Effects of add-back therapy on bone mineral density and pyridinium crosslinks in patients with endometriosis treated with gonadotropin-releasing hormone agonists

Treatment of endometriosis with gonadotropin-releasing hormone agonists (Gn RHa) is limited to 6 months because of possible adverse effects on bone met abolism. We designed a randomized, double-blind, placebo-controlled, prospe ctive study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 mu g of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant i mprovements in endometriosis, dysmenorrhea, and pelvic pain; effects were s ignificantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher l oss of lumbar spine bone mineral density (BMD). Urinary levels of pyridiniu m crosslinks increased significantly in the GnRHa + placebo group, and decl ined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa.