Effect of age, menopause and cyclophosphamide use on damage accrual in systemic lupus erythematosus patients from LUMINA, a multiethnic US cohort (LUMINA LXIII)

Abstract

Sir -The prognosis and survival rates of patients with systemic lupus erythematosus (SLE) have improved over the years1; thus, an increasing number of women with SLE are reaching the age of menopause. In addition, the use of cyclophosphamide therapy and the disease itself increase the risk of premature ovarian failure in these patients.2 Therefore, as our LUMINA (Lupus in Minorities: Nature versus Nurture) cohort matures, we have been intrigued by the accrual of damage in our postmenopausal women. Previously, we have examined damage accrual in our cohort patients whose disease started before and after the menopause and concluded that it was age rather than the menopause that accounted for damage accrual in the postmenopausal women.3 With a larger number of LUMINA cohort patients, and more years of observation having occurred, we sought to re-examine this matter. We, therefore, examined the role of menopause versus age by regressing age on menopause so that the effect of menopause per se could be better determined.The current analyses were limited to the women in the LUMINA cohort. Briefly, at entry into the cohort (T0), patients had disease duration ≤5 years, were ≥16 years of age and were of defined ethnicity (Hispanic from Texas and Puerto Rico, African American, or Caucasian).

Cyclophosphamide Administration Routine in Autoimmune Rheumatic Diseases: A Review

“…45 and cardiovascular failure due to cyclophosphamide cardiotoxicity. 36 Other adverse reactions from cyclophosphamide are amenorrhea, 18 early menopause, 46 and hair loss. 3 …”

“…55,60 Thus, the administration of dexamethasone should be started in the morning, 30 min before the administration of cyclophosphamide, preferably at 7:30 a.m. 58 After the emesis caused by cyclophosphamide was classified as a delayed-type, 56 and in view of the decrease of cyclophosphamide efficacy when ondansetron is administered prior to this chemotherapeutic agent, ondansetron (8 mg PO 31,61 administered at 6 and 14 or 8 and 16 h post-ChT, and with a maximum dose of 16 mg after chemotherapy, not exceeding 32 mg per day) was the last drug used for the prophylaxis of emesis caused by cyclophosphamide. 31 Other important adverse effects of cyclophosphamide include hematologic toxicity, 18 kidney failure, 20 hyponatremia, 45,62 neurological impairment, 45 amenorrhea, 18 early menopause, 46 hair loss, 3 hepatotoxicity (rare), 3 and late-onset cancer. 18 The dose of cyclophosphamide for the treatment of systemic lupus erythematosus, including those patients with neuropsychiatric and/or hematologic disorders, with class IV lupus nephritis, and with other serious manifestations of systemic lupus erythematosus, is 0.5-1 g/m 2 IV monthly, 5,62 with dosage adjustment in patients with hematological toxicity and kidney failure.…”

“…46 A decrease in gonadal function was found, and gonadal failure was defined as the occurrence of amenorrhea for more than six months without a history of hysterectomy. 46 Cyclophosphamide has also been associated with teratogenicity. 18 As to cyclophosphamide dose adjustment in patients with kidney failure, this is only done in severe cases, that is, with a creatinine clearance <10 mL/min.…”

“…36 Other adverse reactions caused by cyclophosphamide include amenorrhea, menopause, and late-onset cancer, including esophageal, lung and bladder adenocarcinoma. 18,46 Cyclophosphamide was administered at a dose of 750-1000 mg/m 2 body surface in LUMINA (Lupus in minorities, nature versus nurture), a multicenter study performed including 567 women aged under 51 years. 46 A decrease in gonadal function was found, and gonadal failure was defined as the occurrence of amenorrhea for more than six months without a history of hysterectomy.…”

“…18,46 Cyclophosphamide was administered at a dose of 750-1000 mg/m 2 body surface in LUMINA (Lupus in minorities, nature versus nurture), a multicenter study performed including 567 women aged under 51 years. 46 A decrease in gonadal function was found, and gonadal failure was defined as the occurrence of amenorrhea for more than six months without a history of hysterectomy. 46 Cyclophosphamide has also been associated with teratogenicity.…”