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

Objective: To examine the safety and efficacy of combining cyclic sodi um etidronate and low-dose norethindrone with a long-acting GnRH agoni st (GnRH-a) for prolonged therapy of symptomatic endometriosis. Design : Prospective randomized open label study. Setting: Tertiary care univ ersity-affiliate reproductive medicine program. Patients: Nineteen reg ularly cycling women with laparoscopically diagnosed symptomatic endom etriosis and 18 regularly cycling untreated controls without endometri osis. 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 car bonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9 ) received only supplemental 10 mg norethindrone daily. Group III Volu nteers (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 du al-energy roentgenogram absorptiometry scans); serum estrogens, lipids , and glucose and insulin response to glucose challenge. Results: Pain ful symptoms and extent of endometriosis were reduced in both treatmen t groups. Despite maintenance of a chronically hypoestrogenic state fo r 48 weeks, no changes in bone density over time or in comparison to g roup IH untreated controls were noted. Similarly, no evidence of signi ficant vasomotor symptoms were reported in either treatment group. How ever, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A, levels as well as the ratio o f high-density lipoprotein to LDL were noted only in group II. Conclus ions: The combination of cyclic sodium etidronate and low-dose norethi ndrone with a long-acting GnRH-a served to safely prolong medical ther apy of symptomatic endometriosis. Clinical efficacy achieved.