patients' quality of life [16,17,[25][26][27][28].Our results confirmed this: patients had higher DLQI scores, regardless of genital involvement (Table 5, Figure S3).This may be related to the implementation of DLQI scoring, which measures functional and lifestyle impairment from skin disease but not the emotional impact of the disease.
These results suggest that during the treatment of vitiligo, attention should be paid to patients' quality of life and psychosocial health, and corresponding treatment strategies should be actively provided.Three studies [29][30][31] showed that in participants without vitiligo, sufficient knowledge of the disease promoted more positive interactions with people with vitiligo than in participants without the knowledge of the disease.Our results showed that compared with controls, patients with vitiligo had longer marital durations, and  these were more pronounced in patients with genital involvement (Table 5, Figure S3).Therefore, if the knowledge of vitiligo disease is popularized among the family members and sexual partners of patients with vitiligo, along with psychological counseling, it may reduce the psychological burden of the patients themselves and improve their quality of life, sexual partners and families.This meta-analysis revealed no significant difference in educational attainment between patients with vitiligo and healthy individuals (Table 6, Figure S4).This may indicate that vitiligo and educational attainment  do not affect each other; however, further verification is needed.Although there was no significant difference in fertility between patients with vitiligo and controls, among participants, there were more patients with vitiligo with three to four children than the controls (Table 6, Figure S4).In the future, we may explore the relationship between vitiligo and fertility, given that no relevant literature has been reported.

Limitations
This study had some limitations.First, the included studies were from Asia and Africa only, as data from studies in Europe and the United States are lacking.
Second, this study was highly heterogeneous.Third, the previous systematic literature review [13] of the psychosocial effects of vitiligo, including sexual dysfunction, was qualitative, whereas this study was quantitative.Regarding the data analysis, ASEX and AVFSFI were the main judging indicators in our study, while the previous study used ASEX only [13].Our article described the relationship between vitiligo and sexual dysfunction, showing that women with vitiligo are more likely to have sexual dysfunction than men.The previous study did not describe this topic in detail [13].

Conclusions
In conclusion, patients with vitiligo are at greater risk of sexual dysfunction.The association between vitiligo and sexual dysfunction was stronger in women than in men.Physicians should be aware of this potential risk and actively intervene to reduce comorbidities.

Figure 1 .
Figure 1.Literature search and study selection.

Table 2 .
Characteristics of included studies.
AVFSFI: Arabic version of the Female Sexual Function Index; ASEX: Arizona Sexual Experience Scale; GI: genital involvement; NR: not reported.

Table 3 .
ASEX scores of the vitiligo and control groups with distinction between males and females.

Table 4 .
AVFSFI score of the vitiligo and control groups and scores of each component.

Table 5 .
DLQI score and marital duration of the vitiligo and the control groups; the vitiligo group distinguishes the presence or absence of genital involvement.

Table 6 .
Educational attainment and fertility between the vitiligo and control groups.