Keywords
Skin-Whitening Products, Cortisol, Adrenal Suppression, BMI
This article is included in the Fallujah Multidisciplinary Science and Innovation gateway.
This cross-sectional study assessed the impact of long-term use of skin-whitening products containing corticosteroids on the function of the adrenal glands.
To assess the impact of extended use of corticosteroid-based whitening creams on serum cortisol levels and to examine the prevalence of adrenal suppression among habitual users.
This research, executed at the Hawija Technical Institute from January to April 2025, included 57 participants aged 20 to 40. Before enrolling, all participants gave their written consent. Individuals with chronic endocrine disorders or those receiving systemic corticosteroids were excluded. They were split into two groups: 38 regular (14 male and 24 female) users of skin-whitening creams (≥3 months) as the experimental group and 19 (7 male and 12 female) non-users as the control group. The Mindray CL-900i, a fully automated chemiluminescence immunoassay analyzer, was used to measure the levels of cortisol in the serum.
In comparison to controls (7.85 ± 3.54 μg/dL; p = 0.0004), users had a significantly lower mean cortisol level (4.25 ± 2.23 μg/dL), with 42% of users exhibiting cortisol <5 μg/dL, indicating adrenal suppression. There were no discernible variations in BMI between the groups or between male and female users. These results show that extended exposure to corticosteroids suppresses the hypothalamic-pituitary-adrenal axis.
Using skin-whitening creams that contain corticosteroids too often can make the adrenal glands work less well. It is suggested that public health measures be used to inform users about endocrine risks and to control these products.
Skin-Whitening Products, Cortisol, Adrenal Suppression, BMI
In many parts of the world, especially in Asia, Africa, and the Middle East, where lighter skin is frequently linked to social standing and beauty, skin-whitening creams have grown in popularity.1,2 Corticosteroids, hydroquinone, and mercury compounds are common active ingredients in these products. When used excessively or without medical supervision, these substances can cause serious systemic side effects.3,4
The effects of long-term use of corticosteroid-containing whitening creams on the endocrine system, especially the adrenal glands, are one of the main causes for concern.5,6 Local research has similarly observed endocrine dysregulation and HPA axis activation in patients with thyroid disorders in Kirkuk.7
The production of essential hormones like cortisol, aldosterone, and androgens is carried out by the adrenal cortex8–10. The hypothalamic-pituitary-adrenal (HPA) axis can be suppressed by exogenous corticosteroids that are absorbed through the skin, resulting in Cushing’s syndrome or adrenal insufficiency.11,12
Long-term topical steroid use has been linked to an increasing number of patients experiencing metabolic problems and adrenal suppression, according to recent clinical studies and case reports.13 Many over-the-counter whitening products are still unregulated, despite regulatory efforts, which puts the public’s health at serious risk.14
With an emphasis on the mechanisms of hormonal disruption and possible clinical outcomes, this study attempts to investigate the physiological effects of skin-whitening creams on adrenal gland function.15
The recovery of the hypothalamic–pituitary–adrenal (HPA) axis following corticosteroid administration is contingent upon the dosage, potency, and duration of use.16
• ACTH levels start to rise again in 1 to 4 weeks.
• Partial recovery can happen in 1 to 3 months.
• Full recovery can take 3 to 12 months, and in long-term high-potency use, suppression can last more than a year. To avoid an adrenal crisis, it is important to gradually taper off.17
Difficulties Associated with the Use of Corticosteroids or Skin-Whitening Creams. Using skin-whitening creams that contain corticosteroids can be very bad for your health. They might make your skin look lighter for a short time, but using them for a long time or without supervision can cause skin thinning, acne, striae, telangiectasia, and HPA axis suppression.18 A lot of people use these products without talking to a doctor first, usually because of cultural pressures or ads that aren’t true. Stopping them suddenly may cause rebound dermatitis or withdrawal symptoms. Overall, the misuse of these creams is a big medical and regulatory problem that needs more attention and control.19
The primary objectives of our study were to evaluate the impact of extended use of corticosteroid-containing skin-whitening creams on serum cortisol levels and adrenal gland function in habitual users.
Other research has shown that type 2 diabetic patients infected with intestinal parasites exhibit increased WBC and lymphocyte counts, which may reflect a cortisol-mediated stress response, suggesting that physiological stress from infection or chemical exposure such as skin-whitening creams can alter cortisol levels.20
This cross-sectional study was conducted from January to April of 2025. All the Fifty-seven participants both male and female, ages of 20 – 40 years. Everyone who took part gave their written consent before doing so. Individuals with chronic endocrine disorders or those undergoing systemic corticosteroid therapy were excluded. They were divided into two groups: an experimental group and a control group.
The sample size of 57 participants was established to represent the maximum number of eligible participants attainable during the study period, informed by prior analogous studies, thereby ensuring adequate statistical power (>80%) to identify variations in serum cortisol levels between users and controls.
