Elsevier

Contraception

Volume 85, Issue 6, June 2012, Pages 527-537
Contraception

Review article
Contraception for individuals with sickle cell disease: a systematic review of the literatureā˜†

https://doi.org/10.1016/j.contraception.2011.10.008Get rights and content

Abstract

Background

Women with sickle cell disease have an increased risk of pregnancy-related complications and need safe, effective contraceptive methods to prevent unintended pregnancy.

Study Design

We conducted a systematic review to examine the safety of hormonal and intrauterine contraceptive use among women with sickle cell disease.

Results

Eight articles met the inclusion criteria. The evidence was of fair to poor quality and suggested that progestin-only and combined hormonal contraception had no effect on frequency of sickle crises or other adverse events and no effect on hematologic parameters associated with sickle crises. No studies examined the risk of thromboembolism in combined hormonal contraceptive users with sickle cell disease. There was insufficient evidence to comment on the safety of intrauterine contraception.

Conclusion

While data are limited, there is no evidence to suggest that hormonal contraceptive use among women with sickle cell disease is associated with an increased risk of clinical complications.

Introduction

In the United States, sickle cell disease (also known as sickle cell disorder or sickle cell anemia) affects an estimated 70,000 to 100,000 Americans [1]. Sickle cell disease refers to a group of inherited hemoglobin disorders that cause a defect in red blood cells associated with increased rates of hemolysis and cell sickling. Chronic hemolysis is associated with a variety of laboratory abnormalities including anemia, reticulocytosis and elevated fetal hemoglobin. Red blood cell sickling can lead to venous stasis, blood hyperviscosity, vaso-occlusion and tissue infarction. Vaso-occlusion results in recurrent painful ā€œsickle crisesā€ and a variety of serious end-organ system complications including retinopathy, stroke, nephropathy and acquired asplenia with a subsequent increase in susceptibility to infection [2], [3]. Women with sickle cell disease have poor pregnancy-related outcomes, with higher rates of intrauterine fetal demise, intrauterine growth restriction, preterm birth, hypertensive disorders and cesarean delivery than women without sickle cell disease [4], [5], [6], [7]. In addition, during pregnancy, women with sickle cell disease experience an increased risk of sickle crisis and clinically significant anemia than women without sickle cell disease [8].

Contraceptive use is an important strategy for reducing the risk of unintended pregnancy. However, among women with complex medical conditions such as sickle cell disease, confusion due to a lack of compiled evidence on the safety of the various contraceptive options may unnecessarily limit contraceptive use. One concern is the potential for an increased risk of venous thromboembolism (VTE) among women with sickle cell disease who use combined hormonal contraception. Combined hormonal contraceptive use is a risk factor for VTE in healthy women, with an increased relative risk of about 2 compared with nonusers, translating to a low absolute risk of about 9ā€“10 events per 10,000 users per year [9]. Among patients with sickle cell disease, the coagulation system is activated with increased circulating tissue procoagulant factor, increased markers of thrombin generation, decreased levels of natural anticoagulant proteins, and evidence of platelet and fibrinolytic system activation. Several studies have documented that individuals with sickle cell disease have a chronically activated coagulation system [10], [11], [12], leading to an increase in the risk of VTE among individuals with sickle cell disease compared with healthy patients; however, the exact risk is unclear [13], [14]. Given the increased risk for VTE among healthy individuals on combined hormonal contraceptives and this potential for increased VTE with sickle cell disease, there is a theoretical concern that the interaction will lead to a further increased risk for VTE for sickle cell disease patients who use combined hormonal contraceptives.

There is also concern that hormonal contraception may increase the risk of sickle cell crises [15], [16]. Increased platelet aggregation, noted to occur with hormonal contraceptives, also occurs in association with vaso-occlusive crises [17], [18], although the degree to which hypercoagulability contributes to vaso-occlusion or results from vascular injury associated with the crises is unclear. Additionally, decreased red blood cell deformability precedes the onset of a vaso-occlusive crisis where increased deformability accompanies resolution of the pain [19]. There are some data suggesting that steroids from combined hormonal contraceptives may interact with the red blood cell membrane leading to decreased erythrocyte deformability [20]. Other studies have found no significant difference in red blood cell deformability among combined oral contraceptive (COC) users and nonusers [21], [22]. Alternatively, there is some evidence that progesterone may stabilize the erythrocyte membrane and therefore may actually be beneficial in preventing sickle crises [23], [24], [25].

The objective of this review is to determine from the literature whether women with sickle cell disease who use hormonal contraceptive methods or intrauterine devices (IUDs) have an increased risk of adverse outcomes, such as increases in sickle cell crises and VTE, compared with women with sickle cell disease who do not use hormonal contraceptives or IUDs. One prior systematic review of progestin-only contraceptive methods concluded that, despite limited data, progestin-only methods were safe for use among women with sickle cell disease [26]. Similarly, a Cochrane review [27] of randomized controlled trials evaluating all forms of hormonal contraception concluded that the data, which were limited, suggested that depomedroxyprogesterone acetate (DMPA) is safe and may reduce sickle pain crises in subjects with sickle cell disease. In this review, we have included more recent literature and expanded the review to include studies that examined the use of combined hormonal contraceptives and IUDs among women with sickle cell disease.

Section snippets

Materials and methods

We searched PUBMED to identify manuscripts published in peer-reviewed journals in all languages from 1966 through March 2011 using the search strategy in Appendix A. We also searched the reference lists of relevant articles identified by the electronic search. The objective of the search was to identify studies that examined health outcomes among women with sickle cell disease who were using hormonal contraceptives or intrauterine contraceptives.

Results

The search strategy identified 162 articles of which nine met our criteria for inclusion in this review [30], [31], [32], [33], [34], [35], [36], [37], [38]. The progestin-only studies included one randomized controlled trial [31], two nonrandomized controlled trials [34], [35], two prospective descriptive studies[33], [38] and four cross-sectional studies [30], [32], [36], [37]. The combined hormonal contraceptive studies included one nonrandomized controlled trial [34] and four

Discussion

Overall, evidence suggests that hormonal contraceptive methods do not increase the frequency or severity of sickle cell crises and are not associated with an increased risk of adverse events. Use of progestin-only contraception did not increase the risk for sickle cell crises or other clinical adverse events and, in some cases, appeared to decrease the risk of painful episodes. These results are supported by the studies examining surrogate markers where hematologic parameters were either the

Summary

Data are limited and of fair to poor quality, but overall, there is no evidence to suggest that hormonal contraceptive method use among women with sickle cell disease is associated with an increased risk of clinical complications such as sickle cell crises. Further examination to determine whether combined hormonal contraceptive use increases the risk of VTE in women with sickle cell disease relative to women without sickle cell disease is needed. As sickle cell disease is associated with

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      The principal concern is the potential for an increased risk of venous thromboembolism (VTE), due to a chronically activated coagulation system in sickle cell disease patients [381ā€“383]. However, there is no clear evidence to suggest that hormonal contraceptive use is associated with an increased risk of complications in women with sickle cell disease [384,385]. Therefore, the WHO currently classifies sickle cell disease as a Category 2 for combined oral contraceptives, meaning that the benefits of combined oral contraceptives use among women with this condition generally outweigh the theoretical or proven risks [386].

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    ā˜†

    The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. There was no funding for this review.

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