TREATMENT OF ENDOMETRIOSIS WITH THE LUTEINIZING-HORMONE-RELEASING HORMONE AGONIST NAFARELIN - EFFECT ON BONE TURNOVER AND BONE MASS

We investigated the effect of nafarelin monotherapy and nafarelin/nore thisterone combination therapy on bone turnover and bone mass. A total of 49 premenopausal women with endometriosis confirmed by laparoscopy were randomized to double-blind treatment for 6 months with 400 mu g nafarelin (n = 12), 200 mu g nafarelin (n = 12), or 200 mu g nafarelin combined with 1.2 mg norethisterone (n = 25). All were followed for a nother 6 months without treatment and 47 women completed the whole stu dy period. Parameters for bone formation (plasma bone Gla protein and serum total alkaline phosphatase) and bone resorption (fasting urinary hydroxyproline and calcium corrected for creatinine excretion) were d etermined at baseline and every 3 months. Bone mass was measured at ba seline and every 6 months in the forearm and the spine. A significant increase in the parameters of bone resorption was observed after treat ment with nafarelin monotherapy, whereas these parameters remained unc hanged after combination therapy with norethisterone. A delayed increa se in markers of bone formation was observed in all groups, but the re sponse was less pronounced in the combination therapy group. In the 40 0 mu g nafarelin group we observed a delayed 1% (p < 0.05) decrease in the bone mineral content of the forearm; no changes were observed in this region in the 200 mu g nafarelin groups. Bone mineral density of the spine decreased 2-3% (p < 0.05-0.001) in all groups. In the nafare lin monotherapy groups, a significant increase in serum total choleste rol, LDL-C, and triglycerides was found. Combination therapy with nore thisterone decreased this negative effect on the lipid profile. We con clude that combined nafarelin/norethisterone treatment has a Less dele terious effect on bone and lipid metabolism than treatment with nafare lin alone.