Ovarian failure in oral cyclophosphamide treatment for systemic lupus erythematosus

Abstract

Ninety-two women with systemic lupus erythematosus treated with oral cyclophosphamide were studied to ascertain the prevalence and the factors associated with ovarian dysfunction. Menstrual disturbance during treatment occurred in 55% of patients: 36% had amenorrhoea and 19% had oligomenorrhoea. Sustained oligomenorrhoea occurred in 12% patients. Permanent amenorrhoea (> 12 months) after cessation of oral cyclophosphamide occurred in 27% of patients. Hormonal studies in these patients were consistent with ovarian failure. Older age at initiation of treatment and high cumulative dose of cyclophosphamide were found to be associated with this outcome. There was a trend towards linear relationship between the age of initiation of cyclophosphamide therapy and frequency of amenorrhoea. A statistically significant association between amenorrhoea and cumulative dose of cyclophosphamide after adjustment for age was found whereas no such association was linked to the duration of treatment. Fourteen of the 23 women who wished to become pregnant after cessation of treatment conceived resulting in 20 live births and two abortions.

Keywords

Systemic lupus erythematosus Cyclophosphamide Amenorrhoea

Get full access to this article

View all access options for this article.

References

Steinberg AD , Steinberg SC Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisolone only. Arthritis Rheum 1991; 34: 945-50.

Chapman RM , Sutcliff SB , Malpass JS Cytotoxic-induced ovarian failure in women with Hodgkin's disease. I. Hormone function. JAMA 1979; 242: 1171-81.

Chapman RM Effect of cytotoxic therapy on sexuality and gonadal function. Semin Oncol 1982; 9: 84-94.

Fries JF , Sharp GC , McDevitt H. , Holman HR Cyclophosphamide therapy in connective tissue disease. Clin Res 1970; 18: 134 (abstract).

Warne GL , Fairley KF , Hobbs JB , Martin Fir. Cyclophosphamide-induced ovarian failure. New Engl J Med 1973; 289: 1159-62.

Kumar R. , Biggart JD , McEvoy J. , McGeown MC Cyclophosphamide and reproductive function. Lancet 1972; 1: 1212-14.

Uldall PR , Kerr Dns , Tacchi D. Sterility in cyclophosphamide. Lancet 1972 ; 1: 693-4.

Linssen WH , Notermans NC , Hommes OR , Rolland R. Amenorrhoea after immunosuppressive treatment of multiple sclerosis. Acta Neurol Scand 1987; 76: 204-9.

Boumpas DT , Austin HA , Vaughan EM , Yarboro CH , Klippel JH , Balow JE Risk for sustained amenorrhoea in patients with systemic lupus erythematosus receiving intermittent cyclophosphamide therapy. Ann Intern Med 1993; 119: 366-9.

10.

Ataya KM , Moohissi K. Chemotherapy-induced premature ovarian failure: mechanism and prevention. Steroids 1989; 54: 607-26.

11.

Ataya KM , Valerote FA , Ramachi-Ataya AJ Effects of cyclophosphamide on immature rat ovary. Cancer Res 1989; 49: 1660-4.

12.

Miller JJ , Williams GF , Leissring JC Multiple late complications of therapy with cyclophosphamide inducing ovarian destruction. Am J Med 1971; 50: 530-2.