Menstrual Disorders in Girls With Systemic Lupus Erythematosus Treated With Cyclophosphamide

Gonzalez-Crespo, Maria R.; Gómez-Reino, Juan J.; Merino, Ramón; Ciruelo, E.; Gómez-Reino, F; Muley, Rafael; García-Consuegra, Julia; Pinillos, Valvanera; Rodríguez‐Valverde, V.

doi:10.1093/rheumatology/34.8.737

Cited by 34 publications

(23 citation statements)

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“…Amenorrhea was reported in 26% of female SLE patients younger than 40 years old who were treated with intravenous CYC pulses (33). In juvenile SLE, we have previously encountered absence of ovary toxicity with intravenous CYC pulses, but a 50% rate of amenorrhea with oral CYC, owing perhaps to the larger total dose used (34). Taken together, the above findings provide evidence against the use of oral CYC in SLE patients with nephritis.…”

Section: Discussionmentioning

confidence: 85%

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Ciruelo

Cruz

López

et al. 1996

Arthritis & Rheumatism

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Objective. To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables.Methods. This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter a t 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors.ResuZts. Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by Renal disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) (1-4). The use of immunosuppressive agents has been associated with a better prognosis (5-12). Combined cyclophosphamide (CYC) and glucocorticoid therapy is deemed to yield significant improvement in renal survival (13-15) and positive economic impact, compared with glucocorticoid therapy alone (16). However, several questions regarding the use of CYC in lupus nephritis remain unresolved. The optimum dosage, length of therapy, and method of administration have not been fully established. Toxicity and side effects are major limiting factors.The rate of relapse of nephritis following CYC therapy is largely unknown. This issue is important because recurrent episodes of nephritis may lead to progressive renal failure. In various studies, the rate of relapse of nephritis has ranged between 0 and 50%. However, followup of patients in these studies was short or was not mentioned in the reports (11,13,(17)(18)(19). Boumpas et a1 (20) and found that short courses of intravenous CYC pulses were associated with a higher rate of disease exacerbation than were longer courses. Information regarding the influence of demographic and clinical variables, renal histology, and methods of CYC administration is lack-

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Section: Discussionmentioning

confidence: 85%

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Ciruelo

Cruz

López

et al. 1996

Arthritis & Rheumatism

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“…Although the toxic effects of cyclophosphamide on ovarian function have been observed since the 1960s in patients with rheumatoid arthritis using oral cyclophosphamide (24), many issues pertaining to gonadal insufficiency in patients with SLE remain unexplained to this day. There are very few articles in the medical literature that deal with these issues (3)(4)(5)(6)(7)(8)(12)(13)(14)(25)(26)(27), and the majority focus on the incidence of ovarian failure after cyclophosphamide use.…”

Section: Discussionmentioning

confidence: 99%

“…The main factors which have been associated with the onset of ovarian failure in patients diagnosed with SLE are disease activity (1), anti-ovarian antibodies (2,3), cytotoxic agents (4)(5)(6)(7)(8) and, more recently, use of thalidomide (9,10). Other potential causes of ovarian insufficiency not specific for lupus are polyglandular insufficiency, viral infections, smoking, oophorectomy, emotional disorders, and idiopathic origin (11).…”

Section: Introductionmentioning

confidence: 99%

“…Gonadal toxicity should be of great concern in premenopausal women who take cyclophosphamide. The frequency of ovarian insufficiency in SLE patients treated with this drug ranges from 11 to 59% in different studies and depends on the dose used, the age of the patient and methodological differences (4)(5)(6)(7)(8)(12)(13)(14). Since estrogens have biological effects which protect the cardiovascular system, as well as the skeletal system from bone loss, estrogen deficiency is linked with a greater risk for cardiovascular disease (15) and osteoporosis (16), thus contributing to higher morbidity and mortality among patients diagnosed with lupus.…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for ovarian failure in patients with systemic lupus erythematosus

Medeiros

Silveira

Menezes

et al. 2001

Braz J Med Biol Res

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The aim of the present study was to identify the risk factors for ovarian failure in patients with systemic lupus erythematosus. Seventy-one women aged 17 to 45 years with systemic lupus erythematosus were studied. Patients were interviewed and their medical records reviewed. Demographic characteristics, clinical and serologic profiles, and menstrual and obstetric histories were recorded. Disease activity was measured by the systemic lupus erythematosus disease activity index. Serum FSH, LH, estradiol, progesterone, TSH, prolactin, and antimicrosomal and antithyroglobulin antibodies were measured. Patients who developed ovarian failure were compared to those who did not. Ovarian failure occurred in 11 patients (15.5%) and nine had premature menopause (11.3%). Cyclophosphamide administration and older patient age were found to be associated with ovarian failure. The cumulative cyclophosphamide dose was significantly higher in patients with ovarian failure than in those without this condition (18.9 vs 9.1 g; P = 0.04). The relative risk for ovarian failure in patients with cumulative cyclophosphamide dose higher than 10 g was 3.2. TSH levels were high in 100% of patients with ovarian failure who had received pulse cyclophosphamide. Ovarian failure, and premature menopause in particular, is common in patients with systemic lupus erythematosus, with the most important risk factors being cyclophosphamide dose and age. Thyroid problems may be another risk factor for ovarian failure in patients with lupus.

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“…There was also a higher risk of patients having an irregular cycle after cyclophosphamide (CTX) therapy, as this therapy is known to damage ovarian follicles. 3,4 However, it is currently unknown whether SLE women with or without alkylating therapy who have normal menstruation would have impaired ovarian reserve compared to healthy women. Therefore, in this study we assessed ovarian reserve in SLE patients with a normal menstrual cycle.…”

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confidence: 99%

Subclinical Impairment of Ovarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstruation Not Using Alkylating Therapy

Zhan

Liang

et al. 2013

Journal of Women's Health

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Background: Disease activity is a major factor in menstrual disorders in systemic lupus erythematosus (SLE) patients not receiving alkylating therapy. However, the ovarian reserve of SLE women with normal menstruation is still unclear. Methods: Twenty-three SLE patients naïve to cytotoxic agents (SLE group) and nineteen SLE patients receiving current or previous cyclophosphamide (CTX) therapy (without other cytotoxic agents; SLE-CTX group) were enrolled. Twenty-one age-matched healthy women served as controls. All patients and controls had a regular menstrual cycle. Basal hormone levels, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), and anti-Mü llerian hormone (AMH), and antral follicle count (AFC) were analyzed in the two study groups and compared with the control group. Results: No significant differences were found between the SLE, SLE-CTX, and control groups in age, body mass index (BMI), and basal FSH and LH levels. The E 2 (P = 0.023) levels were high and the AMH (P = 0.000) values and AFC (P = 0.001) were significantly lower in the SLE and SLE-CTX groups compared to control. However, these values were similar between the SLE and SLE-CTX groups. Conclusion: SLE patients not receiving alkylating therapy who had normal menstruation and short illness duration still had an impaired ovarian reserve.

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Menstrual Disorders in Girls With Systemic Lupus Erythematosus Treated With Cyclophosphamide

Cited by 34 publications

References 0 publications

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide

Risk factors for ovarian failure in patients with systemic lupus erythematosus

Subclinical Impairment of Ovarian Reserve in Systemic Lupus Erythematosus Patients with Normal Menstruation Not Using Alkylating Therapy

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