***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: OBJECTIVE Cyclophosphamide ( CYC ) therapy for systemic lupus erythematosus ( SLE ) , a disease predominantly affecting women of childbearing age , causes an unacceptably high incidence of irreversible premature ovarian failure ( POF ) . This study was performed to evaluate the effectiveness of depot leuprolide acetate , a synthetic gonadotropin-releasing hormone analog ( GnRH-a ) , for protection against POF during CYC therapy . METHODS Young women with severe SLE treated in a st and ardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a ( depot leuprolide acetate ; a 3.75-mg monthly injection during the st and ard CYC regimen ) . Patients treated with GnRH-a were compared with controls individually matched by age ( + /-5 years ) and by cumulative CYC dose ( + /-5 gm ) . Reproductive status was determined after a minimum followup of 3 years after CYC therapy . The primary outcome was time to POF . Paired summary statistical analyses , Kaplan-Meier survival estimates , and Cox regression analyses were performed to assess differences in outcome between groups . RESULTS POF developed in 1 of 20 women treated with GnRH-a ( 5 % ) compared with 6 of 20 controls ( 30 % ) matched by age and cumulative CYC dose ( matched odds ratio 0.09 , P < 0.05 ) . Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a-treated group ( P = 0.04 ) . CONCLUSION Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE To study the ovarian toxicity associated with cyclophosphamide in girls with systemic lupus erythematosus ( SLE ) , we retrospectively review ed the charts of 30 SLE girls aged 16 yr or younger at diagnosis , followed at three university hospitals . Gynaecological history was extracted from the charts or obtained prospect ively . Ten had not received cyclophosphamide therapy , six were treated with daily oral cyclophosphamide , 10 with intravenous pulses and four with daily oral and intravenous pulses . Median oral cyclophosphamide dose was 38 g ( inter-quartile range 75 ) and median intravenous dose 12.95 g ( inter-quartile range 6.2 ) . Six girls had oligomenorrhoea ( 20 % ) and one amenorrhoea ( 3 % ) . Two treated with oral cyclophosphamide had oligomenorrhoea ( 33 % ) and one amenorrhoea ( 17 % ) , two treated with both oral and intravenous pulses had oligomenorrhoea ( 50 % ) , and none of those treated with intravenous pulses alone had menstrual disturbances ( 50 % oral vs 0 % intravenous pulses ; P = 0.016 ) . Girls who had menstrual disturbances had received higher doses of cyclophosphamide than those who did not ( medians : 63 vs 15 g ; P < 0.05 ) . In summary , menstrual disturbances in SLE girls treated with cyclophosphamide are related to the total dose and perhaps to the administration method Introduction While the role of mycophenolate mofetil ( MMF ) in the management of lupus nephritis has been increasingly recognized , limited information is available regarding its efficacy and safety as a long-term maintenance treatment . The aim of the present study was to evaluate the efficacy and safety profile of MMF as maintenance therapy for proliferative lupus nephritis . Methods Thirty-three consecutive patients with proliferative lupus nephritis received induction therapy with five to seven monthly intravenous ( iv ) pulses of cyclophosphamide ( CYC ) plus iv steroids followed by oral MMF 2 g/day as maintenance therapy for a median time of 29 months ( range 9 to 71 months ) . Primary end points were the achievement of renal remission , complete renal remission , disease remission - renal and extrarenal - , the occurrence of renal relapse , chronic renal failure and death . Secondary end points were the extrarenal disease activity and drug adverse events . The clinical and laboratory parameters were compared during follow-up by means of nonparametric statistical tests . Time to event analysis was performed according to the Kaplan-Meier method . Results A significant improvement of all renal parameters was observed at the end of the induction treatment and at the latest follow-up compared to baseline . The rate of patients achieving renal remission until the end of follow-up was 73 % , whereas that of complete renal remission was 58 % . The median survival times in the Kaplan-Meier analyses were 7 and 16 months , respectively . Remission was maintained in all but four ( 12 % ) patients who relapsed within 19 to 39 months after initial response . At the end of follow-up , 51 % of the patients had reached disease remission . The median survival time of disease remission was 18 months . Extrarenal manifestations were well controlled in most of the patients . In one patient receiving MMF , extrarenal activity led to treatment discontinuation . Non life-threatening drug adverse events developed in 18 patients ( 58 % ) and included infections , amenorrhea , myelotoxicity , gastrointestinal complications , hypercholesterolemia , alopecia and drug intolerance . None of the patients developed chronic renal insufficiency or died from any cause . Conclusions MMF appeared to be efficacious and safe as maintenance treatment for proliferative lupus nephritis OBJECTIVE To identify predictors of intravenous cyclophosphamide ( IC ) induced sustained amenorrhea , especially in young premenopausal women with systemic lupus erythematosus ( SLE ) . METHODS The cumulative dose result ing in sustained amenorrhea in 50 and 90 % of the treated women ( D50 and D90 ) and predictors of sustained amenorrhea at various ages were determined with Kaplan-Meier plots and Cox regressions in a consecutively enrolled cohort of 67 premenopausal women with SLE who received a pulsed IC regimen ( monthly doses of 0.75 - 1.00 g/m2 ) for nephritis ( n = 59 ) or other indications ( n = 8) . RESULTS Twenty-one of 67 women developed sustained amenorrhea of > 12 months ' duration . Age was the strongest determinant of this adverse event . For women in the upper age tertile ( > or= 32 years old ) , D50 was 8 g/m2 and D90 was 12 g/m2 , and no strong protective or predisposing factors were identified . Conversely , only 5 of 44 women < or= 