Background

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.

Objectives

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

Search methods

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

Selection criteria

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.

Data collection and analysis

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

Main results

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.

Authors' conclusions

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.

Keywords: Female; Humans; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents, Non-Steroidal/adverse effects; Contraceptives, Oral, Combined; Contraceptives, Oral, Combined/adverse effects; Dysmenorrhea; Dysmenorrhea/drug therapy; Headache; Muscle Cramp

Summary of findings 1. Combined OCP compared to placebo or no treatment for primary dysmenorrhoea.

Summary of findings 2. Combined low‐dose OCP compared to another combined low‐dose OCP for primary dysmenorrhoea.

Summary of findings 3. NSAID compared to combined OCP for primary dysmenorrhoea.

Description of the condition

Dysmenorrhoea is painful menstrual cramps. It is a common gynaecological problem that affect as many as 50% to 60% of women; around 15% of these women experience enough pain to temporarily render them incapacitated, which results in absences from work or school (Burnett 2005;Dawood 2006;Ju 2014). The impacts are significant, both in terms of quality of life and loss of earnings.

Dysmenorrhoea is commonly subcategorised into primary and secondary dysmenorrhoea. Menstrual pain without organic pathology is considered to be primary dysmenorrhoea (Coco 1999). When the pelvic pain is associated with an identifiable pathological condition, such as endometriosis or ovarian cysts, it is considered to be secondary dysmenorrhoea.

The initial onset of primary dysmenorrhoea is usually at, or shortly after, menarche (within 6 to 12 months), when ovulatory cycles are established. The pain duration commonly ranges from 8 to 72 hours, and is associated with menstrual flow. In contrast, secondary dysmenorrhoea is more likely to develop years after the onset of menarche, and occur premenstrually, as well as during menstruation.

Description of the intervention

As early as 1937, research has shown that dysmenorrhoea responds favourably to ovulation inhibition, and that the synthetic hormones in the combined oral contraceptive pill (OCP) can be used to manage dysmenorrhoea (Karnaky 1975). These hormones act by suppressing ovulation and lessening the endometrial lining of the uterus. Therefore, menstrual fluid volume decreases, along with the level of prostaglandins produced, which then reduces dysmenorrhoea by decreasing uterine motility and uterine cramping.

The use of combined OCPs has been advocated as a treatment for primary dysmenorrhoea since their introduction for general use in 1960. OCP use for secondary dysmenorrhoea has also been questioned; although this type of treatment may have some favourable effect on dysmenorrhoea, ultimately, the organic cause of the pain must be addressed (ACOG 2018).

Progestogens are traditionally categorised into first, second, third, and fourth generation, based on when they were synthesised (Regidor 2018). The categories might share some biochemical, as well as clinical features, even though the traditional categories are being challenged.

How the intervention might work

OCPs reduce the amount of endometrial tissue by inhibiting the buildup during the normal menstrual cycle. Prostaglandins and leukotrienes produced in the endometrium are responsible for uterine contractions, and are abundant in women reporting dysmenorrhoea (Harel 2008). Women using OCPs produce less prostaglandin due to the decreased amount of tissue, which leads to less intrauterine pressure and less pain (Harel 2008). Inhibition of ovulation may also limit the amount of prostaglandins produced.

Why it is important to do this review

Although combined OCPs have long been promoted as the management for primary dysmenorrhoea, very few trials have been conducted to study the efficacy and associated adverse events of their use. In addition, most of these trials are of poor methodological quality, which exposes them to a variety of biases. This is important to recognise in this review.

Dysmenorrhoea is a debilitating gynaecological condition that impacts significantly on women around the world. Not only does it cause a decrease in personal health, but having to take time off work or school also results in loss of productivity, eventually leading to economic loss. Therefore, proper management of dysmenorrhoea will benefit individuals and society.

There has also been debate around the adverse events of OCPs, and whether they were worth the benefits in managing dysmenorrhoea. Therefore, this review aimed to establish the usefulness of OCPs in managing dysmenorrhoea in the general female population, by comparing all relevant randomised controlled trials (RCTs).

Criteria for considering studies for this review

Search methods for identification of studies

We sought all reports that described (or might have described) RCTs of combined OCPs in the treatment of primary dysmenorrhoea. The search strategies were developed in consultation with the Information Specialist from the Cochrane Gynaecology and Fertility Group. We did not restrict the search by language or date.

Data collection and analysis

Description of studies

Risk of bias in included studies

SeeFigure 2 andFigure 3.

Effects of interventions

See:Table 1;Table 2;Table 3

Summary of main results

We included 21 RCTs in this updated review; 11 compared different OCP preparations with placebo only, eight compared different preparations with each other, one compared different OCPs with each other and placebo (three‐armed study), and one compared OCPs with NSAIDs.

OCPs are more effective than placebo at treating dysmenorrhoea. However, they have adverse effects in the form of irregular bleeding, headache, and nausea. We did not cover long‐term adverse effects (over six months) in this review due to lack of long‐term RCTs. SeeTable 1.

Continuous use of OCPs without pause compared to the standard 21‐day treatment/seven‐day pause regimen may be superior at treating dysmenorrhoea, but little is known about adverse effects in both the short‐ and long‐term. One study including 38 women indicated weight gain in the continuous group. SeeTable 2.

We found no differences between the different OCPs.

There was insufficient evidence to estimate the effects of NSAIDs compared to OCPs.

Overall completeness and applicability of evidence

OCPs are widely advocated as standard treatment for women with primary dysmenorrhoea, which, until recently, was based on scant evidence. This review confirmed that OCPs are beneficial for pain due to primary dysmenorrhoea, which has also been found in observational studies (Milsom 1984;Milsom 1990).

Inclusion criteria and treatment regimens seemed relevant. Better outcome reporting and longer follow‐up could give more relevant information.

Continuous usage of OCPs is also being advocated. Even though this review confirmed that OCPs are effective, it also highlighted the lack of data on safety. This is due to poor reporting, but also limited follow‐up.

Another issue that needs to be considered is that the use of OCPs as treatment for dysmenorrhoea does not just depend on their efficacy, but also the suitability of OCPs for the woman. If a woman wants to become pregnant or has contraindications to the OCP, then the OCP would be an unsuitable treatment option at that time.

There are also difficulties in extrapolating the results of this review to modern‐day populations, as some of the older included trials used higher levels of oestrogen than typically used today. However, the results from these older studies do not seem to differ from the newer studies.

Quality of the evidence

Due to poor reporting, many bias domains were unclear. Five studies were not blinded, which can cause bias especially when the outcome was subjective.

However, the studies that provided data for pain score comparing OCP with placebo or no treatment were at low or unclear risk of blinding (selection bias). Most studies were sponsored by drug manufacturers but aside from this there was no risk of bias, and no imprecision, substantial heterogeneity, or indirectness and therefore pain score was not downgraded and remained as high quality. Two trials could not be included because they only reported mean change, but the results were similar, and supported the conclusion of the meta‐analysis.

Pain improvement as a dichotomous outcome was downgraded two levels for inconsistency and indirectness, and the quality of evidence was therefore assessed as low.

For the comparison of continuous contraceptives with standard regimen, the studies were unblinded and, therefore, we downgraded the evidence as participants could easily guess allocation since one group would get withdrawal bleeding after 21 days. We also downgraded for imprecision, which resulted in low‐quality evidence.

The manufacturer of the contraceptive being investigated funded 11/21 studies; this type of funding has been linked to increased effect estimates (Lundh 2017). Another seven trials had unclear funding; only three had independent funding.

