The effect of multivitamin supplements on continuation rate and side effects of combined oral contraceptives: A randomised controlled trial

Abstract

Objectives This study aimed to assess the effect of multivitamin use during the pill-free interval on the continuation rate and side effects of combined oral contraceptives (COCs) within the first few cycles of use.

Methods In this trial, 332 women presenting to public health centres in an Iranian city each received a COC pack containing 21 pills and were randomised to one of three groups: two of the groups also received 42 multivitamin pills or 42 placebo pills to be taken once a day for 7 days before starting COCs and again during the 7-day pill-free interval for five cycles, while the third group received no multivitamin or placebo pills with their COCs. The groups were compared using Cox regression and χ² tests.

Results There were no losses to follow-up. Continuation rates at the sixth cycle were 88% for the multivitamin group, 75% for the placebo group and 67% for the no intervention group. Compared with the multivitamin group, the six-cycle discontinuation rate was significantly higher in the placebo group (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.15–4.45; p = 0.019) and no intervention group (HR 3.15, 95% CI 1.66–5.99; p < 0.001). Nausea, mood changes, weight gain and breast tenderness were significantly less common in the multivitamin group than in the other groups in all cycles, and spotting/irregular bleeding and dizziness were significantly less common in most of the second, third and sixth cycle follow-up.

Conclusions Multivitamin supplements could significantly reduce the side effects of COCs in the initial cycles and improve continuation rates. However, the study limitations do not allow for any definite conclusion for their use in clinical practice, especially in communities rich in nutrients.

Chinese Abstract

摘要

目的：本研究旨在评估在不服避孕药的间歇期口服多种维生素对续用率的影响，及服用复方避孕药（COCS）最初几个周期的副作用。

方法：在这项试验中，在伊朗城市代表公众健康中心的332名女性均收到含有21粒药物的复方口服避孕药包，并被随机分到3组。其中2组的妇女还分别收到了42粒维生素或42粒安慰剂，这些药物需要在服用口服避孕药之前及不同周期的间歇期内每天服用1次，连续服用7天；第三组只有复方口服避孕药。不同组之间用COX回归及卡方检验进行比较。

结果：目前还没有丢失的随访。三个组在第六个周期的续用率分别为：口服维生素组88%，口服安慰剂组75%，无干预组67%。与口服多种维生素组比较，口服安慰剂组在第六周期的停药率明显高（HR2.26，95%CI1.15-4.45;p=0.019），无干预组的停药率也明显高于口服维生素组（HR 3.15, 95% CI 1.66 − 5.99; p = 0.001）。在所有周期中，恶心、情绪变化、体重增加及乳房触痛在维生素组明显少于其他2组，瘀点、不规则出血、眩晕在第二、三、六周期很少见。

结论：多种维生素的应用可以显著降低开始口服复方避孕药的最初几个周期内的副作用，同时可以提高续用率。然而，由于这篇文章的限制，并无明确结论支持他们广泛应用于临床，尤其是在有丰富营养物质的社区。

关键词：副作用，复方口服避孕药，续用率，维生素

KEYWORDS:

• Adverse effects
• Combined oral contraceptives
• Continuation rate
• Vitamins

ACKNOWLEDGEMENTS

The authors extend their gratitude to those who helped with data collection and the women who participated in the study and provided the necessary information. Also, the authors gratefully thank the Iran Virayesh Center for editing of this manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This research was approved by the Students’ Research Committee and financially supported by the deputy of research at Tabriz University of Medical Sciences, Tabriz, Iran. No financial support was given by any pharmaceutical company.