Oral contraceptives for pain associated with endometriosis

Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The combined oral contraceptive pill (COCP) is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited.

To determine the effectiveness, safety and cost-effectiveness of oral contraceptive preparations in the treatment of painful symptoms ascribed to the diagnosis of laparoscopically proven endometriosis.

We searched the following from inception to 19 October 2017: the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane CENTRAL Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial registers ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform (WHO ICTRP). We also handsearched reference lists of relevant trials and systematic reviews retrieved by the search.

We included randomised controlled trials (RCT) of the use of COCPs in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis that had been made visually at a surgical procedure.

Two review authors independently assessed study quality and extracted data. One review author was an expert in the content matter. We contacted study authors for additional information. The primary outcome was self-reported pain (dysmenorrhoea) at the end of treatment.

Five trials (612 women) met the inclusion criteria. Only three trials (404 women) provided data that were suitable for analysis.Combined oral contraceptive pill versus placeboTwo trials compared COCP with a placebo. These studies were at high risk of bias. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence very low. Evidence was downgraded for imprecision as it was based on a single, small trial and for the visual analogue scale data there were wide confidence intervals (CIs). There appeared to have been substantial involvement of the pharmaceutical company funding the trials.Treatment with the COCP was associated with an improvement in self-reported pain at the end of treatment as evidenced by a lower score on the Dysmenorrhoea verbal rating scale (scale 0 to 3) compared with placebo (mean difference (MD) -1.30 points, 95% CI -1.84 to -0.76; 1 RCT, 96 women; very low quality evidence), a lower score on the Dysmenorrhoea visual analogue scale (no details of scale) compared with placebo (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women; very low quality evidence) and a reduction in menstrual pain from baseline to the end of treatment (MD 2.10 points, 95% CI 1.38 to 2.82; 1 RCT, 169 women; very low quality evidence).Combined oral contraceptive pill versus medical therapiesOne underpowered trial compared the COCP with another medical treatment (goserelin). The study was at high risk of bias; the trial was unblinded and there was insufficient detail to judge allocation concealment and randomisation. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence ranged from low to very low.At the end of treatment, the women in the goserelin group were amenorrhoeic and therefore no comparisons could be made between the groups for the primary outcome. At six months' follow-up, there was no clear evidence of a difference between women treated with the COCP and women treated with goserelin for measures of dysmenorrhoea on a visual analogue scale (scale 1 to 10) (MD -0.10, 95% CI -1.28 to 1.08; 1 RCT, 50 women; very low quality evidence) or a verbal rating scale (scale 0 to 3) (MD -0.10, 95% CI -0.99 to 0.79; 1 RCT, 50 women; very low quality evidence). At six months' follow-up, there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain as measured by the visual analogue scale (risk ratio (RR) 0.36, 95% CI 0.02 to 8.43; 1 RCT, 50 women; very low quality evidence) or the verbal rating scale (RR 1.00, 95% CI 0.93 to 1.08; 1 RCT, 49 women; low quality evidence).

Based on the limited evidence from two trials at high risk of bias and limited data for the prespecified outcomes for this review, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with placebo and the findings cannot be generalised.Based on the limited evidence from one small trial that was at high risk of bias, there is insufficient evidence to make a judgement on the effectiveness of the COCP compared with other medical treatments. Only one comparison was possible, with the medical intervention being goserelin, and the findings cannot be generalised.Further research is needed to fully evaluate the role of COCPs in managing pain-related symptoms associated with endometriosis. There are other formulations of the combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives which this review did not cover but should be considered in future updates.