Hypothalamic-pituitary-adrenal axis, hair, and sebum: Stress-mediated dermatologic disasters of the pandemic era

Occupational stress in the pandemic era

The pandemic’s impact on occupational stress was uneven. Frontline and essential workers faced especially high pressures, while many remote-capable professionals saw fewer infection-related stressors. For example, frontline healthcare staff reported markedly elevated anxiety and depression (about 31–41%),^[8] and surveys found that educators often had even higher stress (teachers showed significantly more anxiety symptoms than other professions).^[9] Other essential workers similarly experienced increased exposure risk and job strains. In contrast, many professionals who shifted to remote work did not show worse mental health outcomes – one multi-country survey found that remote workers were no more likely to suffer mental disorder symptoms than on-site workers.^[10] The pandemic also caused a significant economic collapse (through lockdowns and unemployment), which increased stress. COVID-related unemployment affected around four out of every five workers worldwide, and studies have linked financial uncertainty to an increase in depression, anxiety, and substance abuse.^[11]

With an emphasis on the HPA axis and its dermatological ramifications during the COVID-19 pandemic, this review attempts to combine the most recent data on the neuroendocrine regulation of stress-related skin and hair problems.

Search strategy and data synthesis

A comprehensive literature search was performed across major databases such as PubMed, Scopus, and Google Scholar. These databases were selected for their comprehensive coverage of peer-reviewed biomedical literature and relevance to dermatological and psychoneuroendocrine research. Search terms were combined using Boolean operators and phrase searching (e.g., “psychoneuroimmunology AND skin” “maskne OR telogen effluvium AND COVID-19”).

Inclusion criteria

• English-language peer-reviewed publications from 2015 to 2025

• Studies aimed at skin disorders associated with stress, HPA axis dysregulation, or psychoneuroimmunological processes were considered

• Both review articles and original research with clinically validated dermatologic diagnoses.

Exclusion criteria

• Research papers that do not focus on dermatological topics were excluded

• Studies involving surgical interventions or unrelated medical devices.

Study selection

The study selection was divided into multiple stages. First, paper titles and abstracts were reviewed for inclusion and exclusion criteria. Following this, full-text articles were reviewed, and those meeting the criteria were analyzed using thematic synthesis to compare recurring patterns and themes within studies. The topics were identified and grouped depending on their patterns across different studies, separating the COVID-19 stress-related hair loss studies from maskne or other facial dermatomes. To determine the main conclusions and areas that need more research, the data analysis was then further condensed.

Data extraction and analysis

The following information was taken from every study to identify pertinent trends, procedures, and gaps in the literature:

1. Study design

2. Population/sample characteristics

3. Dermatologic outcomes related to stress or the HPA axis activity

4. Underlying mechanisms (e.g., HPA axis, neuropeptides)

5. Management strategies and future directions.

Synthesis of findings

The included studies were then synthesized to identify consistent patterns and relationships between stress, neuroendocrine activity, and dermatologic manifestations, with particular focus on the role of the HPA axis and psychoneuroimmunological mechanisms.

HPA axis and skin: The stress-dermatological link

The body responds to stress through an intricate axis consisting of the hypothalamus, pituitary gland, and adrenal glands. When stressors are present, the hypothalamus releases corticotropin-releasing hormone (CRH), which causes the anterior pituitary to release adrenocorticotropic hormone (ACTH). This triggers the adrenal cortex to release cortisol. Skin cells also express a local HPA-like circuit: epidermal keratinocytes (and melanocytes) can produce CRH, ACTH, and cortisol under stress.^[12] Figure 1 depicts the similarities and distinctions between the central HPA axis and its cutaneous counterpart.

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Figure 1:

Central versus cutaneous hypothalamic-pituitary-adrenal (HPA) axis in stress response. Flowcharts comparing the peripheral (cutaneous) and central HPA axis. While the cutaneous counterpart permits local, skin-specific stress modulation through keratinocytes, mast cells, and sebocytes, the central route promotes systemic stress responses.

