Testosterone Deficiency and Sleep Deprivation as Risk Factors for Psoriasis: Insights From the National Health and Nutrition Examination Survey (NHANES) 2011–2014

Introduction

Psoriasis is a chronic, immune-mediated inflammatory skin disorder that affects approximately 2–3% of the global population, with notable geographic, ethnic, and socioeconomic variations in prevalence.^1,2 The prevalence of psoriasis is higher in developed countries, particularly in regions with colder climates, such as Northern Europe, where rates can reach up to 11.8% in some populations.^3,4 In contrast, lower prevalence rates are reported in East Asia and sub-Saharan Africa.⁵ Psoriasis can occur at any age, but it most commonly manifests in adulthood, with peaks between the ages of 15–25 and 50–60.⁶ The condition is not only physically burdensome due to its symptomatic nature but also linked to significant psychological distress and reduced quality of life, as patients often experience stigma and discrimination.^7,8

In addition to skin involvement, psoriasis is increasingly recognized as a systemic disease with associations to various comorbidities, such as cardiovascular disease, metabolic syndrome, diabetes, and psoriatic arthritis.^9,10 The complex pathogenesis of psoriasis involves a dynamic interaction of genetic susceptibility and environmental triggers, such as infections, stress, obesity, and lifestyle factors.^11–13 Central to the disease’s pathophysiology is the dysregulation of the immune system, particularly the overactivation of T-cells and the production of pro-inflammatory cytokines like TNF-α, IL-17, and IL-23.^14,15 These molecular pathways not only drive the hyperproliferation of keratinocytes but also foster a pro-inflammatory state that underpins the systemic nature of the disease.¹⁶

Despite substantial advancements in understanding the immune mechanisms involved in psoriasis, much remains to be explored regarding the role of systemic factors such as hormonal imbalances and lifestyle behaviors, including sleep patterns, in modulating disease risk and severity.^17,18 Understanding these factors is crucial, as psoriasis is associated with long-term health complications, and identifying modifiable risk factors can have a significant impact on prevention and management.^19,20

In recent years, there has been growing interest in understanding how systemic factors, such as hormonal regulation and sleep behaviors, influence the onset and progression of psoriasis.^21,22 Testosterone, a key androgen hormone, plays a pivotal role in regulating various physiological processes, including immune response and inflammation.²³ Low testosterone levels, commonly observed in aging males and individuals with metabolic disorders, have been linked to increased susceptibility to several inflammatory and autoimmune diseases.^24,25 In the context of psoriasis, testosterone’s immunomodulatory properties are believed to influence disease activity by altering cytokine profiles, reducing the body’s ability to control inflammatory cascades.^26,27 However, population-based studies specifically examining the relationship between testosterone levels and psoriasis are sparse, leaving a significant gap in our understanding of this potential association.²⁸

Simultaneously, sleep has emerged as a critical factor in maintaining immune function and overall health.²⁹ Sleep deprivation and poor sleep quality are well-established risk factors for systemic inflammation and chronic diseases, including metabolic syndrome, cardiovascular disease, and mood disorders.³⁰ In particular, insufficient sleep has been associated with increased levels of pro-inflammatory cytokines, similar to those involved in psoriasis pathogenesis.³¹ Despite the potential implications of disrupted sleep patterns on skin health, few studies have explored the direct relationship between sleep duration and psoriasis, especially in large-scale epidemiological datasets.^32,33

Given the significant overlap between the pro-inflammatory states driven by both hormonal imbalance and sleep disturbances, the combined effects of low testosterone and inadequate sleep on psoriasis risk warrant further investigation.³⁴ Using data from the 2011–2014 NHANES cohort, this study aims to provide novel insights into the role of these modifiable factors in psoriasis development. By assessing testosterone levels and self-reported sleep duration in a nationally representative population, we seek to clarify the independent and interactive contributions of these factors to psoriasis risk.³⁵ The findings from this study have the potential to inform prevention strategies and clinical management of psoriasis, particularly for patients with hormonal or sleep-related issues.³⁶

Methods

Study Design

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014. A total of 19,312 participants were initially included in the survey. After excluding individuals with missing psoriasis data, 12,625 participants remained. Further exclusions were made for those missing data on testosterone levels and sleep duration, leaving 11,244 participants. Finally, after excluding women and participants missing covariate information, the study cohort consisted of 4,060 male participants, comprising 3,880 controls and 180 psoriasis cases (Figure 1).

