Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1996 Apr;55(4):224–229. doi: 10.1136/ard.55.4.224

Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide.

E M McDermott 1, R J Powell 1
PMCID: PMC1010142  PMID: 8733438

Abstract

OBJECTIVE: To investigate the incidence of ovarian failure after pulse cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare this with two control groups: SLE patients treated with azathioprine, and a healthy age matched population. METHODS: All women patients with SLE treated with pulse cyclophosphamide in our department were identified and questioned concerning menstrual history. All the hospital notes were reviewed and details recorded on dose of cyclophosphamide, duration of treatment, side effects and lowest pretreatment neutrophil and leucocyte counts during the course of treatment. Disease controls were recruited from our department and healthy controls from the local family health services authority (FHSA) register. RESULTS: Incidence of ovarian failure in the premenopausal cyclophosphamide treated group was 54% and the incidence of premature menopause (occurring before age 40 years) was 41%. Increasing age at start of treatment showed a linear trend with incidence of ovarian failure (p = 0.01). Using logistic regression, increasing duration of treatment was related to incidence of ovarian failure (p = 0.047 in those treated age 35 years or younger). An association between the lowest neutrophil count throughout the treatment period, when taken immediately before each planned cyclophosphamide pulse, and the incidence of ovarian failure was also demonstrated (p = 0.04 in those treated before age 40 years). CONCLUSION: Ovarian failure--in particular, premature failure after treatment with pulse cyclophosphamide--is common. Factors associated with increased risk include greater age at start of treatment, longer period of treatment, and greater degree of marrow suppression as assessed by the neutrophil count immediately before each planned cyclophosphamide pulse.

