Clinical characteristics of rosacea in perimenopausal women

Rosacea is a chronic inflammatory skin disease and that can be classified into four broad subtypes: erythematotelangiectatic rosacea (ETR), papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea. Its pathogenesis may be related to genetic predisposition, immune system disorders, chronic inflammation, vascular, and nerve dysfunction. ¹ Perimenopause is a natural stage of the aging process, characterized by the gradual cessation of ovarian function and a substantial decline in estrogen levels. It typically occurs between the ages of 45 and 55, and lasts for 4 to 8 years. ² The incidence of rosacea rises in middle‐aged women, especially those aged 40 and 60. ³ And rosacea tends to be more severe in patients aged 45 and older, ⁴ many of whom are often in perimenopause. In addition, studies have found that hormonal imbalance is associated with the occurrence of rosacea. ⁵ Therefore, it seems reasonable to speculate that perimenopause and related hormonal changes may be one of the underlying mechanisms of rosacea in middle‐aged women.

In this observational study, patients were collected from the dermatology outpatient department of West China Hospital from January 2022 to January 2023. All enrolled patients signed an informed consent form. Inclusion criteria included: (a) meeting the diagnostic criteria of the 2019 National Rosacea Society Expert Committee, with each phenotype or subtype divided into three grades: mild, moderate, and severe; ¹ (b) being in the perimenopausal stage, including the menopause transition period and 1 year after menopause defined as “Reproductive Aging Workshop +10”. ² Exclusion criteria were: (a) use of oral or topical contraceptives or sex hormone preparations within the past 6 months; (b) presence of endocrine disorders affecting estrogen levels; (c) history of ovaries or uterus excision; (d) patients with thyroid diseases, liver and kidney diseases, cardiovascular and cerebrovascular diseases or malignant tumors. The Dermatology Quality of Life Index (DLQI) ⁶ and Rosacea‐specific Quality‐of‐Life instrument (RosQol) ⁷ were used to assess the quality of life(QOL) of the patients. The Hospital Anxiety and Depression Scale (HADS) was used to assess patients' anxiety and depressive states. ⁸ Blood samples were collected from all patients in the early morning after fasting. Estradiol (E2), follicle‐stimulating hormone (FSH), and testosterone (T) were measured using the electrochemiluminescence method on a ROCHE automatic electrochemiluminescence analyzer. Blood samples were collected during the follicular phase of menstruation, without any special requirement for menstruation cessation. T‐test and one‐way analysis of variance were used to compare the two groups and three groups of numerical data, respectively. The correlation of test variables is analyzed using step‐wise regression analysis. SPSS statistical software (Version 28, IBM) was used for data analysis.

Fifty‐nine patients with rosacea in the perimenopausal stage were enrolled in this study, with an average age of 48.42 ± 0.35 years (ranging from 45 to 55 years). Twenty‐five patients (42.4%) had menstrual cycle disturbance, and 34 patients (57.6%) had menstrual cessation. The QOL of perimenopausal women with rosacea was greatly affected. The total score of DLQI was 11.13 ± 1.17. The average total score of RosQol was 1.85 ± 0.72, with the score of emotion, symptom, and function being 1.81 ± 0.13, 1.80 ± 1.14 and 2.18 ± 1.15, respectively. Additionally, 45.8% of the patients had anxiety and 40.0% had depression.

All patients had persistent ETR. Among them, 42 individuals(71.2%) presented with moderate to severe ETR (Figure 1A). Thirty‐four patients (57.6%) developed PPR with eight of those patients having moderate to severe PPR (Figure 1B). The clinical features included are summarized in Figure 1C. The mean E2 level was 61.04 ± 7.27 pg/mL. Since the number of people with ETR was the largest in this study, we only analyzed differences in E2 levels between ETR severity. There were significant differences in E2 levels among different severity of ETR, with the E2 levels in moderate and severe groups being significantly lower than those in the mild group, which is shown in Table 1 and Figure 1D. There was no statistically significant difference between the FSH and T levels by severity, but it is worth noting that T levels were higher in moderate and severe rosacea patients (Figure 1F). According to step‐wise regression analysis, only E2 was correlated with the severity of ETR, and it was negatively correlated with a correlation coefficient of −0.021 (OR = 0.986;95%CI:0.976–0.996, p = 0.005). And the groups were divided into those with or without PPR. The results showed that the E2 level was statistically lower in the group with PPR as shown in Figure 1D.