Potential biases in the review process

There were methodological problems associated with quantifying and grading the pain of dysmenorrhoea. Assessment instruments used in quantifying dysmenorrhoea are based on a woman's self‐report and as such, are subject to obvious bias. In addition, all the trials categorised pain using different scales, which may be a significant source of heterogeneity in this review. We attempted to identify and include all relevant studies through database and handsearching. Our protocol did not specify withdrawal from study and withdrawal due to adverse events, but we consider they offer a better understanding of adverse events, which were initially specified.

Agreements and disagreements with other studies or reviews

Very few systematic reviews have been published on contraceptives for primary dysmenorrhoea since the last publication of this review. OCPs are widely used, even though the previous version of this review did not find an effect (Wong 2009). Since the previous version, more studies have been published that support the use of contraceptives. In this review, we also included the continuous use of combined OCP, which seems to be even more efficient than the traditional regimen. This makes biological sense, as bleeding will cause uterine contractions, which can cause pain.

Implications for practice.

Implications for research.

Appendix 1. Cochrane Gynaecology and Fertility Group (CGF) specialised register search strategy

Searched 28 March 2023

ProCite platform

Keywords CONTAINS "combined" or "Combination" or "OCP" or "oral contraceptive" or "oral contraceptives" or "progestagen" or "Progesterone" or "progestin" or "progestogen" or "progestogens" or "Norgestrel" or "noresthisterone" or "desogestral" or "desogestrel" or "gestodene" or "gestoden" or "oestrogen" or "oestrodiol" or "estradiol" or "estrogen" or Title CONTAINS "combined" or "Combination" or "OCP" or "oral contraceptive" or "oral contraceptives" or "progestagen" or "Progesterone" or "progestin" or "progestogen" or "progestogens" or "Norgestrel" or "noresthisterone" or "desogestral" or "desogestrel" or "gestodene" or "gestoden" or "oestrogen" or "oestrodiol" or "estradiol" or "estrogen"

AND

Keywords CONTAINS "dysmenorrhea" or "Dysmenorrhea‐Symptoms" or "dysmenorrhoea" or "pelvic pain" or "menstrual cramps" or "menstrual distress" or "menstrual pain" or "pain‐dysmenorrhea" or "pain‐pelvic" or Title CONTAINS "dysmenorrhea" or "Dysmenorrhea‐Symptoms" or "dysmenorrhoea" or "pelvic pain" or "menstrual cramps" or "menstrual distress" or "menstrual pain" or "pain‐dysmenorrhea" or "pain‐pelvic"

(276 records in total)

Appendix 2. CENTRAL via the Cochrane Register of Studies Online (CRSO) search strategy

Searched 28 March 2023

Web platform

#1 MESH DESCRIPTOR Dysmenorrhea EXPLODE ALL TREES 740
#2 dysmenorrh*:TI,AB,KY 2700
#3 (pain* adj5 menstrua*):TI,AB,KY 569
#4 (menstrua* adj3 pain* ):TI,AB,KY 831
#5 (pain* adj5 period*):TI,AB,KY 5783
#6 (cyclic adj3 pain* ):TI,AB,KY 58
#7 #1 OR #2 OR #3 OR #4 OR #5 OR #6 8869
#8 MESH DESCRIPTOR Contraceptives, Oral EXPLODE ALL TREES 5128
#9 (oral contracept*):TI,AB,KY 3784
#10 OCP:TI,AB,KY 312
#11 MESH DESCRIPTOR Progestins EXPLODE ALL TREES 3293
#12 (progesta* or progestogen* or gestagen*):TI,AB,KY 1555
#13 MESH DESCRIPTOR Ethinyl Estradiol EXPLODE ALL TREES 1633
#14 MESH DESCRIPTOR Levonorgestrel EXPLODE ALL TREES 1059
#15 MESH DESCRIPTOR Desogestrel EXPLODE ALL TREES 494
#16 MESH DESCRIPTOR Norethindrone EXPLODE ALL TREES 858
#17 (gestodene or desogestrel or norethisterone):TI,AB,KY 1717
#18 (NORGESTIMATE or norgestrel or levonorgestrel):TI,AB,KY 2784
#19 MESH DESCRIPTOR Estrogens EXPLODE ALL TREES 8561
#20 (estrogen* or oestrogen*):TI,AB,KY 15191
#21 MESH DESCRIPTOR Estradiol EXPLODE ALL TREES 4949
#22 Estradiol:TI,AB,KY 11657
#23 #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 28796
#24 #7 AND #23 622

