title: Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?
abstract: OBJECTIVE
  To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE).
  
  
  METHODS
  Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed.
  
  
  RESULTS
  The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507).
  
  
  CONCLUSIONS
  The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.
authors.affiliation: Division of Rheumatology, Faculty of Medicine, University of São Paulo , Brazil.
authors.forename: D B
authors.initials: DB
authors.lastname: de Araujo
authors.forename: L Y S
authors.initials: LY
authors.lastname: Yamakami
authors.forename: N E
authors.initials: NE
authors.lastname: Aikawa
authors.forename: E
authors.initials: E
authors.lastname: Bonfá
authors.forename: V S T
authors.initials: VS
authors.lastname: Viana
authors.forename: S G
authors.initials: SG
authors.lastname: Pasoto
authors.forename: R M R
authors.initials: RM
authors.lastname: Pereira
authors.forename: P C
authors.initials: PC
authors.lastname: Serafin
authors.forename: E F
authors.initials: EF
authors.lastname: Borba
authors.forename: C A
authors.initials: CA
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D003338:Corpus Luteum / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008727:Methotrexate / Q000009:adverse effects*; D065851:Ovarian Reserve / Q000187:drug effects*
chemical_list: D054304:Anti-Mullerian Hormone; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone; D008727:Methotrexate