Group 1 (Experimental group) included 38 participants who reported using skin-whitening creams regularly for at least three consecutive months. The products were taken from beauty salons as cosmetic mixture without any medical supervision. The experimental group was split up into 24 females and 14 males. Group 2 (Control group) consisted of 19 participants (7 male and 12 female) who reported never used any topical skin-whitening or corticosteroid-containing products. The unequal group ratio (1:2, 19 controls and 38 users) is based on the number of people who could participate and the fact that many people use skin-whitening cream regularly. It still gives us enough statistical power to make comparisons. Structured interviews were administered to each participant to gather data on cream usage and demographic attributes. The length of time people used the cream varied from 3 to 12 months. Prior to sample collection written informed consent was obtained from all participants involved in this study.
The sample size was established based on feasibility and prior analogous studies. Venipuncture was used to take blood samples (5 mL) from all participants between 8:00 and 10:00 in the morning. We let the samples clot at room temperature and then used a standard centrifuge to separate the serum.
This study concludes 57 participants (34 female and 23 male), that divided into experimental group 38 (24 female and 14 male) and control group 19 (12 female and 7 male), the two groups age were 22.92 ± 3.26 and 21.21 ± 2.30 years old respectively. Table 1 show these informations:
| Group | Age average ± SD | Male | Female | Total |
|---|---|---|---|---|
| Experimental group | 22.92 ± 3.26 | 14 | 24 | 38 |
| Control group | 21.21 ± 2.30 | 7 | 12 | 19 |
| Total | 21 | 36 | 57 |
The control group had a significantly higher mean cortisol level (7.85 ± 3.54 μg/dL) in comparison with the experimental group (4.25 ± 2.23 μg/dL) (normal range of morning cortisol 6-25 μg/dL). The experimental group’s hypothalamic-pituitary-adrenal axis was suppressed, as evidenced by the statistically significant difference (p = 0.0004), as shown in Table 2 and Figure 1.
| Group | Cortisol ± SD (μg/dL) | Min | Max | P-value |
|---|---|---|---|---|
| Experimental Group | 4.25 ± 2.23 | 0.4 | 9.05 | 0.0004 |
| Control Group | 7.85 ± 3.54 | 1.58 | 17.6 |
Adrenal suppression was indicated by cortisol levels below 5 μg/dL in about 42% of users and below 3 μg/dL in 18% as shown in Figure 2.
The mean cortisol level in the experimental group (users) was 4.06 μg/dL (SD ± 1.80) for females and 4.57 μg/dL (SD ± 2.88) for males. There are 24 women and 14 men among the participants. Cortisol levels ranged from a minimum of 1.68 μg/dL for females and 0.40 μg/dL for males to a maximum of 9.05 μg/dL and 9.04 μg/dL, respectively. There is no statistically significant difference in cortisol levels between male and female participants, according to Table 3 ’s p-value of 0.563 from an independent t-test that was used to compare the two groups.
| Gender | Mean ± SD | Min | Max | Count | p-value |
|---|---|---|---|---|---|
| Female | 4.0625 ± 1.803083 | 1.68 | 9.05 | 24 | 0.562951 |
| Male | 4.565 ± 2.881396 | 0.4 | 9.04 | 14 |
The mean BMI in the control group was 26.03 kg/m2 (SD ± 3.17), while in the experimental group it was 25.15 kg/m2 (SD ± 3.17) ( Table 4). Despite the control group’s marginally higher mean BMI, there was no statistically significant difference between the two groups (p = 0.330).
With mean values of 4.25 ± 2.23 μg/dL and 7.85 ± 3.54 μg/dL, respectively, the experimental group (users) had significantly lower serum cortisol levels than the control group (p = 0.0004). This significant difference implies that the experimental group’s hypothalamic-pituitary-adrenal (HPA) axis was suppressed. This finding is in line with earlier research that connected inappropriate or long-term topical corticosteroid use to adrenal suppression.21,22 According to dermatological and endocrinological literature, prolonged exposure to glucocorticoids, even through dermal absorption, can impair adrenal responsiveness.11,23 Which may lead to significant changes in systemic steroid levels, several factors, including skin integrity, steroid strength, and duration and frequency of use, all affect the absorption of corticosteroids by the skin, as recent pharmaceutical research has shown.24
Cortisol levels in 18% of users in our study were below 3 μg/dL, while 42% had cortisol levels below 5 μg/dL, which is consistent with rates of adrenal suppression.25,26
Below 3 μg/dL of cortisol levels in serum indicate inhibited adrenal function, while below 5 μg/dL concerned adrenal insufficiency typically.27
The analysis that gender-based exposed that the male participants of cortisol levels was (4.57 μg/dL) and that of female participants was (4.06 μg/dL) which did not mean statistically significantly (p = 0.563), demonstrating that the detected suppressive effect of the gland is not sex-related. This finding is in consistence with previous research finding that the biological sex of lower of an effect on the effects systemically of strong topical corticosteroids than the strength, surface area of application, and treatment length.28,29 The body mass index (BMI) of the control group average was higher rather at 26.03 kg/m2, while the average BMI of experimental group was 25.15 kg/m2. Though, the difference (p = 0.330) was not significant statistically. This suggests that BMI is improbable to have an effect on the detected cortisol variations. Epidemiological studies demonstrated similar results that have revealed that the inhibition of the HPA axis is not always associated with BMI in corticosteroid users.30
Following the use of topical corticosteroids for long period, the axis of HPA may need weeks to months for recovery, dependent on the potency, usage duration, and personal sensitivity. This reveals how essential it is to screen them and cease using gradually so that preventing adrenal crises.31
This study results highlight the evaluating adrenal function clinical importance in those that use skin-whitening products regularly which corticosteroids containing. Physicians should Pay attention that topical therapies excessive absorption can results in the malfunction of the adrenal glands. Cortisol testing regularly and patients teaching safe the usage of steroid are essential in adrenal crises preventing, especially in populations where supervision of the cosmetic steroid usage is prevalent. Also from the important responsibility of health authorities is the regulations tighten and labeling mandate unambiguous in order to overuse decrease.
