Ovarian dysfunction in adolescent girls with autoimmune rheumatic diseases

The demographic features and BMI of participants

Twenty-one adolescent girls with JSLE were included, the median of their current age, the age of disease onset, and the duration of disease were 16, 13, and 2 years, respectively. Their body mass index (BMI) ranged between 18 and 30 kg/m2. Meanwhile, twenty-three girls were enrolled with JIA (8 cases with oligo-articular subtype, 10 patients with poly-articular JIA, 3, and 2 children had enthesitis-related arthritis, and systemic JIA, respectively). The median of their current age was 14 years. The median of their age at the disease onset and disease duration were 11 and 4 years, respectively. Their BMI was between 17 and 32 kg/m2. The demographic features of JDM cases are shown on Table 1. The disease onset, diagnosis, and the disease duration were significantly different between JSLE and the other groups.

Table 1 Demographic features, disease onset, diagnosis, duration, and clinical features among adolescent girls with autoimmune rheumatic diseasesThe clinical features, disease activity, damage indices, and the treatment of ARD

The frequencies of clinical presentations of these adolescent girls were summarized on Table 1 and the most common reported manifestation among all diseases was arthralgia/arthritis. The disease activity, damage parameters, and physician assessment of disease activity states for JSLE, JIA, and JDM were displayed on Table 2. Concerning the lines of management, they varied according to the disease and its severity ranging between steroid (oral or pulses), methotrexate, hydroxycholoroquine, azathioprine, mycophenolate mofetil, or intravenous cyclophosphamide (CYC).

Table 2 Disease activity, damage indices, and physician assessment of disease states among adolescent girls with autoimmune rheumatic diseasesThe pattern of menstrual and pubertal changes of ARD

The median age of menarche for patients with JSLE was similar to JIA and JDM groups and it occurred around the age of 12 years. The median of the menstrual blood flow was the same in 3 groups (5 days). The frequency of dysmenorrhoea was 33.3% and 34.8% in JSLE and JIA, respectively. Ten patients with JSLE (47.6%) had menstrual abnormalities (primary amenorrhea (3 cases), polymenorrhea (2), and oligomenorrhea (5)), whereas only four JIA (17.4%) and 1 JDM girls had these alterations without significant difference between the three groups regarding the pattern of menstrual changes (Table 3). Delayed menarche was found in 4 patients (8.5%); 3 of them with JSLE.

Table 3 Pattern of puberty and menstrual changes among adolescent girls with autoimmune rheumatic diseases

According to the Marshall and Tanner’s staging of puberty [17], the median of breast, pubic, and axillary hair stages were 4, 3, and 3, respectively in JSLE that was comparable with JIA and JDM cases. The median of the age at the puberty onset was 12 in JSLE; similarly, it was 12 in JIA and JDM girls. There were 3 JSLE, 2 JIA, and 1 JDM patients with delayed puberty. No difference was observed between the studied groups in the puberty features (Table 3).

Hormonal profile and ultrasound features of ARD

Low levels of FSH, LH, and E2 were detected in 7, 6, and 2 cases, respectively, but serum prolactin was elevated in 2 cases of all ARDs. However, the median of FSH, LH, E2, and prolactin were comparable in all studied groups. The median of the US diameters of the endometrium, right, and left ovarian volumes was similar in the three diseases (Table 4), but US depicted infantile uterus and ovaries in 4 cases, 3 of them were JSLE and 1 had chronic JDM course.

Table 4 Disease activity, damage indices, hormonal assessment, ultrasound evaluation, and treatment lines in relation to menstrual cycle among casesJSLE girls with menstrual abnormalities versus normal cycles

The median of the disease duration of JSLE with menstrual abnormalities versus normal cycles was similar. The median of the age at menarche was also alike. Regarding the age of puberty onset, it was significantly delayed in those with irregular cycles. The median of SLICC/ACR damage index was statistically higher in JSLE with abnormal menstrual cycles, but the SLEDAI-2 K did not reach statistically significant difference. The cumulative steroid dose was much higher in those with menstrual abnormalities versus regular cycles (p < 0.05) that was statistically differ than JIA or JDM cases. No significant differences were found in the other lines, CYC use, or its cumulative dose in JSLE patients with menstrual abnormalities versus regular cycles (Table 4).

The median of FSH, LH, E2, and prolactin were alike in all groups without a statistical significant difference. Similarly, the US diameters of the endometrium and ovarian volumes were comparable in the two groups (Table 4).

Apart from the onset of puberty, no statistical correlation was observed between the age of the menarche of JSLE cases and the disease duration, SLEDAI-2 K, and the cumulative dose of steroid (Table 5).

Table 5 Correlation between the age of menarche, disease parameters, and the cumulative doses of steroidJIA with menstrual abnormalities versus normal cycles

The median of the disease duration, age at menarche, and age of puberty onset were similar in both subgroups. Also, the median of disease activity and damage indices were not statistically significant between those with abnormal menstrual cycles and regular ones. No significant differences were observed in the cumulative steroid dose or methotrexate use in JIA cases. The median of FSH, LH, E2, and prolactin were similar in both JIA subgroups. Likewise, the US features did not differ between the two groups (Table 4). No statistical correlation was detected between the age of menarche of JIA cases and the disease duration, JADAS-10, and steroid use except for the puberty onset (Table 5).

JDM with menstrual abnormalities versus normal cycles

No significant differences were found between JDM cases with menstrual abnormalities and those with regular cycles regarding the demographic features, age of menarche, onset of puberty, disease assessment indices, management lines, hormonal profile, or the US findings. However, the cumulative steroid dose was statistically higher in JDM compared to JIA patients (Table 4). A statistical correlation was observed between the age of menarche of JDM cases and the studied parameters, but it was not correlated to the cumulative dose of steroid (Table 5).

Regression analysis for menstrual abnormalities prediction in JSLE patients

In the logistic regression model, the significant predictor for menstrual abnormalities in JSLE was SLICC/ACR damage index (≥ 1; p = 0.021). However, the disease duration and cumulative dose of steroid were not detected as independent risk factors for menstrual irregularities on regression analysis (Table 6).

Table 6 Predictors of menstrual abnormalities among JSLE adolescent girls

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