Figure 1 Flow chart of participant selection.Note:Bold sample sizes (n=5,880; n=180) represent the final analytical cohorts included in the study.

Psoriasis

Psoriasis status was self-reported by participants in response to the question: “Have you ever been told by a doctor or other health professional that you have psoriasis?” Participants who answered “yes” were classified as having psoriasis. Psoriasis prevalence was determined based on this self-reported information, which has been used in previous NHANES-based studies to evaluate psoriasis in population-level datasets.³⁷ Due to data limitations, psoriatic arthritis cases were not excluded.

Testosterone

Total serum testosterone levels were measured using isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) following standardized NHANES procedures. Testosterone levels were categorized as low if the value was below 300 ng/dL, a commonly accepted clinical threshold for hypogonadism.³⁸ This cutoff was used to classify participants into normal and low testosterone groups for subsequent analyses.

Sleep Duration

Sleep duration was assessed through the NHANES sleep questionnaire, where participants reported their average sleep duration over the past month. Sleep duration was assessed via self-report to the question, “How much sleep do you usually get on weekdays or workdays?” Responses were categorized as < 7 (insufficient sleep) or ≥7 hours (normal sleep), in line with guidelines from the American Academy of Sleep Medicine.³⁹ Sleep duration was analyzed as both a continuous and categorical variable in the statistical models.

Covariates

In our analysis, several covariates were included to control for potential confounding factors that might influence both testosterone levels and psoriasis risk. Age was treated as a continuous variable, given its well-established association with both testosterone levels and psoriasis prevalence. Race/ethnicity was categorized into five groups (Mexican American, Other Hispanic, Non-Hispanic Black, Non-Hispanic White, and Other races) to account for known variations in health outcomes across different racial and ethnic backgrounds. Socioeconomic factors were also considered, including education (categorized into five levels from less than 9th grade to college graduate or above) and poverty-income ratio (PIR, categorized into ≤1, 1–3, and >3), both of which are linked to access to healthcare and overall health status. Marital status was included as it can affect both psychological well-being and health behaviors, with categories such as married, widowed, divorced, separated, never married, and living with a partner. Lifestyle factors, such as smoking (current smoker or non-smoker) and alcohol use (current user or non-user), were also included given their impact on inflammation, hormone levels, and overall health. Additionally, comorbidities like hypertension, hyperlipidemia, and diabetes were treated as binary variables (yes/no) since they are commonly associated with both low testosterone and psoriasis. Finally, body mass index (BMI) was categorized into three groups (<25, 25–30, and ≥30) based on its well-established role as a risk factor for both testosterone deficiency and psoriasis, as well as its significant interaction with sleep duration.⁴⁰ These covariates were included in all adjusted models to ensure a comprehensive analysis and to mitigate potential confounding effects.

Statistical Analysis

Descriptive statistics were used to summarize the baseline characteristics of the study participants, with continuous variables reported as mean ± standard deviation (SD) and categorical variables presented as frequencies and percentages. For comparisons between the psoriasis and control groups, independent t-tests were performed for continuous variables, while chi-square tests were used for categorical variables to assess statistical significance. A P-value of <0.05 was considered statistically significant.

To examine the association between testosterone levels, sleep duration, and psoriasis, multivariable logistic regression models were employed. Three models were constructed: Model 1 was unadjusted, serving as a crude comparison; Model 2 was adjusted for key demographic variables, including age and race; and Model 3 was further adjusted for a range of potential confounders, including education level, marital status, poverty-income ratio, smoking status, alcohol use, hypertension, hyperlipidemia, diabetes, and body mass index (BMI). The inclusion of these covariates aimed to control for confounding factors that may influence both testosterone levels and psoriasis risk, ensuring more accurate estimates of the association.