To protect people and lower the risk of endocrine problems, the FDA, WHO, and other regulatory bodies have stressed the need for stricter oversight and public education about cosmetic products that contain corticosteroids.32
This study design does not allow for the examination of long-term corticosteroid effects or the recovery of the hypothalamic-pituitary-adrenal (HPA) axis following cessation. Second, the sample size is sufficient for detecting statistical differences, but it may limit the generalizability of the findings to broader populations. Third, self-reported data on the quantity and duration of cream usage may introduce memory bias. They also did not take into account other things that could affect cortisol levels on their own, like stress, medication use, and food.
Furthermore, the variations in the formulation and potency of unregulated whitening products were not analyzed, which could influence the extent of systemic absorption. While an independent t-test was utilized to compare groups, additional statistical methods, such as multiple regression, could enhance the management of potential confounders and facilitate a more thorough interpretation of the results. Considering the endocrine sensitivity exhibited by both genders, subsequent research should investigate whether sex-specific variations in skin permeability, corticosteroid metabolism, or hormonal fluctuations may influence systemic effects. To determine the causal relationships between topical corticosteroid application and adrenal suppression, subsequent research should emphasize longitudinal and interventional studies. To gain insights into the systemic effects and recovery duration of the HPA axis, biochemical analyses of the product’s composition and dose-response evaluations are advisable.
The study’s results indicate potential adrenal suppression, as they demonstrate a robust and consistent correlation between the habitual use of skin-whitening products and reduced cortisol levels. People who use these creams are more likely to get secondary adrenal insufficiency, which can be deadly if not treated. This study stresses how important it is to teach customers about the dangers that cosmetics can pose to the endocrine system.
Stricter laws governing the labeling and sale of skin-whitening products should be put into effect. Topical corticosteroids should only be used under a doctor’s care for diagnosed skin conditions, not for cosmetic whitening.
To more accurately describe the long-term effects of these practices on adrenal health, future research involving larger cohorts, hormonal panels (including ACTH), and longitudinal follow-up is advised.
The study protocol was approved by the Institutional Review Board of the Ethical Approval Committee, Center of Technical Research, Northern Technical University, Iraq (Approval No: 11, Date: 2 October 2024).
Figshare. The Effect of Whitening Creams Usage on the Adrenal Gland. https://doi.org/10.6084/m9.figshare.30840839.33
The project contains the following underlying data:
• BMI_Comparison_between_Control_and_Experimental_Groups Table 4.xlsx (this file contains calculated BMI values derived from the original height and weight data available in the same figshare repository which processed/summarized data rather than raw measurements.)
• Control group information (cortisol levels, age and gender).xlsx (raw cortisol levels, age, and gender data for the control group)
• Cortisol_Below5_and_Below3 in users Figure 2.xlsx (raw cortisol suppression data used to generate Figure 2)
• Cortisol_Comparison_by_Gender_in_Experimental_Group Table 3.xlsx (this file contains calculated cortisol comparison values derived from the original cortisol datasets available within the same figshare repository. It represents processed/summarized data rather than raw participant level measurements)
• Experimental group information (cortisol levels, age and gender).xlsx (raw cortisol levels, age, and gender data for the experimental group)
• Height_Weight_BMI_Table control group.xlsx (raw height, weight, and BMI data for the control group)
• Height_Weight_BMI_Table experimental group.xlsx (raw height, weight, and BMI data for the experimental group)
Figshare. The Effect of Whitening Creams Usage on the Adrenal Gland. https://doi.org/10.6084/m9.figshare.30840839.33
The project contains the following extended data:
• Participant_Form_Whitening_Cream_Study Questionnaire. docx (Questionnaire used to collect participant information)
• STROBE-checklist-v4-cross-sectional-whitening creams. doc (completed STROBE checklist for cross sectional study)
• Ethical Approval Whitening Creams. jpg (Ethical Approval document for the study)
The Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).
The authors would like to thank the staff who worked at the External Laboratory of Mr. Yasir Abd Dally for their help with gathering samples and doing lab tests.
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