Full text

PDF
224

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ataya K. M., McKanna J. A., Weintraub A. M., Clark M. R., LeMaire W. J. A luteinizing hormone-releasing hormone agonist for the prevention of chemotherapy-induced ovarian follicular loss in rats. Cancer Res. 1985 Aug;45(8):3651–3656. [PubMed] [Google Scholar]
  2. Ataya K., Moghissi K. Chemotherapy-induced premature ovarian failure: mechanisms and prevention. Steroids. 1989 Dec;54(6):607–626. doi: 10.1016/0039-128x(89)90084-6. [DOI] [PubMed] [Google Scholar]
  3. Austin H. A., 3rd, Klippel J. H., Balow J. E., le Riche N. G., Steinberg A. D., Plotz P. H., Decker J. L. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med. 1986 Mar 6;314(10):614–619. doi: 10.1056/NEJM198603063141004. [DOI] [PubMed] [Google Scholar]
  4. Boumpas D. T., Austin H. A., 3rd, Vaughan E. M., Yarboro C. H., Klippel J. H., Balow J. E. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med. 1993 Sep 1;119(5):366–369. doi: 10.7326/0003-4819-119-5-199309010-00003. [DOI] [PubMed] [Google Scholar]
  5. Brambilla D. J., McKinlay S. M. A prospective study of factors affecting age at menopause. J Clin Epidemiol. 1989;42(11):1031–1039. doi: 10.1016/0895-4356(89)90044-9. [DOI] [PubMed] [Google Scholar]
  6. Chapman R. M., Sutcliffe S. B. Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease. Blood. 1981 Oct;58(4):849–851. [PubMed] [Google Scholar]
  7. Chrisp P., Goa K. L. Goserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions. Drugs. 1991 Feb;41(2):254–288. doi: 10.2165/00003495-199141020-00008. [DOI] [PubMed] [Google Scholar]
  8. Clayton P. E., Shalet S. M., Price D. A. Gonadal function after chemotherapy and irradiation for childhood malignancies. Horm Res. 1988;30(2-3):104–110. doi: 10.1159/000181039. [DOI] [PubMed] [Google Scholar]
  9. Clements P. J., Davis J. Cytotoxic drugs: their clinical application to the rheumatic diseases. Semin Arthritis Rheum. 1986 May;15(4):231–254. doi: 10.1016/0049-0172(86)90020-x. [DOI] [PubMed] [Google Scholar]
  10. Decker J. L., Klippel J. H., Plotz P. H., Steinberg A. D. Cyclophosphamide or azathioprine in lupus glomerulonephritis. A controlled trial: results at 28 months. Ann Intern Med. 1975 Nov;83(5):606–615. doi: 10.7326/0003-4819-83-5-606. [DOI] [PubMed] [Google Scholar]
  11. Fox D. A., McCune W. J. Immunosuppressive drug therapy of systemic lupus erythematosus. Rheum Dis Clin North Am. 1994 Feb;20(1):265–299. [PubMed] [Google Scholar]
  12. Hopkinson N. D., Doherty M., Powell R. J. The prevalence and incidence of systemic lupus erythematosus in Nottingham, UK, 1989-1990. Br J Rheumatol. 1993 Feb;32(2):110–115. doi: 10.1093/rheumatology/32.2.110. [DOI] [PubMed] [Google Scholar]
  13. Koyama H., Wada T., Nishizawa Y., Iwanaga T., Aoki Y. Cyclophosphamide-induced ovarian failure and its therapeutic significance in patients with breast cancer. Cancer. 1977 Apr;39(4):1403–1409. doi: 10.1002/1097-0142(197704)39:4<1403::aid-cncr2820390408>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  14. Lee S. J., Lenton E. A., Sexton L., Cooke I. D. The effect of age on the cyclical patterns of plasma LH, FSH, oestradiol and progesterone in women with regular menstrual cycles. Hum Reprod. 1988 Oct;3(7):851–855. doi: 10.1093/oxfordjournals.humrep.a136796. [DOI] [PubMed] [Google Scholar]
  15. Luqmani R. A., Palmer R. G., Bacon P. A. Azathioprine, cyclophosphamide and chlorambucil. Baillieres Clin Rheumatol. 1990 Dec;4(3):595–619. doi: 10.1016/s0950-3579(05)80009-3. [DOI] [PubMed] [Google Scholar]
  16. Mattison D. R. The effects of smoking on fertility from gametogenesis to implantation. Environ Res. 1982 Aug;28(2):410–433. doi: 10.1016/0013-9351(82)90139-6. [DOI] [PubMed] [Google Scholar]
  17. Miller R. M., Frank R. A. Zoladex (goserelin) in the treatment of benign gynaecological disorders: an overview of safety and efficacy. Br J Obstet Gynaecol. 1992 Feb;99 (Suppl 7):37–41. doi: 10.1111/j.1471-0528.1992.tb13539.x. [DOI] [PubMed] [Google Scholar]
  18. Miyagawa S., Shirai T., Shimamoto I., Ichijo M., Ueki H. Worsening of systemic lupus erythematosus-associated thrombocytopenia after administration of gonadotropin-releasing hormone analog. Arthritis Rheum. 1994 Nov;37(11):1708–1709. doi: 10.1002/art.1780371123. [DOI] [PubMed] [Google Scholar]
  19. Montz F. J., Wolff A. J., Gambone J. C. Gonadal protection and fecundity rates in cyclophosphamide-treated rats. Cancer Res. 1991 Apr 15;51(8):2124–2126. [PubMed] [Google Scholar]
  20. Richardson S. J. The biological basis of the menopause. Baillieres Clin Endocrinol Metab. 1993 Jan;7(1):1–16. doi: 10.1016/s0950-351x(05)80267-8. [DOI] [PubMed] [Google Scholar]
  21. Roubenoff R., Hoyt J., Petri M., Hochberg M. C., Hellmann D. B. Effects of antiinflammatory and immunosuppressive drugs on pregnancy and fertility. Semin Arthritis Rheum. 1988 Nov;18(2):88–110. doi: 10.1016/0049-0172(88)90002-9. [DOI] [PubMed] [Google Scholar]
  22. Sanders J. E., Buckner C. D., Amos D., Levy W., Appelbaum F. R., Doney K., Storb R., Sullivan K. M., Witherspoon R. P., Thomas E. D. Ovarian function following marrow transplantation for aplastic anemia or leukemia. J Clin Oncol. 1988 May;6(5):813–818. doi: 10.1200/JCO.1988.6.5.813. [DOI] [PubMed] [Google Scholar]
  23. Stanford J. L., Hartge P., Brinton L. A., Hoover R. N., Brookmeyer R. Factors influencing the age at natural menopause. J Chronic Dis. 1987;40(11):995–1002. doi: 10.1016/0021-9681(87)90113-5. [DOI] [PubMed] [Google Scholar]
  24. Steinberg A. D., Decker J. L. A double-blind controlled trial comparing cyclophosphamide, azathioprine and placebo in the treatment of lupus glomerulonephritis. Arthritis Rheum. 1974 Nov-Dec;17(6):923–937. doi: 10.1002/art.1780170602. [DOI] [PubMed] [Google Scholar]
  25. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  26. Uldall P. R., Kerr D. N., Tacchi D. Sterility and cyclophosphamide. Lancet. 1972 Mar 25;1(7752):693–694. doi: 10.1016/s0140-6736(72)90502-8. [DOI] [PubMed] [Google Scholar]
  27. Wang C. L., Wang F., Bosco J. J. Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus. Lupus. 1995 Feb;4(1):11–14. doi: 10.1177/096120339500400103. [DOI] [PubMed] [Google Scholar]
  28. Warne G. L., Fairley K. F., Hobbs J. B., Martin F. I. Cyclophosphamide-induced ovarian failure. N Engl J Med. 1973 Nov 29;289(22):1159–1162. doi: 10.1056/NEJM197311292892202. [DOI] [PubMed] [Google Scholar]
  29. Whelan E. A., Sandler D. P., McConnaughey D. R., Weinberg C. R. Menstrual and reproductive characteristics and age at natural menopause. Am J Epidemiol. 1990 Apr;131(4):625–632. doi: 10.1093/oxfordjournals.aje.a115546. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES