Review question
Cochrane authors reviewed the evidence on the effectiveness and safety of combined oral contraceptive pills (OCPs) for the treatment of painful menstrual cramps (period pains, also called dysmenorrhoea).
Background
OCPs are readily used as a treatment for menstrual cramps, but the evidence was uncertain about the effects.
Study characteristics
We found 21 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) that compared the effects of OCPs with either placebo (fake pill), other OCPs, or non-steroidal anti-inflammatory medicines that reduce pain and inflammation. The studies included 3723 women. Most women had painful menstrual cramps of at least moderate severity. Manufacturers of OCPs funded 11 studies. We searched the databases in March 2023.
Key results
OCPs compared to placebo
OCPs reduce pain by 0.7 to 1.3 points more on the total dysmenorrhoea scale (range 0 to 6) than placebo in women with menstrual cramps (6 studies with 588 women; high-quality evidence). The six studies that measured improvement as a yes/no category showed that OCPs may reduce pain. Women with a 28% chance of improving on placebo may have a 37% to 60% chance of improving on OCPs (low-quality evidence).
OCPs increase the risk of side effects (59% in placebo group compared to 71% to 86% in OCP group; moderate-quality evidence), and may lead to more serious side effects (1.1% in placebo group compared to 0.5% to 6.8% in OCP group; low-quality evidence).
Irregular bleeding increases among women using OCPs. Women with an 18% risk of irregular bleeding on placebo have a 39% to 60% risk of irregular bleeding on OCPs (high-quality evidence). Moderate-quality evidence found that OCPs probably increase the risk of headaches (17% in placebo group compared to 19% to 35% in OCP group), and nausea (feeling sick; 10% in placebo group compared to 11% to 22% in OCP group).
We are uncertain of the effect of OCP on weight gain.
Low-quality evidence found that OCPs may slightly reduce the need for extra medicine (38% in placebo group compared to 15% to 37% in OCP group), and absence from work (36% in placebo group compared to 11% to 35% in OCP group).
Different OCPs compared to each other
There may be little or no difference between OCPs that contain low or high doses of oestrogen, or between newer and older formulations of OCPs (moderate-quality evidence).
Using continuous OCP (no inactive pills taken as a break between active pills, to postpone bleeding) might reduce pain more than the traditional regimen (low-quality evidence). The traditional regimen is to take active tablets for 21 days and pausing for 7 days (or taking inactive tables for 7 days) where a breakthrough bleeding will usually occur.
There might be little or no difference in the risk of any side effects between the continuous and traditional regimens (65% in traditional group compared to 66% to 80% in continuous group; low-quality evidence).
Due to very low-quality evidence, we are uncertain if there is a difference in the risk of serious side effects (0.9% in traditional group compared to 0.3% to 7.7% in continuous group), headaches (8% in traditional group compared to 4% to 15% in continuous group), nausea (6% in traditional group compared to 3% to 13% in continuous group) or absence from work (9% in traditional group compared to 6% to 18% in continuous group). Continuous use of OCP probably increases irregular bleeding (33% in traditional group compared to 38% to 56% in continuous group; moderate-quality evidence).
These studies did not report on weight gain or the need for extra medicine.
OCP compared to a non-steroidal anti-inflammatory medicine
Due to low-quality evidence, we were unable to determine whether OCPs were more effective than non-steroidal anti-inflammatory medicines. Side effects were not reported.
Quality of the evidence
The quality of the evidence ranged from very low to high. The most important problems were a lack of data and variations in data between studies.
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.
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.