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The amygdala becomes more active under stressful situations, producing CRH signals that cause the anterior pituitary gland to produce ACTH.^[13] Elevated cortisol impairs skin integrity and promotes sebum overproduction through CRH receptors on sebocytes, contributing to skin fragility.^[14,15] Sebocytes secrete sebum through hair follicles onto the skin surface.^[16] In response to prolonged stress, cortisol resistance diminishes its capability to suppress inflammatory mediators such as interleukin (IL)-1 beta.^[17] Elevated glucocorticoids reduce ceramide synthesis, impairing the skin barrier and increasing trans epidermal water loss, leading to dryness, itching, and irritation.^[13]

Three distinct epidermal cell categories that are crucial for the immunological response are melanocytes, keratinocytes, and mast cells.^[18] In response to negative triggers, the defense system produces pro-inflammatory chemicals, which in turn cause more cortisol to be produced by the HPA system. Using its anti-inflammatory qualities, cortisol reduces inflammation.^[19]

Beyond the epidermis, stress also disrupts hair follicle cycling. The anagen, catagen, telogen, and exogen stages make up the hair cycle. Stress promotes the shift from anagen to telogen and is linked to TE.^[20] By altering follicular activity, excessive concentrations of cortisol are thought to drastically change the hair development cycle.^[21]

Pandemic-related hair disorders

Pandemic triggers for hair loss

A recent study found that stress was the primary self-identified trigger for hair shedding during COVID-19 among 1,382 medical aspirants around the globe, with a greater duration and a negative impact on confidence.^[25] The hallmark of Telogen effluvium (TE) is generalized hair loss that occurs months after a major systemic stress due to an early follicular shift from the stage of anagen to the telogen stage. During COVID-19, dermatologists have observed a sharp rise in TE cases. Hypoxia, oxidative stress, systemic inflammation, and psychological stress are all potential causes.^[21,26] Elevated IL-6 caused local inflammation, catagen shift, and immunological breakdown in follicles.^[27] Onset occurred around 56.5 days post-COVID-19.^[28] The chronological link between pandemic-related stressors and the development of TE is depicted in Figure 2.

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Figure 2:

Stress-induced cytokine cascade leading to telogen effluvium. A schematic illustration of the pathophysiological chain reaction brought on by stress from a pandemic. Pro-inflammatory cytokines like interleukin-6 are increased by elevated corticotropin-releasing hormone and substance P. This disrupts the hair cycle and causes telogen effluvium approximately 56.5 days after the initial stress exposure or coronavirus disease-19 infection.

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Stress, sebum, and acne: Pathway to maskne

The skin responds to psychological stress by activating the peripheral CRH-proopiomelanocortin- ACTHcorticosteroid axis.^[33] Similar to the central HPA axis, the peripheral axis pathway is triggered by fibroblasts and melanocytes secreting CRH, which binds to CRH-R1 receptors to initiate a cascade through melanocortin receptors and stimulates the release of cortisol. ACTH suppresses immunological responses, further promoting this release. Keratinocytes also express ACTH receptors and synthesize cortisol through 11β-hydroxysteroid dehydrogenase type 1 enzyme, enhancing sebaceous activity.^[34] Acne caused by mechanical stress is worsened by masks due to humidity, heat, and friction.^[35] The mask’s CO₂ retention leads to follicle blockage, keratinocyte swelling, and pore occlusion, altering sebum composition and promoting bacterial overgrowth and inflammation.^[36] A study by Tunçer Vural (2022) showed that acne severity is proportional to prolonged mask usage, uninterrupted wear time, and minimal replacement.^[37] Facial masks can mimic tropical temperatures by creating a hot-humid microclimate, thus increasing sebum secretion by approximately 10% per 1°C.^[35,38]

Perera et al. (2022) found that mask use was associated with 51.4% of participants’ new development or worsening of acne in their facial dermatomes among 152 clinical year medical students in Georgia.^[39] Increased skin humidity, sebum production, and skin pH, along with transepidermal water loss, are among the many factors that contribute to maskne. The cheeks (65.8%) and chin (44.3%) were primarily affected, corresponding to the O-zone, which is in direct contact with the mask.^[39] Recent studies also report that approximately 71.7% (132 out of 184) of SD patients noted disease flares.^[40]

