Biphasic versus triphasic oral contraceptives for contraception

 

Abstract

Background

Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. A suggested disadvantage of biphasic compared to triphasic oral contraceptive (OC) pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage.

Objectives

To compare biphasic with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects.

Search methods

We searched MEDLINE, POPLINE, LILACS and CENTRAL, as well as clinical trials databases (ClinicalTrials.gov and ICTRP). We searched the reference lists of relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies.

Selection criteria

We included randomized controlled trials comparing any biphasic with any triphasic OC when used to prevent pregnancy.

Data collection and analysis

We examined the studies found during the searches for inclusion and assessed methodological quality. We contacted the authors of included studies and of possibly randomized studies for information about the methods and outcomes. We entered the data into RevMan. We calculated Peto odds ratios for incidence of discontinuation due to medical reasons, intermenstrual bleeding, and absence of withdrawal bleeding.

Main results

Only two trials of limited quality met our inclusion criteria. One study compared two biphasic pills and one triphasic pill, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. The other trial compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and with another triphasic containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic. The odds ratio of cycles with intermenstrual bleeding was 1.70 (95% confidence interval (CI) 1.29 to 2.24) for the biphasic compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.48 (95% CI 3.13 to 13.39). In contrast, cycle control with the biphasic pill was comparable to that of the triphasic containing the same progestin (norethindrone).

Authors' conclusions

The available evidence is limited and the internal validity of these trials is questionable. Given the high losses to follow up, these reports may even be considered observational. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. The choice of progestin may be more important than the phasic regimen in determining bleeding patterns.

 

Plain language summary

Birth control pills with two phases versus three phases

Side effects of birth control pills may keep women from using them as planned. Attempts to decrease side effects led to the three-phase pill in the 1980s. Pills with phases provide different amounts of hormones over three weeks. Whether three-phase pills lead to fewer pregnancies than two-phase pills is unknown. Nor is it known if the pills give better cycle control or have fewer side effects. This review looked at whether two-phase pills worked as well as three-phase pills. We also studied whether women had fewer side effects with these pills.

We did a computer search for studies of birth control pills with two phases versus pills with three phases. We also wrote to researchers and manufacturers to find other trials. We included randomized trials in any language.

We found only two trials that looked at two-phase versus three-phase birth control pills. The studies did not have good methods and the authors did not report all their methods. Many women dropped out of the studies, which affects what can be said about the results. One study compared two types of two-phase pills with a three-phase pill. The pills did not differ in any major ways, including the numbers of women who stopped using the pills due to health problems. The other trial compared a two-phase pill with two different three-phase pills. The two-phase pill had worse bleeding patterns than the three-phase pill with a different hormone (levonorgestrel). In contrast, bleeding with the two-phase pill was like that of the three-phase pill with the same hormone (norethindrone). The type of hormone may be more important than the phases for cycle control.

These trials did not provide enough evidence to say if three-phase pills worked any better than two-phase types for birth control, bleeding patterns, or staying on the pill. More research would be needed to show whether three-phase pills were better than two-phase pills. However, two-phase pills are not used enough to justify further research.

 

摘要

背景

雙相式與三相式口服避孕藥之比較

口服避孕藥所造成的副作用會使患者不想使用或停止使用，雙相式跟三相式的口服避孕藥相比會增加點狀出血的機會。我們針對增加點狀出血這項潛在性的缺點進行了系統性研究

目標

比較雙相式與三相式口服避孕藥之效用、對周期的控制、以及因副作用而停藥的比率

搜尋策略

我們搜尋了MEDLINE、EMBASE、 POPLINE、LILACS、和CENTRAL等，我們也搜尋了有關文章和書籍相關章節的參考文獻，我們還聯繫了在歐洲和美國的相關研究作者和製藥公司。

選擇標準

我們納入了比較任何兩相式與任何三相式口服避孕藥來預防懷孕的隨機對照試驗

資料收集與分析

我們用考科藍實證醫學的指引方針來審查搜索到的研究，包括了質、量和評估方法等。 我們與研究本身和其他隨機研究的作者連絡，看能否提供給額外的資訊。我們把數據輸入RevMan 。我們計算了因其他醫學原因、周期間出血、無停藥後出血而停用避孕藥的Peto勝算比率

主要結論

只有兩篇研究達到我們的納入標準。 1978年的Larranaga比較兩種雙相式和一種三相式的避孕藥丸，每個皆含有levonorgestrel and ethinyl estradiol，結果發現三種避孕藥停藥的頻率沒有出現重要的不同，PercivalSmith在1990年比較了含norethindrone(ortho 10/11)的雙相口服避孕藥和含有levonorgestrel(Triphasil)的三相避孕藥以及與其他含norethindrone(ortho 7/7/7)的三相避孕藥。雙相式避孕藥對週期的控制比含levonorgestrel的三相式避孕藥差。兩者周期間出血的勝算比率為為1.7 (95 ％ CI為1.3到2.2)，不出現撤出性出血的週期勝算比率為6.5(95％ CI為3.1至13)。相對的，若雙相式與三相式若含有相同的黃體素(norethindrone)則沒有差異 。

作者結論

現有的證據是有限的，而這些試驗內部效度令人懷疑；由於很難進行後續追蹤，因此有些還可能僅會被視為觀測性的報告。但雙相式避孕藥對週期的控制比含有levonorgestrel的三相式避孕藥仍比較屈於劣勢，所以選擇避孕藥中所含的黃體素的種類可能比選擇幾相式的避孕藥更重要。

翻譯人

本摘要由臺灣大學附設醫院林思宏翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

雙相式與三相式的避孕藥 避孕藥的副作用會使婦女不去計劃使用它們。為了試圖減少避孕藥所導致的副作用1980年開始使用三相式避孕藥。多相式避孕藥於使用的三個星期提供不同劑量的賀爾蒙，是否三相避孕藥比雙相式藥丸更有效的減少懷孕目前仍不得而知。也不知道是不是有更好地週期控制或有較少的副作用。本篇回顧看是否雙相藥丸跟三相藥丸效用相同。我們還研究了使用三相避孕藥的婦女是否有較少的副作用。我們用電腦搜尋了比較兩者之間控制懷孕的情形，我們還寫信給研究人員和製造商尋求其他的相關研究。我們納入了任何語言的隨機試驗，我們發現只有兩篇研究比較雙相和三相避孕藥。這些研究沒有很好的方法或作者沒有報告全部的研究方法。許多婦女離開了所做的研究，從而影響到可能得到的結果。一項研究比較兩種類型的兩相式藥丸和三相式藥丸。發現在主要的項目上沒有不同，包括因健康問題停止使用避孕藥的婦女人數。另一項研究比較兩相式藥丸與兩種不同的三相式藥丸：與不同黃體激素(levonogestrel)的三相式藥丸相比，兩相式藥丸出現比較差的出血模式。相對的，若雙相式與三相式藥丸若含有相同的黃體素(norethindrone)則沒有差異。避孕藥中所含的黃體素的種類可能比選擇幾相式的避孕藥更重要。因此目前沒有提供足夠的證據說三相式避孕藥在節育、出血模式、或長期使用避孕藥等各方面比雙相式的避孕藥好。需要更多的研究看是否三相避孕藥優於兩相式的避孕藥。但是，兩相式的避孕藥沒有足夠的理由進一步研究。