Risk factors for ovarian failure in patients with systemic lupus erythematosus

Abstract

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.

Clinical trial: cyclophosphamide pulse therapy – a promising therapeutic alternative in refractory Crohn’s disease

“…In pulsed cyclophosphamide-treated vasculitis patients, ovarial insufficiency varied between 15.5% and 27.4% and was found to be dose-dependent. 29,30 Of note, although less toxic, the pulse regime was equally effective in induction of remission. These data are critical to the rationale to apply the pulse treatment of cyclophosphamide for CD patients with severe flares.…”

Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study

“…Studies have reported ovarian insufficiency in 10-83 % of female SLE patients treated with CYC, depending primarily on the subject's age at initiation of treatment and cumulative CYC dose [25][26][27]. Medeiros et al showed that SLE patients treated with a cumulative CYC dose of greater than 10 g had a 3.2 times higher risk of developing ovarian insufficiency than patients receiving a cumulative dose lower than 10 g [28]. Our results showed that 28.6 % of patients with premature cessation of menses following high-dose CYC were consistent with previous reports.…”

Nonmalignant Diseases and Treatments Associated with Primary Ovarian Failure: An Expanded Role for Fertility Preservation

“…10 Severe manifestations of SLE, such as lupus nephritis, are often treated with cyclophosphamide, which greatly improves the prognosis in these patients. [11][12][13] However, cyclophosphamide is an alkylating chemotherapeutic agent known to cause POI. 6 The incidence of amenorrhea following cyclophosphamide treatment for SLE ranges from 27% to 60%, with 80% of these patients experiencing sustained amenorrhea for longer than 1 year, as noted by elevated gonadotropin levels.…”

“…6 The incidence of amenorrhea following cyclophosphamide treatment for SLE ranges from 27% to 60%, with 80% of these patients experiencing sustained amenorrhea for longer than 1 year, as noted by elevated gonadotropin levels. 6,[9][10][11]14,15 The Euro-Lupus protocol of cyclophosphamide therapy (500 mg given every 2 weeks for six doses of 500 mg cyclophosphamide) has not been associated to date with infertility. 16 The exact cyclophosphamide dose that causes POI is not known; Ioannidis et al 17 showed that in women > 32 years of age, 50% experienced amenorrhea at 8 g/m 2 and 90% experienced it at 12 g/m 2 .…”

“…19,21 Risk factors for POI secondary to cyclophosphamide therapy include age, cumulative dose, history of thyroid disease, disease duration, and the presence of anti-Ro and anti-U1RNP antibodies. 6,[10][11][12][13][14][15]17,22 Cytochrome P450 polymorphisms among patients with SLE can also explain the range of ovarian function after cyclophosphamide exposure. In retrospective analyses, the presence of the CYP2C19*2 polymorphism variant allele was associated with a lower risk of ovarian toxicity from cyclophosphamide exposure.…”