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Table 1 Impact of autoimmune rheumatic diseases on puberty-related outcomes (listed as per year of publication)

From: A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases

First author, year of publication Type of study Country of origin Participants, disease
N (F:M)
N (F:M)
Ethnic group Puberty-related outcomes measured Results Quality of the study using the Newcastle-Ottawa scale /9
El Badri et al., 2014 [26] Cross-sectional Morocco
Single centre
40 (18:22) JIA patients
11 – systemic
9 – oligoarthritis
17 – RF positive polyarthritis
1 – RF negative polyarthritis
1 – enthesitis-related arthritis
1 – psoriatric arthritis
Age 11 ± 4.23 years
74 children Moroccan Age at puberty onset and menarche Delayed puberty was observed in JIA patients (15%) vs. controls (1%) (P = 0.005).
Mean age at menarche was 0.7 years later in patients (12.33) compared to healthy controls (11.62).
There was an association between the dose of corticosteroids (P < 0.05) and earlier age at the administration of corticosteroids (P < 0.05) with delayed puberty in boys.
Maher et al., 2013 [27] Cross-sectional Egypt
Single centre
80 (45:35) JRA patients
30 – pauci-articular
33 – polyarticular
17 – systemic
Age 13.29 ± 2.42 (range 8–16) years
80 age- and sex-matched healthy controls Not stated Age at onset and completion of puberty as measured by Tanner staging G2–5 of genital development, presence/absence of pubic hair, and age of menarche.
BMI and weight
Onset of puberty (attainment of stage G2 of genital development) delayed in all JRA groups compared to HC.
Age of menarche delayed in all JRA groups compared to HC.
Stage G4 not obtained by 16 years in poly-JRA male or female.
No JRA groups reached stage G5 by age 16 years.
Weight and BMI significantly lower in JRA patients compared to HCs.
Rygg et al., 2012 [13] Prospective cohort Europe
Multi centre: PRINTO study (Paediatric rheumatology international trials)
331 (276:55) JSLE patients
Median age 13.9 (1st quantile 11.9, 3rd 15.8) years
No; compared to literature or target based on parents Not stated Age at puberty onset, menarche and Tanner staging (n = 147, only females)
Height (n = 331)
Measurements at baseline, 6, 14 and 26 months
Delayed pubertal onset was found in 15.3% of females and 24% of males.
Delayed/absent menarche was found in 21.9% of females.
Some degree of delayed pubertal development was found in 36.1% of the females and 44% of the males.
Growth failure (defined as parent-adjusted height z-score < − 1.5) was seen in 16.9% of females and 22.4% of males.
Females with prepubertal onset (age < 8 years) had significantly lower parent-adjusted height scores (median baseline z = − 1.99) throughout follow-up.
Females with post-pubertal onset (age  ≥ 13 years) had parent-adjusted height scores near the age-matched reference with no further decrease throughout follow-up.
Females with peri-pubertal onset showed a decrease in parent-adjusted height scores over time.
Aggarwal et al., 2011 [28] Prospective cohort North-West India
Single centre
70 (0:70) JRA patients
24 – pauci-articular
32 – polyarticular
24 – systemic
Age range 9–17 years
134 ‘normal’ boys from a previous study in the same area Not stated Age at completion of puberty as measured by Tanner staging G2–5 of genital development, and presence or absence of facial, pubic and axillary hair at 6-month intervals None of the JRA patients obtained stage G5 of genital development by age 17, compared to the average age of HCs of 15.2 years. Those with systemic JRA didn’t reach stage G4 of genital development by age 17.
Puberty initiation (stage G2) was earliest among patients with systemic JRA (10.8 ± 1.3 years), and first appearance of pubic/facial/axillary hair was also earlier among these patients compared to pauci- and poly-JRA.
Aggarwal et al., 2011 [29] Prospective cohort North-West India
Single centre
70 (0:70) JRA patients
24 – pauci-articular
32 – polyarticular
24 – systemic
Mixed socio-economic background
Age range 9–17 years
No; compared to literature data from well-off Indian boys and American boys Not stated Growth velocity, measured by body weight and height at 6-month intervals Patients from all subtypes of JRA measured lighter and shorter than in literature reported well-off Chandigarh, affluent Indian and American boys.
Boys with polyarticular and systemic onset JRA were shorter than those with pauci-articular JRA, until 15 years and 12 years, respectively.
Onset of peak height velocity in boys with polyarticular JRA was delayed (i.e. 12.5 years) compared to boys with pauci-articular JRA (i.e. 11.5 years). Attainment of Peak Weight Velocity in boys with polyarticular JRA (i.e. 13.5 years) was also delayed by 1 year when compared to those with pauci-articular type (i.e. 12.5 years).
Medeiros et al., 2009 [30] Cross-sectional Brazil
Single centre
30 (30:0) JSLE patients
Mean age 17.4 ± 3.2 years
30 age- and sex-matched healthy controls Not stated Age at menarche, menstrual and hormonal alterations Age at menarche was higher in JSLE than controls (13. ± 1.4 vs. 11.56 ± 1.5 years, P = 0.0008).
Menstrual abnormalities and longer length cycles were more frequent in JSLE than controls (63% vs. 10%, P = 0.0001; 23% vs. 0%, P = 0.0105, respectively).
The median of FSH was significantly higher in patients with JSLE compared with controls (4.6 vs. 3.4 IU/L, P = 0.0207), and the median of progesterone was lower (32.5 vs. 70 ng/mL, P = 0.0033).
The median of LH was lower in patients with JSLE with menstrual abnormalities versus normal cycles (2.9 vs. 5.5 IU/L, P = 0.019).
Silva et al., 2002 [31] Retrospective cohort Brazil
Single centre
23 (23:0) SLE patients
Age range 16.75–22.83 years
No; compared to historical healthy control data on 2578 Brazilian adolescents Not stated Gonadal function and age of menarche Mean age of menarche (13.5 ± 1.4 years) in SLE patients was greater than that of healthy Brazilian adolescents (12.5 ± 1.3 years; P = 0.0002).
70% of SLE patients showed normal gonadal function.
Gutiérrez-Suárez et al., 2006 [32] Cross-sectional 39 Countries across Europe, North & South America, Asia and Oceania
1015 (846:169) JSLE patients
Mean age 15.9 ± 4.1 (range 2.4–34.8) years
No; compared to mean for age according to literature Not stated Growth (n = 943) defined by height
Puberty stage (n = 556) defined by development of secondary sexual characteristics
15.3% had growth failure (height > 2 SD below mean for age)
11.3% had delayed puberty (secondary sexual characteristics > 2 SD below the
mean for age by Tanner staging).
The frequency of both growth failure (P < 0.001) and delayed puberty (P = 0.02) increased significantly with the increase in disease duration.
Fraser et al., 1988 [33] Retrospective cross-sectional Massachusetts USA
Two centres
68 (68:0) JRA patients
35 – pauci-articular
18 – polyarticular
15 – systemic
Age not reported
46 patient sisters (all without JRA)
(one a mono-zygotic twin)
Caucasian Association between age at disease onset, JRA diagnosis on age of menarche Girls with JRA have later mean age of menarche 13.2 years vs. 12.5 years for siblings (p = 0.015) irrespective of recorded steroid use (in 29.4% JRA patients)
Age of disease onset was not an important predictor of age of menarche.