FIGURE 1.

(A) ETR in perimenopausal women: Moderate to severe ETR in the midface(left); VISIA representation of the skin lesion within the white circle (top right); dermoscopic appearance of the skin lesion within the white circle (bottom right). (B) PPR in perimenopausal women: Moderate to severe PPR in the midface (left); VISIA (right). Figure 1 (C) Phenotypic distribution of rosacea in perimenopausal women: Persistent erythema, telangiectasia, burning, tingling, and dryness are the most common phenotypes. Figure 1 (D) Estradiol levels of rosacea in perimenopausal women: The more severe the ETR symptoms, the lower the E2 levels. There was a difference in E2 levels between those with and without PPR, and E2 levels were lower in those with PPR. (E) Testosterone levels of rosacea in perimenopausal women: Testosterone levels varied with the severity of ETR and the presence or absence of PPR. However, these variations were not statistically significant. Abbreviations: Estradiol (E2), follicle‐stimulating hormone (FSH), and testosterone (T). *:p＜0.05；**：p＜0.01.

TABLE 1.

The difference of sex hormone levels in different severity of ETR.

Variable	Total (n = 59)	Mild (n=17)	Moderate (n=30)	Severe (n=12)	p‐value
T (ng/mL)	0.13 ± 0.02	0.12 ± 0.02	0.12 ± 0.02	0.14 ± 0.03	0.77
E2 (pg/mL)	61.04 ± 7.27	95.82 ± 15.18	48.83 ± 8.57	42.28 ± 13.80	0.01
FSH (IU/L)	37.33 ± 5.43	35.45 ± 12.41	38.3 ± 7.42	37.56 ± 9.22	0.98

Note: Data are mean  ±  standard error(SE).

cE2, Estradiol, FSH, follicle‐stimulating hormone, and T, testosterone; ETR, erythematotelangiectatic rosacea. Description: Among T, E2, and FSH in ETRs of varying severity, only the difference in E2 was statistically significant.

The “Estradiol Protective Hypothesis” is gaining momentum, suggesting that estrogen plays an important protective role in maintaining optimal skin physiology by regulating antioxidant activity, hindering telomere shortening, inhibiting NF‐κB, and directly curbing oxidative stress. And after women enter perimenopause, the scarcity of estrogen may lead to age‐related skin alterations, such as compromised skin barrier function, decreased antioxidant function, heightened vulnerability to bruising, and reduced collagen synthesis. ⁹ These changes are likely to exacerbate the risk and severity of dermatosis. Moreover, estrogen also affects immune function, ¹⁰ and immune dysfunction is a significant causative factor of rosacea. Taken together, the decrease in estrogen levels during menopause may contribute to the higher incidence of the ETR subtype in perimenopausal women. However, this study is not without its limitations. Firstly, the sample size was somewhat limited, which may have engendered bias and errors in the findings. Additionally, the study was confined solely to perimenopausal female patients, and further research is needed to ascertain the applicability of these findings to other demographics. Moreover, since only estradiol was considered in the study, other potential factors may have skewed the results. Estrogen potentially acts as a safeguard for perimenopausal women. This study provides a novel idea and direction for the mechanism of estrogen in the pathogenesis of rosacea and the potential of estrogen regulation in the treatment of rosacea.

CONFLICT OF INTEREST STATEMENT

The authors have no conflict of interest to declare.

ETHICS STATEMENT

The study was approved by the Medical Ethics Committee of the West China Hospital of Sichuan University (approval number: 2022 (190)). All enrolled patients signed the informed consent form.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.