Somers EC et al. (2005) Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 52: 2761–2767

Depot leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analogue, protects against premature ovarian failure (POF) in women receiving cyclophosphamide for systemic lupus erythematosus (SLE), a recent trial has found.

SLE affects a disproportionately large number of women of child-bearing age, but severe manifestations of SLE are often treated with cyclophosphamide, a drug associated with significant toxicities including POF. Continuous administration of a GnRH analogue suppresses ovulation and reduces estrogen and progesterone to prepubertal levels, and has been shown in animal and pilot human studies to prevent chemotherapy-induced ovarian damage.

In this latest trial, 40 women under the age of 35 years were enrolled: 39 with severe SLE and one with systemic vasculitis. All participants were treated with monthly intravenous cyclophosphamide plus a tapering dosage of daily oral prednisone. In 20 women, a GnRH analogue injection was also given 10 days prior to cyclophosphamide, although some women did not receive this until the second monthly cycle. The remaining 20 women were age-matched and cyclophosphamide-dose-matched controls.

Results showed that the GnRH analogue significantly reduced POF compared to the control treatment. The GnRH analogue was generally well tolerated, although two patients developed thrombocytopenia and experienced severe dysfunctional bleeding.

Further investigations are needed to confirm the efficacy and mechanism of the ovarian protection, but GnRH-analogue injection has the potential to be a safe, cost-effective, easily administered method for ovarian preservation in women undergoing chemotherapy for various indications.