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A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive

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Abstract

Introduction

The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns.

Objective

This systematic review and meta-analysis aimed to summarize current evidence regarding the adverse events, and their prevalence, reported during the use of oral levonorgestrel emergency contraceptives.

Methods

Four electronic databases and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched. Studies that reported or investigated safety outcomes or adverse reactions during the use of levonorgestrel as an emergency oral contraceptive were included. Data on study design, demographics of levonorgestrel and the control cohort, and reported adverse effects were extracted.

Results

A total of 47 articles were included in this systematic review, from which it was shown that most of the adverse reactions were common and not serious. Uncommon adverse reactions identified included anorexia, ectopic pregnancy, exanthema, chloasma, miscarriage, and weight gain. Multiple serious adverse events, including convulsion, ectopic pregnancy, febrile neutropenia, stroke, abdominal hernia, anaphylaxis, cancer, ovarian cyst rupture, serious infections, and suicidal ideation, were reported. In addition, the prevalence of adverse events after a levonorgestrel 0.75 mg two-dose regimen and a levonorgestrel 1.5 mg single-dose regimen were not statistically different (p > 0.05).

Conclusions

The most common adverse effects of levonorgestrel were not serious. This systematic review shows that data regarding the adverse reactions of repeated use of levonorgestrel are scarce. Studies on the multiple uses of levonorgestrel emergency contraception are still required to ensure its safety.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, Thailand

    Nattawut Leelakanok

  2. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Pharmacokinetic Research Unit, Naresuan University, Phitsanulok, Thailand

    Janthima Methaneethorn

  3. Center of Excellence for Environmental Health and Toxicology, Naresuan University, Phitsanulok, Thailand

    Janthima Methaneethorn

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  1. Nattawut Leelakanok
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NL and JM designed the research and conducted the systematic review and meta-analysis. NL wrote the paper and had primary responsibility for the final content. Both authors read and approved, and are in agreement with, the final version submitted for publication. The content has not been published elsewhere.

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Correspondence to Nattawut Leelakanok.

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This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

Nattawut Leelakanok and Janthima Methaneethorn declare they have no conflicts of interest.

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Leelakanok, N., Methaneethorn, J. A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive. Clin Drug Investig 40, 395–420 (2020). https://doi.org/10.1007/s40261-020-00901-x

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