Combined oral contraceptive pill for primary dysmenorrhoea

Dysmenorrhoea (painful menstrual cramps) is common and a major cause of pain in women. Combined oral contraceptives (OCPs) are often used in the management of primary dysmenorrhoea, but there is a need for reporting the benefits and harms. Primary dysmenorrhoea is defined as painful menstrual cramps without pelvic pathology.

To evaluate the benefits and harms of combined oral contraceptive pills for the management of primary dysmenorrhoea.

We used standard, extensive Cochrane search methods. The latest search date 28 March 2023.

We included randomised controlled trials (RCTs) comparing all combined OCPs with other combined OCPs, placebo, or management with non-steroidal anti-inflammatory drugs (NSAIDs). Participants had to have primary dysmenorrhoea, diagnosed by ruling out pelvic pathology through pelvic examination or ultrasound.

We used standard methodological procedures recommended by Cochrane. The primary outcomes were pain score after treatment, improvement in pain, and adverse events.

We included 21 RCTs (3723 women). Eleven RCTs compared combined OCP with placebo, eight compared different dosages of combined OCP, one compared two OCP regimens with placebo, and one compared OCP with NSAIDs. OCP versus placebo or no treatment OCPs reduce pain in women with dysmenorrhoea more effectively than placebo. Six studies reported treatment effects on different scales; the result can be interpreted as a moderate reduction in pain (standardised mean difference (SMD) -0.58, 95% confidence interval (CI) -0.74 to -0.41; I² = 28%; 6 RCTs, 588 women; high-quality evidence). Six studies also reported pain improvement as a dichotomous outcome (risk ratio (RR) 1.65, 95% CI 1.29 to 2.10; I² = 69%; 6 RCTs, 717 women; low-quality evidence). The data suggest that in women with a 28% chance of improvement in pain with placebo or no treatment, the improvement in women using combined OCP will be between 37% and 60%. Compared to placebo or no treatment, OCPs probably increase the risk of any adverse events (RR 1.31, 95% CI 1.20 to 1.43; I² = 79%; 7 RCTs, 1025 women; moderate-quality evidence), and may also increase the risk of serious adverse events (RR 1.77, 95% CI 0.49 to 6.43; I² = 22%; 4 RCTs, 512 women; low-quality evidence). Women who received OCPs had an increased risk of irregular bleeding compared to women who received placebo or no treatment (RR 2.63, 95% CI 2.11 to 3.28; I² = 29%; 7 RCTs, 1025 women; high-quality evidence). In women with a risk of irregular bleeding of 18% if using placebo or no treatment, the risk would be between 39% and 60% if using combined OCP. OCPs probably increase the risk of headaches (RR 1.51, 95% CI 1.11 to 2.04; I² = 44%; 5 RCTs, 656 women; moderate-quality evidence), and nausea (RR 1.64, 95% CI 1.17 to 2.30; I² = 39%; 8 RCTs, 948 women; moderate-quality evidence). We are uncertain of the effect of OCP on weight gain (RR 1.83, 95% CI 0.75 to 4.45; 1 RCT, 76 women; low-quality evidence). OCPs may slightly reduce requirements for additional medication (RR 0.63, 95% CI 0.40 to 0.98; I² = 0%; 2 RCTs, 163 women; low-quality evidence), and absence from work (RR 0.63, 95% CI 0.41 to 0.97; I² = 0%; 2 RCTs, 148 women; low-quality evidence). One OCP versus another OCP Continuous use of OCPs (no pause or inactive tablets after the usual 21 days of hormone pills) may reduce pain in women with dysmenorrhoea more effectively than the standard regimen (SMD -0.73, 95% CI -1.13 to 0.34; 2 RCTs, 106 women; low-quality evidence). There was insufficient evidence to determine if there was a difference in pain improvement between ethinylestradiol 20 μg and ethinylestradiol 30 μg OCPs (RR 1.06, 95% CI 0.65 to 1.74; 1 RCT, 326 women; moderate-quality evidence). There is probably little or no difference between third- and fourth-generation and first- and second-generation OCPs (RR 0.99, 95% CI 0.93 to 1.05; 1 RCT, 178 women; moderate-quality evidence). The standard regimen of OCPs may slightly increase the risk of any adverse events over the continuous regimen (RR 1.11, 95% CI 1.01 to 1.22; I² = 76%; 3 RCTs, 602 women; low-quality evidence), and probably increases the risk of irregular bleeding (RR 1.38, 95% CI 1.14 to 1.69; 2 RCTs, 379 women; moderate-quality evidence). Due to lack of studies, it is uncertain if there is a difference between continuous and standard regimen OCPs in serious adverse events (RR 0.34, 95% CI 0.01 to 8.24; 1 RCT, 212 women), headaches (RR 0.94, 95% CI 0.50 to 1.76; I² = 0%; 2 RCTs, 435 women), or nausea (RR 1.08, 95% CI 0.51 to 2.30; I² = 23%; 2 RCTs, 435 women) (all very low-quality evidence). We are uncertain if one type of OCP reduces absence from work more than the other (RR 1.12, 95% CI 0.64 to 1.99; 1 RCT, 445 women; very low-quality evidence). OCPs versus NSAIDs There were insufficient data to determine whether OCPs were more effective than NSAIDs for pain (mean difference -0.30, 95% CI -5.43 to 4.83; 1 RCT, 91 women; low-quality evidence). The study did not report on adverse events.

OCPs are effective for treating dysmenorrhoea, but they cause irregular bleeding, and probably headache and nausea. Long-term effects were not covered in this review. Continuous use of OCPs was probably more effective than the standard regimen but safety should be ensured with long-term data. Due to lack of data, we are uncertain whether NSAIDs are better than OCPs for treating dysmenorrhoea.