Subcutaneous Administration of a Depot Gonadotropin-Releasing Hormone Agonist Induces Profound Reproductive Axis Suppression in Women

Objective: To compare the IM and SC routes of depot GnRH agonist administration. Design: Prospective, controlled pharmacokinetics study. Setting: Volunteers in an academic research environment. Patient(s): Forty women with benign gynecologic disorders. Intervention(s): Triptorelin administration (3.75 mg) at 28-day intervals for 6 consecutive months. Twenty patients were treated with IM triptorelin, and 20 patients were treated with SC triptorelin. Main Outcome Measure(s): Assessment of 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 increased significantly in the SC group. Plasma triptorelin levels were significantly higher in the IM group in the first month of treatment; thereafter, the pattern reversed, with a nonsignificant trend toward higher 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 months after the last depot triptorelin injection), triptorelin was still measurable and gonadotropins and gonadal steroids were still suppressed. Spontaneous menses returned significantly later in the SC group than in the IM group. Conclusion(s): Subcutaneous triptorelin can be administered by the patient. Both IM and SC triptorelin administration are clinically effective, but they result in different triptorelin pharmacokinetics. Subcutaneous triptorelin is associated with more prolonged amenorrhea than is IM triptorelin, suggesting enhanced pituitary-ovarian suppression. These results suggest that SC triptorelin may allow lower drug dosage administration and/or longer administration intervals.