To explore potential non-linear relationships between testosterone, sleep duration, and psoriasis risk, restricted cubic spline (RCS) regression models were used. This allowed for a more flexible modeling approach to assess dose-response relationships and potential threshold effects. The results of the spline models were presented graphically to illustrate the shape of these associations.Subgroup analyses were conducted to explore the modifying effects of key covariates, including age, BMI, and smoking status. Interaction terms were added to the logistic regression models to assess whether these covariates altered the association between testosterone, sleep duration, and psoriasis risk. Sensitivity analyses were also performed by excluding participants with testosterone levels greater than 1000 ng/dL to evaluate the robustness of the results.

All statistical analyses were conducted using SPSS version 27.0 and R version 4.4.1. A two-tailed P-value of <0.05 was considered statistically significant for all analyses.

Results

Characteristics of the Participants

A total of 4,060 male participants were included in the final analysis, after excluding individuals with missing data on psoriasis, testosterone, sleep duration, and relevant covariates. Among them, 180 participants (4.4%) reported having a physician-diagnosed psoriasis, while the remaining 3,880 participants (95.6%) served as the control group. The mean age of participants was 48.65±17.74 years, with the psoriasis group being significantly older than the control group (53.69±16.71 vs 48.42±17.76 years, P=0.038). No significant differences were observed in the distribution of race/ethnicity, educational attainment, marital status, or smoking and alcohol consumption habits between the two groups. Notably, the psoriasis group had a higher prevalence of diabetes (P=0.029), although the prevalence of other comorbidities such as hypertension and hyperlipidemia was not significantly different. This baseline demographic and clinical profile highlights that psoriasis in this cohort may be associated with certain age-related or metabolic risk factors (Table 1).

Table 1 Baseline Characteristics of the Study Participants

Associations Between Testosterone, Sleep Duration, and Psoriasis

In multivariable logistic regression analyses, both low testosterone levels and short sleep duration were significantly associated with an increased risk of psoriasis. As shown in Table 2, in the unadjusted model (Model 1), participants with testosterone levels below 300 ng/dL had an odds ratio (OR) of 3.18 (95% CI: 2.35–4.30, P<0.001) for psoriasis compared to those with normal testosterone levels. After adjusting for age and race (Model 2), this association remained significant (OR=2.99, 95% CI: 2.20–4.05, P<0.001). In the fully adjusted model (Model 3), which controlled for a comprehensive set of covariates including education, marital status, poverty-income ratio, smoking status, alcohol use, hypertension, hyperlipidemia, diabetes, and BMI, the association between low testosterone and psoriasis persisted with an OR of 2.97 (95% CI: 2.16–4.09, P<0.001). Similarly, short sleep duration (<7 hours per night) was independently associated with an increased risk of psoriasis, with an OR of 1.76 (95% CI: 1.33–2.35, P<0.001) in the fully adjusted model. These results suggest that both hormonal imbalances and inadequate sleep may contribute to the onset of psoriasis, potentially via pathways involving immune dysregulation and systemic inflammation.

Table 2 Weighted logistic Regression Analyses of Association Between Psoriasis and Testosterone and Sleep Duration

Non-Linear Associations Between Testosterone, Sleep Duration, and Psoriasis Risk: RCS Analysis

To further investigate the potential non-linear relationships between testosterone levels, sleep duration, and psoriasis risk, restricted cubic spline (RCS) regression models were applied. The RCS analysis for testosterone (Figure 2) revealed a steep increase in psoriasis risk as testosterone levels dropped below 300 ng/dL. The risk plateaued at lower testosterone levels, indicating that extremely low levels of testosterone might not provide additional risk beyond a certain threshold. Interestingly, testosterone levels above 700 ng/dL did not appear to offer any protective effect against psoriasis, suggesting a potential ceiling effect in the relationship between testosterone and psoriasis risk.

Figure 2 Weighted restricted cubic splines plot showing the relationship between testosterone levels and the odds ratio (OR) with 95% confidence interval (CI). A reference line is included at testosterone = 388. P total < 0.0001; P for nonlinear = 0.0017.

