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/ norethisterone 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 μg nafarelin (n = 12), 200 μg nafarelin (n = 12), or 200 μg nafarelin combined with 1.2 mg norethisterone (n = 25). All were followed for another 6 months without treatment and 47 women completed the whole study 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 determined at baseline and every 3 months. Bone mass was measured at baseline and every 6 months in the forearm and the spine. A significant increase in the parameters of bone resorption was observed after treatment with nafarelin monotherapy, whereas these parameters remained unchanged after combination therapy with norethisterone. A delayed increase in markers of bone formation was observed in all groups, but the response was less pronounced in the combination therapy group. In the 400 μg 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 μg nafarelin groups. Bone mineral density of the spine decreased 2–3% (p < 0.05–0.001) in all groups. In the nafarelin monotherapy groups, a significant increase in serum total cholesterol, LDL-C, and triglycerides was found. Combination therapy with norethisterone decreased this negative effect on the lipid profile. We conclude that combined nafarelin/norethisterone treatment has a less deleterious effect on bone and lipid metabolism than treatment with nafarelin alone.