Pil kontraseptif oral gabungan untuk dismenorea primer
Abstract
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.
PICOs
Ringkasan bahasa mudah
Pil kontraseptif oral gabungan (OCP) sebagai rawatan untuk dismenorea primer
Soalan ulasan
Pengarang Cochrane menyemak bukti tentang keberkesanan dan keselamatan pil kontraseptif oral gabungan (OCP) untuk rawatan senggugut yang menyakitkan (sakit haid, juga dipanggil dismenorea).
Latar belakang
OCP sedia digunakan sebagai rawatan untuk senggugut, tetapi bukti tentang kesannya tidak pasti.
Ciri‐ciri kajian
Kami mendapati 21 kajian rawak terkawal (kajian klinikal di mana orang ramai dimasukkan ke dalam satu daripada dua atau lebih kumpulan rawatan secara rawak) yang membandingkan kesan OCP dengan sama ada plasebo (pil palsu), OCP lain atau ubat anti‐radang bukan steroid yang mengurangkan sakit dan keradangan. Kajian tersebut melibatkan 3723 wanita. Kebanyakan wanita mengalami senggugut yang menyakitkan sekurang‐kurangnya tahap sederhana. Pengilang OCP membiayai 11 kajian. Kami mencari pangkalan data pada Mac 2023.
Keputusan utama
OCPs dibandingkan dengan plasebo
OCP mengurangkan kesakitan sebanyak 0.7 hingga 1.3 mata pada jumlah skala dismenorea (julat 0 hingga 6) daripada plasebo pada wanita yang mengalami senggugut (6 kajian dengan 588 wanita; bukti berkualiti tinggi). Enam kajian yang mengukur peningkatan sebagai kategori ya/tidak menunjukkan bahawa OCP boleh mengurangkan kesakitan. Wanita dengan peluang 28% untuk keberkesanan dengan plasebo mungkin mempunyai peluang 37% hingga 60% untuk keberkesanan dengan OCP (bukti berkualiti rendah).
OCP meningkatkan risiko kesan sampingan (59% dalam kumpulan plasebo berbanding 71% hingga 86% dalam kumpulan OCP; bukti berkualiti sederhana), dan boleh membawa kepada kesan sampingan yang lebih serius (1.1% dalam kumpulan plasebo berbanding 0.5% hingga 6.8 % dalam kumpulan OCP; bukti berkualiti rendah).
Pendarahan tidak teratur meningkat dalam kalangan wanita yang menggunakan OCP. Wanita dengan placebo mempunyai 18% risiko pendarahan tidak teratur manakala 39% hingga 60% risiko pendarahan tidak teratur dengan OCP (bukti berkualiti tinggi). Bukti kualiti sederhana mendapati bahawa OCP mungkin meningkatkan risiko sakit kepala (17% dalam kumpulan plasebo berbanding 19% hingga 35% dalam kumpulan OCP), dan loya (merasa sakit; 10% dalam kumpulan plasebo berbanding 11% hingga 22% dalam kumpulan OCP).
Kami tidak pasti tentang kesan OCP terhadap penambahan berat badan.
Bukti berkualiti rendah mendapati bahawa OCP mungkin mengurangkan sedikit keperluan untuk ubat tambahan (38% dalam kumpulan plasebo berbanding 15% hingga 37% dalam kumpulan OCP), dan ketiadaan kerja (36% dalam kumpulan plasebo berbanding 11% hingga 35% dalam kumpulan OCP).
OCP yang berbeza berbanding satu sama lain
Mungkin terdapat sedikit atau tiada perbezaan antara OCP yang mengandungi dos rendah atau tinggi estrogen, atau antara formulasi OCP yang lebih baru dan lebih lama (bukti berkualiti sederhana).
Menggunakan OCP berterusan (tiada pil tidak aktif diambil sebagai rehat antara pil aktif, untuk menangguh pendarahan) mungkin lebih banyak mengurangkan kesakitan berbanding rejimen tradisional (bukti berkualiti rendah). Regimen tradisional adalah mengambil tablet aktif selama 21 hari dan berhenti seketika selama 7 hari (atau mengambil jadual tidak aktif selama 7 hari) di mana pendarahan terobosan biasanya akan berlaku.
Mungkin terdapat sedikit atau tiada perbezaan dalam risiko sebarang kesan sampingan antara rejimen berterusan dan tradisional (65% dalam kumpulan tradisional berbanding 66% hingga 80% dalam kumpulan berterusan; bukti berkualiti rendah).
Disebabkan oleh bukti kualiti yang sangat rendah, kami tidak pasti jika terdapat perbezaan dalam risiko kesan sampingan yang serius (0.9% dalam kumpulan tradisional berbanding 0.3% hingga 7.7% dalam kumpulan berterusan), sakit kepala (8% dalam kumpulan tradisional berbanding dengan 4% hingga 15% dalam kumpulan berterusan), loya (6% dalam kumpulan tradisional berbanding 3% hingga 13% dalam kumpulan berterusan) atau tidak hadir bekerja (9% dalam kumpulan tradisional berbanding 6% hingga 18% dalam kumpulan berterusan). Penggunaan berterusan OCP mungkin meningkatkan pendarahan tidak teratur (33% dalam kumpulan tradisional berbanding 38% hingga 56% dalam kumpulan berterusan; bukti berkualiti sederhana).
Kajian ini tidak melaporkan tentang penambahan berat badan atau keperluan untuk ubat tambahan.
OCP berbanding dengan ubat anti‐radang bukan steroid
Disebabkan bukti berkualiti rendah, kami tidak dapat menentukan sama ada OCP lebih berkesan daripada ubat anti‐radang bukan steroid. Kesan sampingan tidak dilaporkan.
Kualiti bukti
Kualiti bukti adalah pelbagai dari sangat rendah hingga tinggi. Masalah yang paling penting ialah kekurangan data dan variasi data antara kajian.
