Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?

Author(s)

de Araujo, D. B. ^[1] ; Yamakami, L. Y. S. ^[2] ; Aikawa, N. E. ^[3] ; Bonfa, E. ^[4] ; Viana, V. S. T. ^[5] ; Pasoto, S. G. ^[6] ; Pereira, R. M. R. ^[7] ; Serafin, P. C. ^[8] ; Borba, E. F. ^[9] ; Silva, C. A. ^[10]

Affiliation

^[1] Univ Sao Paulo. Fac Med

^[2] Univ Sao Paulo. Fac Med

^[3] Univ Sao Paulo. Fac Med

^[4] Univ Sao Paulo. Fac Med

^[5] Univ Sao Paulo. Fac Med

^[6] Univ Sao Paulo. Fac Med

^[7] Univ Sao Paulo. Fac Med

^[8] Univ Sao Paulo. Fac Med

^[9] Univ Sao Paulo. Fac Med

^[10] Univ Sao Paulo. Fac Med

• Document type: Journal article
• Source: SCANDINAVIAN JOURNAL OF RHEUMATOLOGY; v. 43, n. 6, p. 503-511, 2014.
• Web of Science Citations: 11

Abstract

Objectives: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). Method: 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-Mullerian 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. (AU)

• FAPESP's process: 11/12471-2 - Ovarian reserve, antibody anti-corpus luteum and lower genital tract infection in adult women with systemic lupus erythematosus, Behçet's syndrome and Takayasu's arteritis
• Grantee: Clovis Artur Almeida da Silva
• Support Opportunities: Regular Research Grants