In the case of sleep duration, the RCS analysis (Figure 3) indicated a strong non-linear association between sleep duration and psoriasis. Participants who reported sleeping less than 7 hours per night had a substantially higher risk of psoriasis, with a steep increase in risk observed as sleep duration decreased. Conversely, sleep durations longer than 8 hours showed diminishing returns, with little additional risk reduction beyond 8 hours of sleep. These findings highlight the importance of both sufficient sleep and balanced hormonal levels in mitigating psoriasis risk.

Figure 3 Weighted restricted cubic splines plot depicting the relationship between sleep duration and odds ratio (OR) with 95% confidence interval (CI). Reference lines are included at sleep duration = 7.0 and 8.7. P total < 0.0001; P for nonlinear = 0.0063.

Impact of Testosterone and Sleep Duration on Psoriasis Risk: Subgroup and Interaction Analyses

Subgroup analyses were conducted to examine the consistency of the associations between testosterone, sleep duration, and psoriasis across different demographic and clinical strata. The associations between low testosterone levels and psoriasis risk were generally consistent across subgroups defined by age, BMI, and smoking status (Figure 4). However, significant interactions were observed in certain subgroups. For example, the association between low testosterone levels and psoriasis was stronger in participants aged 50 years or older (P for interaction = 0.023), suggesting that age may amplify the effect of hormonal imbalances on psoriasis risk. Similarly, the association between short sleep duration and psoriasis was more pronounced in participants with higher BMI (P for interaction = 0.032), indicating that obesity may exacerbate the effects of sleep disturbances on psoriasis development. No significant interactions were found for smoking status. These interaction effects suggest that older adults and individuals with obesity may represent high-risk populations where hormonal imbalances and sleep disturbances are particularly impactful in driving psoriasis risk.

Figure 4 Verification of the association between testosterone, sleep duration and psoriasis by subgroup analyses and interaction analyses.Note:Bold column headers denote variable categories. Bold P values indicate statistical significance (P < 0.05). Bold interaction P values highlight significant subgroup effect modifiers. n represents the number of participants in each subgroup.

Sensitivity Analysis: Testing the Robustness of Findings After Excluding High Testosterone Levels

To test the robustness of the observed associations, a sensitivity analysis was conducted by excluding participants with testosterone levels greater than 1000 ng/dL, which represent potential outliers or individuals with abnormally high testosterone levels. As shown in Table 3, the results of the sensitivity analysis were consistent with the main analysis. Even after excluding these participants, low testosterone levels remained significantly associated with an increased risk of psoriasis (OR=2.98, 95% CI: 2.18–4.09, P<0.001), as did short sleep duration (OR=2.10, 95% CI: 1.54–2.86, P<0.001). The sensitivity analysis confirmed that the associations observed in the primary analysis were not driven by extreme values of testosterone, reinforcing the robustness and generalizability of the findings. These results suggest that even within a more conservative range of testosterone levels, the associations between low testosterone, inadequate sleep, and psoriasis remain significant and clinically relevant.

Table 3 Sensitivity Analysis of the Association Between Psoriasis, Testosterone, and Sleep Duration After Excluding Participants with Testosterone Levels >1000 ng/dL

Discussion

In this study, we investigated the association between testosterone levels, sleep duration, and psoriasis risk in a nationally representative cohort from the NHANES dataset (2011–2014). Our findings indicate that low testosterone levels and insufficient sleep are both significantly associated with an increased risk of psoriasis. These results align with existing literature on hormonal imbalances, sleep disturbances, and psoriasis, while also providing new insights into the combined effects of these factors in a large, diverse population.

Our findings on the association between low testosterone levels and increased psoriasis risk are consistent with previous studies that have explored the role of hormonal factors in autoimmune diseases.^41,42 Testosterone is known for its immunomodulatory effects, and previous research has indicated that lower testosterone levels may contribute to an inflammatory environment that exacerbates psoriasis.⁴³ For example, a study by Guarneri et al found that male psoriasis patients had lower serum testosterone levels compared to healthy controls,⁴⁴ a finding that resonates with our results. Similarly, research by Eltaweel et al demonstrated that testosterone replacement therapy in men with hypogonadism could improve psoriasis symptoms, further suggesting a protective role of testosterone.⁴⁵

The association between sleep duration and psoriasis risk observed in our study is also supported by previous research that highlights the role of sleep in immune function and chronic inflammation.^46,47 Studies have shown that insufficient sleep is associated with elevated levels of pro-inflammatory cytokines, which play a key role in psoriasis pathogenesis.⁴⁸ A recent cohort study by Gupta et al found that individuals with shorter sleep durations had a higher risk of developing psoriasis, similar to our findings.⁴⁹ Collectively, these studies emphasize the importance of both hormonal balance and adequate sleep in managing psoriasis risk.

