Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Abstract

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 µg 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 improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined 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.

Treatment of Endometriosis with the GnRHa Deslorelin and Add-Back Estradiol and Supplementary Testosterone

“…It is generally not considered appropriate to treat with a GnRHa alone because of a substantial reduction in bone mineral density (BMD), significant symptoms of estrogen deficiency such as hot flashes [ 11 , 12 ], and sexual complaints such as the loss of libido and vaginal dryness. The use of add-back sex steroids with GnRH analogues is aimed at preventing the negative effects of the GnRHa while maintaining an effective therapy for endometriosis [ 13 – 19 ].…”

The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study

“…Contradicting this result Moghissi et al (5) and others have shown a positive effect on BMD by hormone replacement therapy (HRT). However, add‐back therapy with estrogen reduces the positive effect of GnRH analog therapy on endometriosis (6). Parathyroid hormone prevents bone loss in women with endometriosis treated with GnRH analogs (7), whereas nasal administration of calcitonin is ineffective (8).…”