31 years old at initiation of IC developed sustained amenorrhea . In these young women the risk was modulated by the prior SLE disease duration ( risk increased 1.28-fold per year ; p = 0.002 ) , the presence of anti-U1RNP antibodies ( relative risk 9.5 ; p = 0.016 ) , and the presence of anti-Ro antibodies ( relative risk 13.5 ; p = 0.021 ) . In multivariate modeling , anti-U1RNP and disease duration were still significant ( p < 0.05 ) . CONCLUSION Sustained amenorrhea is difficult to avoid in women 32 years or older , even with very short IC courses , and alternative regimens should be considered . In younger women treated with a monthly IC regimen , sustained amenorrhea may occur predominantly in those with the recognized adverse predictors of this complication CONTEXT Resumption of ovarian activity and spontaneous pregnancies are described in patients with premature ovarian failure ( POF ) , but there is a lack of data concerning the prevalence of and predictive factors for these phenomena . OBJECTIVE The aim of the study was to determine both the prevalence of and predictive factors for spontaneous resumption of ovarian function in POF patients . DESIGN AND SETTING A mixed retrospective and prospect i ve study was performed at a referral center for reproductive endocrinology . PATIENTS A total of 358 consecutive POF patients were followed from 1997 to 2010 in our center . MAIN OUTCOMES MEASURES The cumulative incidence of resumption of ovarian function was determined , and predictive factors were identified by univariate and multivariate analysis . RESULTS Of 358 patients with idiopathic POF , 86 ( 24 % ) patients presented features indicating resumption of ovarian function , and in 77 cases ( 88 % ) within 1 yr of diagnosis . Twenty-one spontaneous pregnancies ( 16 births , five miscarriages ) occurred in 15 ( 4.4 % ) patients . Multivariate analysis ( Cox model ) showed that a familial history of POF , secondary amenorrhea , presence of follicles at ultrasound , and inhibin B and estradiol levels were significantly predictive of resumption of ovarian function ( P < 0.01 ) , whereas association with an autoimmune disease , anti-mullerian hormone level , the presence of follicles on biopsy , and /or genetic abnormalities did not appear predictive . We created a predictive score for resumption of ovarian function comprising age at diagnosis , presence of follicles at ultrasound , and inhibin B level . CONCLUSION Intermittent ovarian activity in patients with POF is not a rare phenomenon . The predictive score described in this study may help us to identify POF patients most likely to recover intermittent ovarian function OBJECTIVE Glomerulonephritis is a severe manifestation of systemic lupus erythematosus ( SLE ) that is usually treated with an extended course of intravenous ( IV ) cyclophosphamide ( CYC ) . Given the side effects of this regimen , we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment , followed by azathioprine ( AZA ) as a remission-maintaining treatment . METHODS In this multicenter , prospect i ve clinical trial ( the Euro-Lupus Nephritis Trial [ ELNT ] ) , we r and omly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen ( 6 monthly pulses and 2 quarterly pulses ; doses increased according to the white blood cell count nadir ) or a low-dose IV CYC regimen ( 6 fortnightly pulses at a fixed dose of 500 mg ) , each of which was followed by AZA . Intent-to-treat analyses were performed . RESULTS Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group . Sixteen percent of those in the low-dose group and 20 % of those in the high-dose group experienced treatment failure ( not statistically significant by Kaplan-Meier analysis ) . Levels of serum creatinine , albumin , C3 , 24-hour urinary protein , and the disease activity scores significantly improved in both groups during the first year of followup . Renal remission was achieved in 71 % of the low-dose group and 54 % of the high-dose group ( not statistically significant ) . Renal flares were noted in 27 % of the low-dose group and 29 % of the high-dose group . Although episodes of severe infection were more than twice as frequent in the high-dose group , the difference was not statistically significant . CONCLUSION The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis , a remission-inducing regimen of low-dose IV CYC ( cumulative dose 3 gm ) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen Background : Premature ovarian failure ( POF ) is a common long-term consequence of chemotherapy . Whereas the cytotoxic-induced damage is reversible in other tissues of rapidly dividing cells such as bone marrow , gastrointestinal tract and thymus , it appears to be progressive and irreversible in the ovary , where the number of germ cells is limited , fixed since the fetal life , and can not be regenerated . The gonadal toxicity of cyclophosphamide is well known . In patients with lupus nephritis , premature ovarian failure ( POF ) was reported in half of all treated women after cyclophosphamide pulse therapy  , affecting 100 % of those older than 30y , about 50 % of the patients between the ages of 20 - 30y and only 13 % of the patients younger than 20y of age . Following our preliminary encouraging experience in women with lymphoma , whereby the temporary induction of a prepubertal hormonal milieu , during chemotherapy , has significantly decreased the risk of POF , we have administered a monthly injection of gonadotropin-releasing hormone agonistic analogue ( GnRH-a ) to eight young women in parallel to alkylating agent chemotherapy .  Material s and methods : A monthly intramuscular depot injection of 3.75 mg D-TRP6-GnRH-a ( Decapeptyl C.R. ) was administered after informed consent to eight women with autoimmune , severe connective tissue diseases ( seven SLE patients and one woman with nephrotic syndrome ) in parallel to chemotherapy  , for up to 
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Conclusion : Sustained amenorrhoea  with IV cyclophosphamide was observed in patients with ARD , especially with increasing age and cumulative doses > 5 g .