Testosterone’s role in modulating immune responses may provide insight into its relationship with psoriasis. Testosterone acts on various immune cells, including T-cells, macrophages, and dendritic cells, to regulate the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23), all of which are critical in psoriasis pathogenesis.^50,51 Low testosterone levels are associated with an overactivation of the Th17 pathway, leading to excessive production of IL-17 and IL-23, which are key drivers of the chronic inflammation observed in psoriasis.^52,53 Furthermore, testosterone deficiency has been linked to altered skin barrier function, making the skin more susceptible to environmental triggers that can initiate or exacerbate psoriasis.^54,55

Sleep deprivation exacerbates this inflammatory state by disrupting the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased cortisol production and systemic inflammation.⁵⁶ Sleep disturbances can also impair the body’s ability to regulate immune responses, further amplifying the pro-inflammatory environment that contributes to psoriasis.^57,58 Our study contributes to the growing body of evidence suggesting that hormonal dysregulation and sleep deprivation may act synergistically to promote psoriatic inflammation.^45,59

One of the key strengths of our study is the use of a large, nationally representative sample from NHANES, which enhances the generalizability of our findings. The diversity of the NHANES cohort allows us to examine the association between testosterone, sleep, and psoriasis across different racial, ethnic, and socioeconomic groups.⁶⁰ Additionally, our use of restricted cubic spline (RCS) regression analysis enabled us to explore non-linear relationships between testosterone levels, sleep duration, and psoriasis risk, offering a more nuanced understanding of these associations.⁶¹

Another strength lies in the comprehensive adjustment for potential confounders, including age, race, BMI, education, smoking status, and comorbid conditions such as hypertension and diabetes. By controlling for these variables, we were able to more accurately estimate the independent effects of testosterone and sleep on psoriasis risk.^62,63

Despite these strengths, there are several limitations to our study that warrant consideration. First, the cross-sectional nature of NHANES data limits our ability to establish causal relationships between testosterone, sleep duration, and psoriasis. Longitudinal studies would be necessary to confirm the directionality of these associations.⁶⁴ Second, the reliance on self-reported data for psoriasis diagnosis and sleep duration may introduce recall bias, potentially leading to misclassification of psoriasis status or inaccurate reporting of sleep habits.^65,66

Additionally, while our study adjusted for a wide range of covariates, residual confounding cannot be completely ruled out. Factors such as stress levels, dietary habits, and physical activity, which may influence both testosterone levels and psoriasis risk, were not accounted for in our analysis.⁶⁷ Lastly, the exclusion of women from our analysis means that our findings may not be generalizable to female populations, where hormonal dynamics differ significantly from men.⁶⁸

Our findings highlight the need for future research to explore the interplay between hormonal regulation, sleep, and immune function in psoriasis. Longitudinal studies could help clarify the causal pathways linking testosterone and sleep to psoriasis risk. Additionally, investigating the effects of testosterone replacement therapy and sleep interventions in psoriasis patients could provide valuable insights into potential therapeutic strategies.⁶⁹ Finally, exploring sex differences in these associations may offer a more comprehensive understanding of how hormonal and lifestyle factors contribute to psoriasis risk in both men and women.

However, self-reported psoriasis and sleep data may introduce recall bias, although NHANES protocols mitigate this limitation through standardized questionnaires.

Conclusion

In conclusion, our study demonstrates that low testosterone levels and insufficient sleep are independently associated with an increased risk of psoriasis in a large, diverse population.These findings highlight the potential for targeted interventions, such as testosterone replacement in hypogonadal males and sleep hygiene programs, to mitigate psoriasis risk. Longitudinal studies are warranted to confirm causality and explore sex-specific mechanisms.