Assessment of plasma testosterone, estradiol, and progesterone levels in Vietnam female patients with moderate to severe acne vulgaris

Introduction

Acne is a chronic inflammatory disorder of the pilosebaceous unit with various manifestations, including non-inflammation and inflammation lesions. Collier et al. (2008) investigated 1013 Americans aged 20 years and older; 73.3% (744) reported ever having acne, and more women suffer from acne than men.¹ Four major factors involved in acne pathogenesis are excessive sebum production, follicular hyperkeratinization, hyper-colonization of the duct by Cutibacterium acnes (formerly Propionibacterium acnes), and the production of inflammation.² Moreover, the hormone plays a part role in the pathogenesis of acne. Some studies found that acne had a relationship with hyperandrogenemia in female patients.³ Estradiol, the primary female sex hormone known as the major active estrogen, forms in absolute plasma levels and estrogenic activity during human female reproductive years. Supplying sufficient amounts of estrogens will decrease sebum production and may act by suppressing androgen production by inhibiting the pituitary from secreting gonadotropin.⁴ The effect of progesterone on sebaceous glands was still disputed. Some authors have blamed progesterone for the change in sebum production in females during the menstrual cycle. However, this theory has not been proved experimentally.⁵ Therefore, we conducted this study to evaluate the plasma testosterone, estradiol, and progesterone levels and the correlation of hormonal alterations with the severity of acne in women with acne vulgaris.

Materials and methods

The cross-sectional study was conducted on 140 female patients diagnosed with acne vulgaris and 70 healthy females. Patients were recruited from the clinic of the Dermatology and Venereology department, Military hospital 103, VMMU, from January to October 2019. Approval was obtained from the ethics committee of the Hanoi Department of Science and Technology. Written informed consent for publication of the patients’ details was obtained from the patients.

We selected female acne patients aged between 16 and 25 who had not received drugs causing acne (glucocorticoids, lithium, isoniazid, phenytoin, selective reuptake serotonin inhibitors) or hormonal therapy (hormonal contraceptive and anti-androgen therapy) for at least three months before joining the study. Healthy volunteers without acne, pregnancy, or lactation served as the control group. None of the participants had been treated with hormonal treatment at this time of the study. All patients of each group were asked about history taken, throughout local and general clinical examinations, to rule out any suspected similar diagnosis or other local and systemic disorders which contraindicate the patients from participating in this study. PCOS was also excluded by the manifestation of hyperandrogenism (hirsutism, oligomenorrhea) and confirmed with transvaginal and pelvic ultrasound.

Data analysis

Statistical analyses were done by using SPSS software version 22.0. Data were presented as percentages for qualitative variables and mean and standard deviation for quantitative variables. Comparing two means using the student t-test. The relationship between categorical variables was analyzed by using the Chi-square test. P values of less than 0.05 were considered to be significant.

Results

The study was conducted at OPD of the Dermatology and Venereology department, Military hospital 103, VMMU, Vietnam. The healthy volunteers were recruited from the community, and female patients with acne vulgaris were selected randomly as the study group. Two hundred and ten female participants were enrolled and divided into three groups, including moderate acne, severe acne groups, and healthy control. The mean age of patients for the acne group was 21.03±2.47 years; for the controls, it was 20.68±2.57 years ranging from 18 to 25 years (Table 1).

Data showed that sixty-five percent had a duration from one to two years. Meanwhile, patients suffering from acne for more than two years accounted for 2.86 percent. Most patients (50.71%) occurred acne from 20-24 years old. All cases presented comedones, followed by 80.71% of cases that had papules, and 61.43% had pustules. The highest percentage of acne lesion locations were on the cheek and forehead, with 67.86% and 53.57%, respectively. It was found that moderate and severe acne groups accounted for an equal percentage of 50% (Table 2).

Plasma testosterone concentrations in moderate and severe groups were 56.92±27.64 ng/dL and 60.71±25.85 ng/dL, respectively. Although the mean concentrations were all in the normal range, they were statistically significantly higher than the controls at 38.35±10.09 ng/dL. Plasma estradiol levels in moderate and severe groups were 325.12±91.79 pmol/l and 305.26±83.01 pmol/l subsequently, and in the healthy group, were 368.6±58.34 pmol/l. This reduction of estradiol level in female acne patients was statistically significant. Plasma progesterone concentrations in moderate, severe acne and control groups were 0.59±0.39 ng/mL, 0.65±0.40 ng/mL, and 0.58±0.11 ng/mL, respectively. The mean levels in female acne patients were higher than in controls; however, the difference was not significant. It was not found the different in mean plasma hormonal levels between moderate and severe acne groups (Table 3).

Regarding hormonal alterations, 33.57 percent of female acne patients had abnormal plasma hormonal levels of more than one biochemical parameter. 20.71% had plasma testosterone levels increase, 2.14% were a rise in estradiol levels, and 11.43% for progesterone elevation (Table 4).

