DEPOT LEUPROLIDE ACETATE VERSUS DANAZOL IN THE TREATMENT OF WOMEN WITH SYMPTOMATIC ENDOMETRIOSIS - A MULTICENTER, DOUBLE-BLIND RANDOMIZED CLINICAL-TRIAL - ASSESSMENT OF SAFETY

OBJECTIVES: This is the first multicenter, double-blind randomized cli nical trial that compares a depot gonadotropin-releasing hormone agoni st with danazol in the treatment of endometriosis. Efficacy results ha ve been previously reported; this report focuses on safety data. STUDY DESIGN: A total of 270 patients from 22 centers were randomly selecte d to receive either leuprolide acetate depot (3.75 mg injected monthly ) or danazol (800 mg administered orally daily). Safety outcomes inclu ded adverse effects, clinical laboratory changes, and bone mineral den sity changes. RESULTS: Most patients receiving either drug reported si de effects, most of which were related to the hypoestrogenism of leupr olide (e.g., vasodilatation) and relative hyperandrogenism of danazol (e.g., weight gain). Similarly small numbers of patients dropped out o f the two treatment groups because of the side effects encountered. Le uprolide depot caused a greater decrease in bone density; preliminary data suggest a return to baseline on cessation of the drug. Danazol wa s associated with alteration of serum lipids, specifically a significa nt decrease in high-density lipoprotein. CONCLUSIONS: Although side ef fects were commonly reported in both groups, the drugs were similarly safe in terms of the absence of serious complications and the results of cessation of therapy. Side effects were largely reversible on disco ntinuation of medication. More longitudinal data are necessary before the possibility of long-term risks can be excluded, especially as they pertain to bone mineral density and lipids.