risk of ovarian failure in egyptian patients with lupus nephritis treated with various cytotoxic and immunosuppressive drugs

ABSTRACT

To compare the effect of various immuno-suppressive drugs on gonadal function in females with SLE. We studied 128 female patients with SLE, 68 of them had lupus nephritis [LN]. All the patients with LN received corticosteroid [CS] plus one of theses drugs cyclophosphamide [CP] [24 cases], azathioprine [AZA] [1 6 cases], mycophenolate mofetil [MPM] [10 cases] and cyclosporine [CyA] [18 cases]. The other 60 cases received CS alone. Blood samples were taken for inhibin B,esradiol E2, LH and FSH before and six months after starting the treatment. Clomiphene test was done in some cases. Sustained amenorrhea [> 1 year] occurred in 33% of the patients in the CP group and in 5% of patients in the CyA group. After 6 months of treatment, the mean level of inhibin B, LH and FSH -in cases that received CS alone- were lower than their basal values. In the CP group, the mean values of E2 and inhibin B after treatment were lower significantly [p=0.01 and 0.001] while LH, FSH were higher significantly than before treatment after controlling the effect of the associated CS doses. Corticosteroid treatment decreased the cytotoxic effect of CP on the ovaries. In the CyA group the mean levels of inhibin B, FSH hormones were lower significantly than before treatment, in the AZA group and the MPM groups the mean values of the hormones were not different than before treatment. Activity of the disease measured by SLEDAI score [systemic lupus erythematosus activity index score], SLICC/ACR renal damage score [systemic lupus International Collaborating Clinic /Amerlcan College of Rheumatology], had no effect on the occurrence of sustained amenorrhoea Also activity and chronicity renal biopsy index had no effect on ovarian failure in these cases. CP is an effective drug for lupus nephritis but possibility of ovarian failure in the young women is a serious side effect and must be discussed clearly with the patient. Combining large maintenance daily doses of Corticosteroid > 20 mg /day did not affect the initiation of amenorrhoea but reduced the incidence of sustained amenorrhoea after the discontinuation of the treatment. CyA may affect gonadal dysfunction. Other immunosuppressive drugs had a negligible effect on ovarian function. Inhibin B is a sensitive test for detection ovarian dysfunction in these patients