Appendix 3. MEDLINE search strategy

Searched from 1946 to 28 March 2023

Ovid platform

1 Menstruation Disturbances/ (7464)
2 pelvic pain/ or dysmenorrhea/ (10586)
3 menstrual disorder$.ti,ab,sh. (2003)
4 (pelvi$ adj3 pain).tw. (12296)
5 dysmenorrh$.ti,ab,sh. (8182)
6 (pain$ adj5 menstrua$).tw. (2319)
7 (pain$ adj5 period$).tw. (7903)
8 or/1‐7 (37456)
9 contraceptives, oral/ or contraceptives, oral, combined/ (23531)
10 oral contracept$.tw. (27291)
11 OCP.tw. (3159)
12 exp Progestins/ (71737)
13 (progesta$ or progestogen$ or gestagen$).tw. (11455)
14 ethinyl estradiol/ or ethinyl estradiol‐norgestrel combination/ (9081)
15 norgestrel/ or levonorgestrel/ (6371)
16 desogestrel/ or norethindrone/ (5816)
17 (gestodene or desogestrel or norethisterone).tw. (3538)
18 (NORGESTIMATE or norgestrel or levonorgestrel).tw. (6396)
19 exp Estrogens/ (169060)
20 (estrogen$ or oestrogen$).tw. (173432)
21 Estradiol/ or estrodiol.tw. (85794)
22 or/9‐21 (330246)
23 8 and 22 (4791)
24 randomized controlled trial.pt. (589336)
25 controlled clinical trial.pt. (95226)
26 randomized.ab. (597161)
27 randomised.ab. (118053)
28 placebo.tw. (243227)
29 clinical trials as topic.sh. (200907)
30 randomly.ab. (404664)
31 trial.ti. (281766)
32 (crossover or cross‐over or cross over).tw. (97236)
33 or/24‐32 (1591677)
34 exp animals/ not humans.sh. (5105607)
35 33 not 34 (1465568)
36 23 and 35 (762)

Appendix 4. Embase search strategy

Searched from 1980 to 28 March 2023

Ovid platform

1 exp dysmenorrhea/ or exp menorrhagia/ (24141)
2 dysmenorrh$.tw. (9693)
3 (menstrual adj5 cramp$).tw. (358)
4 (menstrual adj5 pain).mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword heading word, floating subheading word, candidate term word] (2740)
5 (pelvic adj5 pain).ti,ab,sh. (21549)
6 (pain$ adj5 menstruat$).tw. (944)
7 (period$ adj5 pain$).tw. (12013)
8 exp contraceptives, oral/ or exp contraceptives, oral, combined/ or exp contraceptives, oral, hormonal/ or exp contraceptives, oral, sequential/ or exp contraceptives, oral, synthetic/ (61553)
9 ocp.tw. (4301)
10 exp estrogens/ or exp estrogens, non‐steroidal/ or exp progestins/ (357332)
11 $estrogen.tw. (162469)
12 exp Progesterone/ (88860)
13 desogestrel/ or exp norgestrel/ or exp ethinyl estradiol‐norgestrel combination/ or levonorgestrel/ (17701)
14 progestagen.tw. (1334)
15 norethisterone.tw. (2056)
16 gestodene.tw. (865)
17 norgestimate.tw. (435)
18 ethinyl estradiol.tw. (3637)
19 oestradiol.tw. (12930)
20 oral contraceptive$.tw. (27336)
21 (estrogen$ or estradiol).tw. (239314)
22 levonorgestrel.tw. (7007)
23 or/1‐7 (56844)
24 or/8‐22 (477290)
25 23 and 24 (8392)
26 Clinical Trial/ (1060609)
27 Randomized Controlled Trial/ (771234)
28 exp randomization/ (98628)
29 Single Blind Procedure/ (51066)
30 Double Blind Procedure/ (205438)
31 Crossover Procedure/ (74464)
32 Placebo/ (386427)
33 Randomi?ed controlled trial$.tw. (320444)
34 Rct.tw. (52568)
35 random allocation.tw. (2508)
36 randomly allocated.tw. (44558)
37 allocated randomly.tw. (2893)
38 (allocated adj2 random).tw. (860)
39 Single blind$.tw. (31042)
40 Double blind$.tw. (236069)
41 ((treble or triple) adj blind$).tw. (1814)
42 placebo$.tw. (358679)
43 prospective study/ (860703)
44 or/26‐43 (2713586)
45 case study/ (97041)
46 case report.tw. (514904)
47 abstract report/ or letter/ (1261085)
48 or/45‐47 (1857784)
49 44 not 48 (2648637)
50 25 and 49 (2195)

