Gonadotropin-releasing hormone agonist plus "add-back" hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial

OBJECTIVE: To assess the effect of add-back therapy with continuous combined estrogen-progestin on the GnRH agonist-induced hypoestrogenic state and its effectiveness in healing of endometriotic lesions. DESIGN: A prospective, randomized, placebo-controlled, double-blind trial. SETTING: Multiple centers in The Netherlands. PATIENT(S): 41 premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Society scores >/=2). INTERVENTION(S): Patients were randomly assigned to receive a subcutaneous depot formulation of goserelin, 3. 6 mg, every 4 weeks, plus oral placebo or oral continuous combined estradiol-norethisterone acetate add-back therapy daily for 24 weeks. MAIN OUTCOME MEASURE(S): Endometriosis response, bone mineral density, transvaginal ultrasonographic changes, endocrinologic effects, and subjective side effects. RESULT(S): The number of endometriotic implants was significantly reduced in both groups. In the group that received GnRH agonist plus placebo, bone mineral density of the lumbar spine decreased by 5.02%. CONCLUSION(S): The effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy. Bone mineral density of the lumbar spine was maintained and subjective side effects were diminished.