Gonadotrophin-releasing hormone analogues for pain associated with endometriosis

Abstract

Background: Endometriosis is a common gynaecological condition, characterised by the presence of endometrial tissue in sites other than the uterine cavity (excluding adenomyosis) that frequently presents with pain. The gonadotrophin-releasing hormone analogues (GnRHas) comprise one intervention that has been offered for pain relief in pre-menopausal women. GnRHas can be administered intranasally, by subcutaneous, or intramuscular injection. They are thought to result in down regulation of the pituitary and induce a hypogonadotrophic hypogonadal state. Objectives: To determine the effectiveness and safety of GnRHas in the treatment of the painful symptoms associated with endometriosis. Search methods: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialist register, CENTRAL, MEDLINE, EMBASE, PSYCInfo and CINAHL were conducted in April 2010 to identify relevant randomised controlled trials (RCTs). Selection criteria: RCTs of GnRHas as treatment for pain associated with endometriosis versus no treatment, placebo, danazol, intra-uterine progestagens, or other GnRHas were included. Trials using add-back therapy, oral contraceptives, surgical intervention, GnRH antagonists or complementary therapies were excluded. Data collection and analysis: Quality assessment and data extraction were performed independently by two reviewers. The primary outcome was pain relief. Relative risk was used as the measure of effect for dichotomous data. For continuous data, mean differences or standardised mean differences were used. Main results: Forty one trials (n=4935 women) were included. The evidence was inconsistent as to whether GnRHas were more effective at symptom relief than no treatment/placebo (low quality evidence) (see SoFs 1 and 2). The evidence was also inconsistent as to whether GnRHas were more effective than Danazol (low or very low quality evidence) (see SoF 3) More adverse events were reported in the GnRHa group,There was no statistically significant difference in overall pain relief between GnRHas and levonorgestrel intrauterine system (LNG IUS) SMD -0.25 (95%CI -0.60 to 0.10, P=0.46, moderate quality evidence). Evidence was limited on optimal dosage,duration and route of administration for treatment for GnRHas. Authors' conclusions: It is unclear whether GnRHas is more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no consistent evidence of a difference in pain relief between GnRHas and danazol although more adverse events were reported in the GnRHa groups. There was also no evidence of a difference in pain relief between GnRHas and LNG IUS. No studies compared GnRHas with analgesics.