Rheumatology International

, Volume 28, Issue 6, pp 567–571 | Cite as

Ovarian failure in SLE patients using pulse cyclophosphamide: comparison of different regimes

  • Simone Appenzeller
  • Paula F. Blatyta
  • Lilian T. L. Costallat
Original Article

Abstract

The objective of this study was to determine the frequency and risk factors of early ovarian failure in systemic lupus erythematosus (SLE) women treated with cyclophosphamide (CY). We further tried to determine if there was a reduction of ovarian failure in recent years, due to reduction in the CY dose. We reviewed the charts of all women below 40 years of age who received intravenous CY pulse therapy. In order to be included, the patients must have finished CY treatment before completing 40 years. Patients were divided into two groups: Group A (57 patients), patients who were treated with 0.75 mg/body surface; Group B (50 patients), patients treated with 0.5 mg/body surface. Fifty patients with similar age distribution who never received CY were selected from the database as a control group (Group C). The Chi-square test was applied to compare the categorical variables of the groups and whenever needed, the Fisher’s Exact test was used. We observed similar age distribution and disease duration at disease onset between groups. Also, no differences regarding the age at menarche, total prednisone dose, and SLICC-ACR/DI scores were observed at disease onset between the three groups. In group A, ten (17.5%) patients refereed sustained amenorrhea, independently associated with treatment duration (P = 0.001), total intravenous cyclophosphamide (IV-CF) dose (P = 0.02), older age at disease onset (P = 0.04). Seven (12.3%) patients referred transient amenorrhea. Transient amenorrhea was related to CY treatment duration (P = 0.017). In group B, no patient reported sustained amenorrhea and 10 of 50 (20%) patients referred transient amenorrhea, related to CY treatment duration (P = 0.017). The most important risk factors for menstrual abnormalities were duration of treatment and cumulative dose of CY. Lower CY dose reduced the number of premature ovarian failures significantly in this cohort.