Appendix 5. PsycINFO search strategy

Searched from 1806 to 28 March 2023

Ovid platform

1 exp Dysmenorrhea/ (263)
2 (pelvi$ adj3 pain).tw. (812)
3 dysmenorrh$.tw. (484)
4 (pain$ adj5 menstrua$).tw. (322)
5 (pain$ adj5 period$).tw. (1140)
6 or/1‐5 (2557)
7 exp Oral Contraceptives/ (1045)
8 oral contracept$.tw. (1720)
9 OCP.tw. (147)
10 or/7‐9 (2087)
11 6 and 10 (45)

Appendix 6. Data extraction form

Trial characteristics

1 Citation
2 E‐mail to corresponding author
3 Name of corresponding author
4 Design (parallel, cross‐over, factorial)
5 Blinding
6 Study location
7 Study duration
9 Study Started – Ended
10 Inclusion criteria
11 Exclusion criteria
12 Sponsor
13 Premature stoppage
14 Primary outcome (from protocol if available)
15 Secondary outcomes
16 ClinicalTrials.gov registration?

Interventions 
17 Estrogen (type and exact dose)
18 Progesteron (type and dose)
19 Progesteron generation
20 Treatment regimen (i.e. 21 days of active treatment and 7 days of pause)

Baseline (for each treatment arm)
21 Average age
22 Average age – standard deviation
23 Average BMI
24 Average BMI – standard deviation
25 Average menstrual pain
26 Average menstrual pain – standard deviation
27 Name and description of menstrual scale (i.e. VAS 0 to 100 mm)
28 Alternative scale – average menstrual pain
29 Alternative scale – average menstrual pain – standard deviation
30 N (randomised)
31 Investigations done at baseline

Post treatment (for each treatment arm)
32 Number of participants measured primary outcome
33 Number of participants with improvement (participants‐reported or dichotomised scale based on predefined values)
34 Definition of improvement
35 Average menstrual pain
36 Average menstrual pain – standard deviation
37 Mean change from baseline (if reported instead of post treatment value)
38 Alternative scale – average menstrual pain
39 Alternative scale – average menstrual pain – standard deviation

Post treatment (for each treatment arm) – secondary outcomes
40 Ratio of participants missing school/work
41 Number of participants requiring additional medication
42 Number of participants with any adverse events
43 Adverse events description
44 Number of participants with irregular bleeding
45 Number of participants with headache
46 Number of participants with nausea
47 Number of participants with weight gain
48 Number of participants that withdrew
49 Number of participants that withdrew due to adverse events
50 Number of participants in safety analysis
51 Intension to treat analysis?

Appendix 7. Risk of bias assessment

• Sequence generation

Was sequence generation adequate (e.g. use of a random number table, a computer random number generator or coin tossing); inadequate (e.g. use of date of birth, or clinical record number); or unclear (insufficient information about the process of sequence generation)?

