Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO-Study

Autoimmun Rev. 2006 Apr;5(4):269-72. doi: 10.1016/j.autrev.2005.10.001. Epub 2005 Oct 27.

Abstract

Background: With dramatically improved survival rates of SLE patients, comorbidity and long-term damage such as premature ovarian failure (POF) gain increasing importance. In the Erlangen cohort, 14% of cyclophosphamide treated patients younger than 41 years have POF, which is a common consequence of cyclophosphamide treatment.

Patients and methods: We tested the concentrations of FSH and LH, before, during and after cyclophosphamide treatment in 63 premenopausal women with SLE without ovarian protection and initiated the PREGO-Study (Prospective randomized study on protection against gonadal toxicity) in patients with SLE.

Results: In lupus patients treated with cyclophosphamide, 60% suffered from POF and hypergonadotropic amenorrhea. Whereas the POF rate was <50% in women below 30 years, it was 60% between 30 and 40 years. The cumulative dosage of cyclophosphamide also strongly influenced POF rate.

Conclusions: Our present results, with a high POF rate in Cyclophosphamide treated SLE patients demonstrate the urgent need for ovarian protection in this patient group. Besides POF these women are at high risk for premature atherosclerosis which is the major cause of death in lupus. Following preliminary encouraging experience in women with lymphoma, in whom the temporary induction of a prepubertal hormonal milieu during chemotherapy, has significantly decreased the risk of POF, we have initiated the PREGO-Study, comparing randomised monthly injection versus no injection of gonadotropin-releasing hormone analogue (GnRH-a) to young SLE patients during cyclophosphamide therapy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cohort Studies
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / therapeutic use
  • Female
  • Fertility Agents, Female / therapeutic use*
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Luteinizing Hormone / blood
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / chemically induced*
  • Primary Ovarian Insufficiency / prevention & control*
  • Prospective Studies

Substances

  • Fertility Agents, Female
  • Immunosuppressive Agents
  • Gonadotropin-Releasing Hormone
  • Cyclophosphamide
  • Luteinizing Hormone
  • Follicle Stimulating Hormone