The effectiveness of oral contraceptives for endometriosis pain

Endometriosis can result in reduced quality of life and significant burden to the health system.

This evidence summary presents the best available evidence regarding the effectiveness of oral contraceptives for the management of pain associated with endometriosis. For the full review, refer to Oral contraceptives for pain associated with endometriosis.¹

Background
The prevalence of endometriotic disease is about 5% of the population. Women between the ages of 25 and 35 are most affected. Risk factors of developing endometriosis include: family history, starting menstruation before the age of 12, experiencing periods lasting more than seven days, immune system disorders and abdominal surgery that can disrupt the endometrium.

Almost two thirds of women in the US received an endometriosis-related surgical procedure within one year of the initial diagnosis, which contributed to the significant healthcare costs associated with the condition.^2,3

The management of endometriosis relies on reducing symptoms and the use of hormonal therapies which result in atrophy of the ectopic endometrium. Surgery is also an option and most often is associated with pain relief, but its benefit is often limited.

Low dose combined oral contraceptive pill (COCP) was observed to reduce menstrual flow and decreased cell proliferation and increased apoptosis.⁴ COCPs have an advantage over other hormonal treatments in that they can be taken for long periods of time during reproductive life and are generally more acceptable to women than other treatment.⁵

The results of a recent review addressing the efficacy of low dose oral contraceptives for the management of pain for patients with endometriosis are summarised below.

Results

• The following databases were searched from inception until 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). Hand searching of all the reference lists of relevant trials and systematic reviews retrieved was also undertaken.
• The search yielded five trials including a total of 612 women who met the inclusion criteria. Only three trials with 404 women provided data that were suitable for inclusion in the results.
• The main primary outcome is self-reported pain (dysmenorrhoea) at the end of treatment.
• The secondary outcome measures included cyclical pain (non-menstrual), pelvic pain, patient satisfaction, withdrawal from treatment, cost of treatment and adverse events.
• Two trials compared COCP with a placebo. Treatment with 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). There was also a lower score on the Dysmenorrhoea visual analogue scale compared with placebo (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women) 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). All these results were based on very low-quality evidence.
• One study compared COCP with goserelin. The women in the goserelin group were amenorrhoeic and therefore there were no results reported for the primary outcome. At six months’ follow-up, there was no difference between women treated with 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) or a verbal rating scale (scale 0 to 3) (MD -0.10, 95% CI -0.99 to 0.79; 1 RCT, 50 women) based on very low-quality evidence.

Characteristics of studies
Only randomised controlled trials (RCT) using COCP versus placebo or other treatments in the management of symptomatic endometriosis were included. No other study designs were included.

Quality of the research
Studies included in the report had high or unclear risk of bias. Overall, the quality of the evidence was low. The main sources of bias were selection, detection, attrition and selective reporting of data.

Conclusion
There is insufficient evidence to make a judgement on the effectiveness of COCP compared with other medical treatments for the treatment of pain associated with endometriosis, due to the small number of studies and the high risk of bias associated with them.

Implication for practice and research
Further research should address larger studies to evaluate the role of COCP in managing pain-related symptoms associated with endometriosis.

Other formulations of combined hormonal contraception such as the transdermal patch, vaginal ring or combined injectable contraceptives should also be considered.

References

1. Brown J, Crawford TJ, Datta S, et al. Oral contraceptives for pain associated with endometriosis. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD001019. DOI: 10.1002/14651858. CD001019.pub3.
2. Vercellini P, Viganò P, Somigliana E, et al. Endometriosis: pathogenesis and treatment. Nature Reviews Endocrinology 2014;10(5):261.
3. Mirkin D, Murphy-Barron C, Iwasaki, K. Actuarial analysis of private payer administration claims data for women with endometriosis. J Manag Care Pharm 2007;13:262–272.
4. Meresman GF, Auge L, Baranoa RI, et al. Oral contraceptives suppress cell proliferation and enhance apoptosis of ectopic endometrial tissue from patients with endometriosis. Fertility and Sterility 2002;77(6):1141–7.
5. Brynhildsen J. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks. Therapeutic Advances in Drug Safety 2014;5(5):201–13.