High Doses of Triptorelin Protect Ovaries, Are Safe for Young Female SLE Patients

Inducing ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) is protective against ovarian failure from treatment with cyclophophamide. A clinical trial from Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine has established a safe dose of triptorelin that effectively achieves and maintains complete ovarian suppression in females younger than 21 years of age with SLE.

Although cyclophosphamide is a commonly prescribed treatment for patients with childhood-onset SLE and organ damage, it is known to be gonadotoxic. Depending on the age of the patient at the start of therapy, ovarian failure occurs at a rate of less than 50% in females younger than 30 years old and a rate of 60% in females between 30 and 40 years old.

To prevent ovarian failure, it can be beneficial to administer a gonadotropin-releasing hormone such as triptorelin to induce ovarian suppression before treatment with cyclophosphamide and preserve ovarian function. However, these previous studies have been in older women and are not representative of the effects of triptorelin on younger women. To determine a safe dose and see how long one must wait to have a protective effect, researchers in Cincinnati conducted a multicenter clinical trial, “Triptorelin for Ovary Protection in Childhood Onset Lupus,” in collaboration with treatment centers across the United States and Watson Pharmaceuticals.

In total, 25 patients completed the trial. Treatment consisted of a 24-week cyclophosphamide induction therapy that required an intramuscular injection of triptorelin or placebo every four weeks. After this phase, patients received cyclophophamide every 6-12 weeks. Four different treatment groups were used, with each administering a different dose of triptorelin.

“Treatment with triptorelin at a weight-adjusted dose of 120 micrograms/kilogram body weight provided sustained complete ovarian suppression in 90% of the patients,” stated Hermine I. Brunner, MD, first author on the writeup of results found in “Randomized, Double-Blind, Dose-Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset Systemic Lupus Erythematosus,” which was published in Arthritis and Rheumatology. “After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression.”

Although the effective doses of triptorelin are considered high, they were well tolerated by patients. Administering these doses of triptorelin at least 22 days before treatment with cyclophosphamide therapy may be the best regimen for inducing ovarian protection in young females with SLE who are to be treated with cyclophosphamide.