Keywords

SLE Amenorrhea Cyclophosphamide 

References

  1. 1.
    Cervera R, Khamashtra MA, Font J et al (1993) Systemic lupus erythematosus: clinical and immunological patterns of disease expression in a cohort of 1,000 patients. Medicine 72:113–124PubMedCrossRefGoogle Scholar
  2. 2.
    Balow JE, Austin HA, Tsokos GC, Antonovych TT, Steinberg AD, Klippel JH (1987) NIH conference: lupus nephritis. Ann Intern Med 106:79–94PubMedGoogle Scholar
  3. 3.
    Neuwelt CM, Lacks S, Kaye BR, Ellman JB, Borenstein DG (1995) Role of intravenous cyclophosphamide in the treatment of severe neuropsychiatric systemic lupus erythematosus. Am J Med 98:32–41PubMedCrossRefGoogle Scholar
  4. 4.
    Boumpas DT, Austin III HA, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, Balow JE (1992) Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 340:741–745PubMedCrossRefGoogle Scholar
  5. 5.
    Boumpas DT, Barez S, Klippel JH, Balow JE (1990) Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus. Ann Intern Med 112:674–677PubMedGoogle Scholar
  6. 6.
    Fukuda M, Kamiyama Y, Kawahara K, Kawamura K, Mori T, Honda M (1994) The favorable effect of cyclophosphamide pulse therapy in the treatment of massive pulmonary hemorrhage in systemic lupus erythematosus. J Pediatr 153:167–170CrossRefGoogle Scholar
  7. 7.
    Schroeder JO, Euler HH, Loffler H (1987) Synchronization of plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus. Ann Intern Med 107:344–346PubMedGoogle Scholar
  8. 8.
    Valeri A, Radhakrishnan J, Estes D, D’Agati V, Kopelman R, Pernis A, Flis R, Pirani C, Appel GB (1994) Intravenous pulse cyclophosphamide treatment of severe lupus nephritis: a prospective five-year study. Clin Nephrol 42:71–78PubMedGoogle Scholar
  9. 9.
    Austin III HÁ, Klippel JH, Balow JE, Le Riche NGH, Steinberg AD, Plotz PH, Decker JL (1986) Therapy of lupus nephritis––controlled trial of prednisone and cytotoxic drugs. N Engl J Med 314:614–619PubMedCrossRefGoogle Scholar
  10. 10.
    Houssiau FA, D’Cruz DP, Haga HJ, Hughes GRV (1991) Short course of weekly low-dose intravenous pulse cyclophosphamide in the treatment of lupus nephritis: a preliminary study. Lupus 1:31–35PubMedCrossRefGoogle Scholar
  11. 11.
    Kumar R, Biggart JD, McEvoy J, McGeown MC (1972) Cyclophosphamide and reproductive function. Lancet 1:1212–1214PubMedCrossRefGoogle Scholar
  12. 12.
    Martin F, Lauwerys B, Lefebvre C, Devogelaer JP, Houssiau FA (1997) Side-effects of intravenous cyclophosphamide pulse therapy. Lupus 6:254–257PubMedCrossRefGoogle Scholar
  13. 13.
    Mok CC, Lau CS, Wong RWS (1998) Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum 41:831–837PubMedCrossRefGoogle Scholar
  14. 14.
    McDermott EM, Powell RJ (1996) Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide. Ann Rheum Dis 55:224–229PubMedCrossRefGoogle Scholar
  15. 15.
    Langevitz P, Klein L, Pras M, Many A (1992) The effect of cyclophosphamide pulses on fertility in patients with lupus nephritis. Am J Reprod Immunol 28:157–158PubMedGoogle Scholar
  16. 16.
    Huong DL, Amoura Z, Duhaut P, Sbai A, Costedoat N, Wechsler B, Piette JC (2002) Risk of ovarian failure and fertility after intravenous cyclophosphamide. A study in 84 patients. J Rheumatol 29:2571–2576PubMedGoogle Scholar
  17. 17.
    Warne GL, Fairley KF, Hobbs JB, Martin FIR (1973) Cyclophosphamide induced ovarian failure. N Engl J Med 289:1159–1162PubMedCrossRefGoogle Scholar
  18. 18.
    Uldall PR, Kerr DNS, Tacchi D (1972) Sterility in cyclophosphamide. Lancet 1:693–694PubMedCrossRefGoogle Scholar
  19. 19.
    Wang CL, Wang F, Bosco JJ (1995) Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus. Lupus 4:11–14PubMedCrossRefGoogle Scholar
  20. 20.
    Boumpas DT, Austin HÁ, Vaughn EM, Yarboro CH, Klippel JH, Balow JE (1993) Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 119:366–369PubMedGoogle Scholar
  21. 21.
    Fogelman I (1996) The effects of oestrogen deficiency on the skeleton and its prevention. Br J Obstet Gynaecol 103(14):5–9PubMedGoogle Scholar
  22. 22.
    Van Der Schoun YT, Van der Graaf Y, Steyeberg EW, Eijkemans JC, Banga JD (1996) Age at menopause as a risk factor for cardiovascular mortality. Lancet 347:714–718CrossRefGoogle Scholar
  23. 23.
    Tan EM, Cohen AJ, Fries JF (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRefGoogle Scholar
  24. 24.
    The Committee on Prognosis Studies in SLE, Bombardier C, Gladman DD, Urowitz M, Caron D, Chang C (1992) Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 35:630–640PubMedCrossRefGoogle Scholar
  25. 25.
    Gladman D, Glinzler E, Goldsmith C et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–378PubMedCrossRefGoogle Scholar
  26. 26.
    Brandt JT, Triplett DA, Scharer I (1995) Criteria for the diagnosis of lupus anticoagulant: an update. Thromb Haemost 74:1185–1190PubMedGoogle Scholar
  27. 27.
    Tincani A (2001) Cyclophosphamide therapy induces ovarian failure in premenopausal women affected by systemic lupus erythematosus. Clin Exp Rheumatol 19:490–491PubMedGoogle Scholar
  28. 28.
    Blumenfeld Z, Shapiro D, Shteinberg M, Avivi I, Nahir M (2000) Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy. Lupus 9:401–405PubMedCrossRefGoogle Scholar
  29. 29.
    Pasoto SG, Mendonca BB, Bonfa E (2002) Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: clinical, hormonal and therapeutic associations. Lupus 11:175–180PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Simone Appenzeller
    • 1
    • 2
    • 3
  • Paula F. Blatyta
    • 2
  • Lilian T. L. Costallat
    • 2
  1. 1.McGill UniversityMontrealCanada
  2. 2.Rheumatology Unit, Department of Internal MedicineState University of CampinasCampinasBrazil
  3. 3.Disciplina de Reumatologia, Departamento de Clínica Médica Faculdade de Ciências MédicasUniversidade Estadual de Campinas (UNICAMP) Distrito de Barão GeraldoCampinas-SPBrazil

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