Gonadotrophin-releasing hormone analogues for pain associated with endometriosis: Commentary

Abstract

BACKGROUND: Endometriosis is a common gynecological condition, characterized 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 premenopausal women. GnRHas can be administered intranasally, by subcutaneous injection, or intramuscular injection. They are thought to result in down regulation of the pituitary and induce a hypogonadotrophic hypogonadal state. OBJECTIVE: To determine the effectiveness and safety of GnRHas in the treatment of the painful symptoms associated with endometriosis. SEARCH STRATEGY: 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 randomized controlled trials. SELECTION CRITERIA: Randomized controlled trials of GnRHas as treatment for pain associated with endometriosis compared with 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 (RR) was used as the measure of effect for dichotomous data. For continuous data, mean differences or standardized mean differences were used. MAIN RESULTS: Forty one trials (n=4935 women) were included. The evidence suggested that GnRHas were more effective at symptom relief than placebo or no treatment. There was no statistically significant difference between GnRHas and danazol for dysmenorrhoea RR 0.98 (95% confidence interval [CI], 0.92 to 1.04, P = .53). This equates to 3 fewer women per 1000 (95% CI, 12 to 6) with symptomatic pain relief in the GnRHa group. More adverse events were reported in the GnRHa group. There was a benefit in overall resolution for GnRHas RR1.10 (95% CI, 1.01 to 1.21, P = .03) compared with danazol. There was no statistically significant difference in overall pain between GnRHas and levonorgestrel SMD -0.25 (95% CI, -0.60 to 0.10, P = .46). Evidence was limited on optimal dosage or duration of treatment for GnRHas. No route of administration appeared superior to another. AUTHORS' CONCLUSION: GnRHas appear to be more effective at relieving pain associated with endometriosis than placebo or no treatment. There was no evidence of a difference in pain relief between GnRHas and danazol, although more adverse events were reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel, and no studies compared GnRHas with analgesics. © 2011 The American College of Obstetricians and Gynecologists.