• Allocation concealment

Was allocation concealment adequate (e.g. use of central allocation or opaque sealed envelopes); inadequate (e.g. use of an open random allocation schedule, date of birth, or case record number); or unclear (insufficient information about the process of allocation concealment)?

• Blinding of participants, providers, and outcome assessors

Was blinding adequate (e.g. participants and researchers were all blinded and it was unlikely that blinding could have been broken, either participants or some researchers are not blinded but outcome assessment was blinded, or no blinding was used but this is not likely to influence outcomes); inadequate (e.g. no blinding or incomplete blinding and outcomes are likely to be influenced by this); or unclear (insufficient information about the process of blinding)?

• Incomplete outcome data

Was outcome data addressed adequately (e.g. there was no missing outcome data, reasons for missing outcome data were unlikely to be related to true outcome, or missing outcome data was balanced in numbers across intervention groups); inadequate (e.g. reasons for missing outcome data were likely to be related to true outcome); or unclear (insufficient information about the process of addressing outcome data)?

• Selective outcome reporting

Was the study free of selective reporting? Adequate (e.g. the study protocol is available and all pre‐specified outcomes have been reported, or the study protocol is not available but it is clear that all pre‐specified outcomes have been reported); inadequate (e.g. not all pre‐specified primary outcomes have been reported); or unclear (insufficient information about the process of outcome reporting).

• Sponsor bias

Was the study free of sponsor bias? Low risk (the study is unfunded or is not funded by a drug manufacturer); high risk (completely or partially funded by a drug manufacturer); or unclear (insufficient information about funding ).

Each of these domains were assessed as low risk, unclear (indicating an uncertain risk of bias), or high risk. No study was automatically excluded as a result of a rating of unclear or high risk. When it was unclear, study authors were contacted about the methods used, and any missing data was sought.

We completed the risk of bias assessment in theCharacteristics of included studies tables, including commentary about each of the domains, where possible. This led to an overall assessment of the risk of bias of included studies. A summary of the risk of bias table was added as a figure.

Comparison 1. Combined OCP versus placebo or no treatment.

Comparison 2. Combined low dose (ethinylestradiol (EE) 20–30 μg) OCP versus another combined low dose (EE 20–30 μg) OCP.

Comparison 3. Combined OCP versus non‐steroidal anti‐inflammatory drug (NSAID).

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

2023 update

The protocol stated that we would include studies that compared one oral contraceptive pill (OCP) with another. We chose to also include studies that compared different regimens of the same OCP, as this is important information to physicians and women. We introduced subgroups comparing the oestrogen dose and progestogen generation of the OCPs, as well as continuous regimen versus standard regimen.

We searched for unpublished studies using ClinicalTrials.gov in accordance with newer recommendations. We introduced GRADE in accordance with newer Cochrane recommendations. We added sponsor bias as it is an important factor in pharmaceutical trials.

We added newer generations of progestogen. We chose to report risk ratios, as odds ratios are difficult to interpret when there are many events.

We added two secondary outcomes: withdrawal from a trial and withdrawal owing to adverse events, as these are now seen as important.

2008 update

Restructured comparisons.

Changed outcome of pain relief to pain improvement.

Changed the title from 'Combined oral contraceptive pill (OCP) as treatment for primary dysmenorrhoea' to 'Oral contraceptive pill as treatment for primary dysmenorrhoea'. The original title was reinstated for the 2022 version.

Internal sources

• Faculty of Medical and Health Sciences, University of Auckland, New Zealand

  Editorial advice

• Hvidovre Hospital, Department of Gynecology and Obstetrics, Denmark

  Salary of Jeppe Bennekou Schroll from 2018 to 2022

External sources

• Princess of Wales Memorial Trust Fund administered by the Mercia Barnes Fund 1991 to 2002, New Zealand

  Salary support for author Chooi L Wong, for version published in 2001

References to studies included in this review

References to studies excluded from this review

References to ongoing studies

Additional references

References to other published versions of this review