Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis

Arch Gynecol Obstet. 2014 Sep;290(3):513-23. doi: 10.1007/s00404-014-3230-8. Epub 2014 Apr 13.


Objective: A meta-analysis was conducted to determine the effectiveness of using gonadotropin-releasing hormone analogues (GnRH-a), both with and without hormonal add-back therapy, for the management of endometriosis.

Methods: Cochrane library, Ovid (Embase) and Pubmed databases were searched between the years 1998 and 2013 for published, prospective, randomised controlled trials (RCT) that assessed the effectiveness of "add-back" therapy for EMs treatment. The meta-analysis was performed using RevMan V5.0. The main outcome measures were as follows: lumbar spine bone mineral density (BMD) immediately after treatment and after 6 months of follow-up; femoral neck BMD; serum estradiol levels; changes in the Kupperman index score; the pelvic pain score, including dysmenorrhoea and dyspareunia; and pelvic tenderness.

Results: A total of 13 RCT, including 945 participants, were identified. The evidence suggested that "add-back" therapy was more effective for symptom relief than GnRH-a alone. BMD was significantly different when comparing "add-back" therapy to GnRH-a alone, both immediately after treatment and at 6 months. The "add-back" therapy increased serum oestrogen and did not reduce the efficacy of GnRH-a for treating dysmenorrhoea and dyspareunia. A variety of add-back regimens had a same effect for the treatment of endometriosis.

Conclusions: "Add-back" therapy, based on the GnRH-a dose, does not reduce the efficacy of using GNRH-a for the management of endometriosis. "Add-back" therapy reduced the occurrence of side effects that can occur with GnRH-a therapy alone, such as osteoporosis and menopausal syndrome. There were no statistically significant differences when comparing the effectiveness of a variety of "add-back" regimens to each other.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Bone Density / physiology
  • Dose-Response Relationship, Drug
  • Dysmenorrhea / drug therapy
  • Dyspareunia / drug therapy
  • Endometriosis / drug therapy*
  • Estrogens / blood
  • Female
  • Femur Neck / physiology
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Hormone Replacement Therapy*
  • Humans
  • Lumbar Vertebrae / physiology
  • Pain Measurement
  • Randomized Controlled Trials as Topic
  • Uterine Diseases / drug therapy*


  • Estrogens
  • Gonadotropin-Releasing Hormone