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 cortex ^{8– 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.

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 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:

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.

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.

The mean BMI in the control group was 26.03 kg/m ² (SD ± 3.17), while in the experimental group it was 25.15 kg/m ² (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/m ², while the average BMI of experimental group was 25.15 kg/m ². 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

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).