Therapy Insight: preserving fertility in cyclophosphamide-treated patients with rheumatic disease

Cyclophosphamide remains a necessary treatment for severe rheumatic diseases, despite the continued search for alternative therapies with less gonadal toxicity. The risk of premature gonadal failure and sterility might lead young patients to delay treatment with cyclophosphamide. The patient's age at treatment and the cumulative dose received remain important risk factors for cyclophosphamide-induced gonadal failure in both males and females. Estrogen-containing oral contraceptives for females and testosterone for males are suggested to reduce the gonadal toxicity of cyclophosphamide, although few studies support these interventions. Owing to increased side effects, hormonal therapy is often avoided in patients with edema, hypertension, nephrotic syndrome or antiphospholipid antibodies. Agonists and antagonists of gonadotropin receptors are under study. Gonadotropin-receptor agonists might have beneficial effects in addition to suppression of sex-hormone production. The outcome of attempted cryopreservation of eggs, embryos or ovaries remains uncertain for women seeking to preserve their reproductive potential. Storing male gametes before chemotherapy is widely practiced and technically successful. As recovery of menses or production of testosterone does not predict individual fertility, identification of biomarkers of gonadal function and reserve, including serum levels of several hormones, ultrasonographic measurements of ovarian volume and antral follicle count, are necessary.