PROLONGED GONADOTROPIN-RELEASING-HORMONE AGONIST TREATMENT OF SYMPTOMATIC ENDOMETRIOSIS - THE ROLE OF CYCLIC SODIUM ETIDRONATE AND LOW-DOSE NORETHINDRONE ADD-BACK THERAPY

Objective: To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis. Design: Prospective randomized open label study. Setting: Tertiary care university-affiliate reproductive medicine program. Patients: Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis. Interventions: All patients received a depot preparation of the GnRH a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III Volunteers (n = 18) were untreated and followed for bone density changes. Main Outcome Measures: Disease extent at follow up laparoscopy; pain, vasomotor, and vaginal symptom scores; hone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge. Results: Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group IH untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A, levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II. Conclusions: The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy achieved.