Heat, moisture, and pH changes favor Cutibacterium acnes proliferation in cutaneous dysbiosis.^[1] Sebum is utilized for growth by this bacterium and stimulates lipid synthesis.^[41] Inflammation is triggered when its porphyrins oxidize squalene. An innate immune activation and inflammatory cytokines are induced by a selection of phylotype IA1, which in turn was favored by dysbiosis on the skin.^[42,43] Thus, stress-induced hormonal changes along with environmental factors create a micro-environment that promotes the development of maskne.

Combined dermatological manifestations

The prevalence of combined hair and sebaceous disorders has risen during the COVID-19 pandemic, primarily linked to psychological stress and viral immune disruption. A case of a 15-year-old girl with self-inflicted lesions during the pandemic showed complete relief after psychodermatological care was provided to her. The hybrid multidisciplinary consultation allowed identifying the emotional origin as the skin lesion developed and was exacerbated as a result of school bullying and family stress.^[44]

Surveys during the COVID-19 outbreak among 460 patients found skin-picking or TTM in over 67%.^[45] A questionnaire-based study showed TE occurred in 27.9% of the 563 participants.^[46] These surveys reveal the psychodermatologic cycle where visible scalp disorders worsen psychiatric conditions and vice versa. Pandemic-related stress, as well as the usage of masks for long periods, can aggravate conditions such as SD and scalp psoriasis.^[47,48]

A shared psychopathic trigger and hormonal vulnerability are indicated in many cases of TE coexisting with androgenetic alopecia, particularly shown in women. Post-vaccination also alopecia and SD flares were noted as stress and immune mechanisms act as mediators.^[49] A 100% psychological impact was reported in adolescent psychoderm settings from skin conditions, along with lower self-esteem noted in 85% during the pandemic.^[44] Altogether, psychosomatic combined manifestations necessitate multidisciplinary, model-based care to address both emotional triggers and cutaneous manifestations. The prevalence of key pandemic-related dermatologic conditions reported in recent studies is presented in Figure 3.

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Figure 3:

Prevalence of pandemic-related dermatologic conditions. Distribution of common dermatologic conditions observed during the coronavirus disease-19 pandemic. Seborrheic dermatitis flares and trichotillomania were the most reported, followed by maskne and then telogen effluvium.

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Table 1 offers a comparative overview of the main stress-related dermatological diseases seen during the COVID-19 pandemic, along with information on their causes, symptoms, and diagnostic methods.

Interpretation of findings

The HPA axis controls cortisol, which affects the hair follicle cycle and skin inflammation. Patients with androgenic alopecia have been found to have elevated levels of cortisol as well as CRH, ACTH, and SP, indicating a link between stress hormones and hair loss.^[50,51] While a direct causal link with acne is lacking, stress exacerbates acne severity.^[19] According to a cross-sectional study, higher perceived stress scores strongly correlate with more severe acne.^[52] HPA-axis dysregulation is also implicated in chronic dermatoses: Psoriasis, SD, and rosacea (among others) are adversely affected by psychological stress.^[12] These results demonstrate that stress is not just a trigger but also a major disruptor of skin homeostasis.

In addition, macro-level stressors such as economic crises and financial insecurity can intensify these HPA-axis disruptions. For example, studies show that lower income levels and negative income changes are linked to chronically elevated cortisol accumulation.^[53] Occupational stress similarly modulates HPA outputs: Healthcare workers in high-risk roles (e.g., COVID-19 ICU nurses) have exhibited significantly higher hair cortisol than those in lower-stress positions.^[54] Moreover, an Italian study of security guards found higher salivary cortisol in night-shift workers than day workers. Night-shift guards had significantly elevated cortisol at the start (22:00) and end (06:30) of their shift compared to day-shift controls.^[55] Acute stress in some night roles can boost cortisol, and these findings indicate that socioeconomic and job-related stressors can further perturb HPA-axis balance and amplify hair and skin disorders.

