Evidence of similar increases in bone turnover during nafarelin and danazol use in women with endometriosis

Abstract

Medical 'oophorectomy' by GnRH agonist or danazol is an effective treatment for endometriosis. Since increased bone loss is a potential risk of hypoestrogenism, we compared the effect of nafarelin and danazol treatment on bone metabolism. Twelve patients with laparoscopically confirmed endometriosis received nafarelin (400 micrograms day intranasally) and six patients danazol (600 mg day orally) for 6 months. Both treatments had already led to hypoestrogenism (E2 less than 21.6 pg/ml) after 3 months. They both were accompanied by an approximately 50% rise in 24-h urinary hydroxyproline output, suggesting accelerated bone resorption at 6 months; yet urinary calcium output did not change significantly. Serum osteocalcin rose by 80-120% and bone alkaline phosphatase activity by 34-40%, suggesting stimulated bone formation at the same time. No detectable changes ensued in cortical bone mineral content in the distal radius or in serum levels of calcium, calcitonin, parathyroid hormone, or aminoterminal propeptide of type III collagen. Three months after treatment, hydroxyproline output, serum osteocalcin and bone alkaline phosphatase were still elevated in women taking nafarelin, whereas only serum osteocalcin was elevated in women taking danazol. Our data thus suggest that bone turnover was increased during nafarelin and danazol therapy and that this effect was reversible.