SUBCUTANEOUS ADMINISTRATION OF A DEPOT GONADOTROPIN-RELEASING-HORMONEAGONIST INDUCES PROFOUND REPRODUCTIVE AXIS SUPPRESSION IN WOMEN

Objective: To compare the IM and SC routes of depot GnRH agonist admin istration. Design: Prospective, controlled pharmacokinetics study. Set ting: Volunteers in an academic research environment. Patient(s): Fort y women with benign gynecologic disorders. Intervention(s): Triptoreli n administration (3.75 mg) at 28-day intervals for 6 consecutive month s. Twenty patients were treated with IM triptorelin, and 20 patients w ere treated with SC triptorelin. Main Outcome Measure(s): Assessment o f side effects, GnRH test results, and triptorelin, LH, FSH, estradiol , and progesterone levels. Result(s): The occurrence of injection site redness and itching and of some hypoestrogenic side effects was incre ased significantly in the SC group. Plasma triptorelin levels were sig nificantly higher in the UI group in the first month of treatment; the reafter, the pattern reversed, with a nonsignificant trend toward high er plasma triptorelin levels in the SC group. Serum LH, FSH: estradiol , and progesterone levels were low after the first month of treatment and did not differ between the two treatment groups. On day 196 (2 mon ths after the last depot triptorelin injection), triptorelin was still measurable and gonadotropins and gonadal steroids were still suppress ed. Spontaneous menses returned significantly later in the SC group th an in the IM group. Conclusion(s): Subcutaneous triptorelin can be adm inistered by the patient. Both IM and SC triptorelin administration ar e clinically effective, but they result in different triptorelin pharm acokinetics. Subcutaneous triptorelin is associated with more prolonge d amenorrhea than is LM triptorelin, suggesting enhanced pituitary-ova rian suppression. These results suggest that SC triptorelin may allow lower drug dosage administration and/or longer administration interval s. (C) 1998 by American Society for Reproductive Medicine.