Diagnostic and research advances

Interest in the HPA axis and its function in sebum and hair diseases has increased as novel diagnostic tools, including salivary cortisol and CRH, emerge as effective clinical biomarkers. Traditional cortisol assays using plasma and saliva are limited by their inability to reflect long-term levels and their susceptibility to confounding factors such as nicotine use, physical activity, and circadian rhythms. In contrast, hair cortisol concentration (HCC) acts as a more stable and non-invasive biomarker by gradually incorporating itself into growing hair. This provides an integrated measure of chronic stress. It is now increasingly used due to its painless and convenient collection. However, since hair cortisol levels depend on factors such as hair structure, growth rate, color, influence of cosmetic treatments, as well as external contamination, further research into these limitations is needed before HCC can be widely adopted as a diagnostic tool.^[56]

Diagnostic and laboratory evaluation criteria have also improved the early detection of hair and sebum changes. For example, combining the severity of alopecia tool (SALT) with quality-of-life measures or pairing SALT with scalp surface area has been validated as reliable in clinical trials for both adults and children. In addition, trichoscopy enables early scalp assessment, while biopsy is reserved for resistant or unexplained cases. However, data from Africa, South America, and Asia remain sparse, indicating a gap in global representation that limits generalizability.^[57]

Management and future therapies

Identification of stem cells such as Lgr6+ isthmus stem cells and Lgr5+ hair follicular stem cells has been instrumental in our understanding of the regeneration of hair follicles. The ability of these stem cells to adapt and regenerate hair after a wound can shape therapeutic approaches. However, wound-induced hair follicle neogenesis is a promising regenerative pathway requiring further study into age and wound-dependent outcomes.^[58]

Nanotechnology offers promising avenues for hair follicle regeneration through tools such as micro needles, nanoparticles (NPs), and exogenous stimulation. These technologies allow for regulated release, enhanced bioavailability, fewer adverse effects, and accurate medication administration. A number of nanosystems including polymeric, lipid, metallic NPs, quantum dots, and nanocrystals, are being tested for their ability to target hair follicles. All of them demonstrate successful follicular penetration. Due to their lipophilicity and structural similarities, lipid NPs seem to be the most promising.^[59] The lack of regulatory guidelines in the pharmacological and toxicological evaluation of NP-based medication delivery systems continues to prevent nanotechnology from being widely used, despite significant advancements and development.^[60] Establishing a regulatory framework is crucial for the clinical adoption of these therapies.

With associations being made between HCC and mental disorders such as post-traumatic stress disorder and depressive disorders, the need for interventions such as cognitive behavioral therapy (CBT), mental training, and relaxation techniques is growing.^[61] Studies regarding the use of CBT in dermatological disorders have shown considerable success, in acne and skin picking disorders, there was a notable reduction in skin picking as well as a 5.4-point greater reduction in depression scores defined by the beck depression inventory.^[62] CBT proved helpful in atopic dermatitis by reducing itch intensity and eczema severity, with even better outcomes when paired with topical therapy. In patients with psoriasis, there was noted improvement in quality of life, anxiety, and depression with better outcomes in combination with ultraviolet B phototherapy.^[63,64]

Occupational stress interventions: Individual-focused stress management programs (e.g., CBT and mindfulness) are being applied to high-risk professions. For instance, ICU staff who received a communication skills training grounded in CBT principles reported lower perceived stress.^[65] Systematic reviews also show that such workplace CBT-based programs can sustain reductions in stress symptoms for up to a year in healthcare workers.^[66] These findings underscore the value of offering stress-reduction interventions (like CBT) to clinicians and other high-stress occupations to potentially improve skin and hair health.

Due to the increased use of facial masks in light of the SARS-CoV-2 outbreak, there has been a significant rise clinical worsening of skin disorders such as chronic SD, rosacea, allergic contact dermatitis as well as irritant contact dermatitis, thus the need for preventive strategies such as using barrier creams, changing mask materials, and gentle skincare routines as well as routine changing of masks along with hand hygiene before wearing masks have been proposed to manage maskne and reduce skin flare-ups effectively.^[1,39]