Discussion

In this study, the mean age in the acne groups was 21.03±2.47 years, younger than the previous study, with a mean of 26.64 years.⁵ Most patients (50.71%) occurred acne from 20-24 years old with a duration between 1-2 years, accounting for the highest percentage with 65%. It was found that 32.4% had a duration of less than one year, and 2.86 percent suffered from acne for more than two years.

In literature, acne lesions often occur at sites with a risk of the pilosebaceous unit. In our study, the cheek and forehead were involved with the highest percentage (67.86% and 53.57%, respectively). Lesions on the chest and back accounted for 32.14% and 37.14%. Regarding fundamental lesions, both inflammatory and non-inflammatory lesions were all seen. Comedones were found in all patients, followed by 80.71% suffering from papules and 61.43% having pustules.

Plasma testosterone levels were significantly increased in female patients with moderate to severe acne vulgaris compared to the controls. Although the mean testosterone level was in the normal range, this elevation was statistically significant. It can be explained that androgen bioactivity depends on the amount of plasma hormonal levels and the affinity to specific receptors, the number of receptors, or metabolism in binding sites. Our result was corroboration by the study done by Wei et al.⁷ However, in the study by Cetinozman⁸ and Akdogan,⁹ no significant change in testosterone levels was found between the acne and control groups. The discrepancy among the research results can be explained that the numbers of samples of the previous authors were not large enough, and the method of grading the severity of acne disease between the studies was based on different scales. Furthermore, anti-androgen therapy improved acne lesions in patients with polycystic ovary syndrome,¹⁰ which shows the critical role of androgen in the pathogenesis of acne.

In our study, the percentage of hormonal alteration in at least one parameter in female patients with acne vulgaris was 33.57%. 20.71% had plasma testosterone levels increase, 2.14% were a rise in estradiol concentrations and 11.43% for progesterone elevation (Table 4). In 2013, da Cunha et al. found that 56.52% of cases changed at least one androgen hormone, and the rate of androgenism was 10.77%.⁵ The literature reveals that hormonal disorders such as PCOS have a relationship with acne as the clinical manifestation of this disease. In our study, all patients were examined to rule out hirsutism and took transvaginal and pelvic ultrasounds to find any changes in ovaries. However, the limitation of our study was that patients were screened at one point without follow-up hormonal disorders. Therefore, we theorized that hyperandrogenism without hirsutism might be a subclinical sign for early diagnosis of hormonal disorders.

The role of estradiol in the pathogenesis of acne vulgaris is not elucidated. We hypothesize that estrogens might impact sebum secretion by three mechanisms: the opposition of androgens within the sebaceous glands, inhibition of gonadal androgen production via a negative feedback mechanism on gonadotropin release, and affects genes that play a role in sebaceous gland growth and lipid production.¹¹ In our study, plasma estradiol levels in moderate and severe groups were significantly decreased compared to the healthy group. This result was in accordance with the observation of the study done by Wei et al.⁷

The progesterone effect on acne remains unclear. However, some studies show that progesterone can reduce androgen effects by inhibiting the 5-ARD enzyme or androgen receptors.¹² The fluctuation of sebum production in women during the menstrual cycle and premenstrual cyclic flare has partly been associated with progesterone. Some progestins lead to an exacerbation of acne by interacting with androgen receptors.^12,13 In our study, there was no statically significant difference between moderate to severe acne groups and controls in terms of plasma progesterone levels. In contrast to our study, Bakry et al. claimed that the progesterone levels in female acne patients were higher than in the control group.² It was similar to the study by Arora et al.¹⁴ The difference in results between our study and other studies can be explained by the different days of hormone tests in the menstrual cycle and different inclusion criteria. Arora¹⁴ and Bakry² investigated plasma hormones during the luteal phase of menses. Meanwhile, we performed in the follicular phase of menses.

Our study had some limitations. As literature reviews, plasma salivary hormone levels such as progesterone and estradiol fluctuate during menstrual cycles. To minimize these effects, we took samples at 8 a.m. on the 2-4^th day of menses, the early follicular phase of the menstrual cycle, during which plasma hormonal levels remain relatively stable. In our study, hormonal alterations showed a relationship with acne vulgaris. Therefore, large-scale cross-sectional studies are needed to confirm the correlation between acne and hormonal abnormalities. Further prospective studies are to follow up on acne cases having plasma hormonal alterations without clinical presentation, as well as evaluate the clinical outcomes of targeted therapies.

Conclusion

Our study showed that female patients with moderate to severe acne vulgaris had abnormalities in plasma testosterone and estradiol levels. These abnormalities might be part of the pathogenesis of acne vulgaris, even when the mean levels were in the normal range.

Data availability