Elsevier

Contraception

Volume 97, Issue 6, June 2018, Pages 478-489
Contraception

Review article
The relationship between progestin hormonal contraception and depression: a systematic review

https://doi.org/10.1016/j.contraception.2018.01.010Get rights and content

Abstract

Objective

We performed a systematic review to look for an association between progestin-only contraception and depression.

Methods

We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders.

Results

We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression.

Conclusion

Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).

Introduction

Sexually active women of reproductive age who want to prevent pregnancy need reliable contraceptive options. Decisions about which method to choose may involve factors such as efficacy, medical problems, previous experiences with side effects or failures, or concerns about imperfect compliance. Due to the risks or side effects of estrogen, many women choose a hormonal contraceptive that is formulated only with progestin. Even with limited progestin exposure, concerns exist about side effects including weight gain, acne, mood changes and depression. Depression side effects of progestin contraception have been stressed in the lay press and are common patient concerns [1], [2]. Depression is also a concern for women considering hormonal contraception due to female population prevalence. The major depression lifetime prevalence for US women is 7.4/100, twice that of men [3]. Concerns about progestin's influence on mood are based on clinical experience and basic science research [4], [5].

Concerns about progestin-related depression effects also arise from early clinical data on depot medroxyprogesterone acetate (DMPA), which was approved for use as a long-acting contraceptive in 1992 by the Food and Drug Administration (FDA). The package labeling stated that women with depression should be observed carefully, and additional administration should not be performed if depression recurred. This concern was based on FDA clinical data showing that 1.5% of 4200 users reported depression and 0.5% discontinued their use of DMPA for this reason [6]. Since then, many studies have sought an answer to whether DMPA may cause depression.

The relationship between progestin-only contraceptives and depression remains unclear. This study aims to systematically review the medical literature regarding this relationship, additionally including generalized and postpartum depression, as well as adolescents.

Section snippets

Methods

We conducted this systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [7]. Prior to conducting our literature review, we identified the following questions to guide our search:

  • 1.

    Is there an association or causative link between progestin-only hormonal contraception and depression effects in human females?

  • 2.

    Does the type of progestin or route of administration influence such an association?

  • 3.

    Are there certain populations (such as adolescents,

Study selection

Our search used multiple title and abstract searches plus PubMed MESH search terms including “medroxyprogesterone depression” with 155 abstracts, “levonorgestrel depression” with 80 abstracts, “norethindrone depression” with 126 abstracts, “etonorgestrel depression” with 8 abstracts, “Progestin [AND] depression [AND] contraception” with 190 abstracts and “progestin [AND] postpartum depression” with 78 abstracts. This initially yielded 2305 citations and, once exclusion criteria were applied,

Conclusions

In summary, it is difficult to draw firm conclusions about the relationship between progestin-only hormonal contraception and depression. The data thus far do not support a clear, general relationship between progestin contraceptives and depression scores or incident depression diagnoses.

Several limitations exist in assessing the link between progestin-only hormonal contraception and depression. The trials that use validated measures of depression symptoms use a variety of scales, some of which

Funding

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

References (40)

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