Safety of hormonal contraception among women with sickle cell disease: An updated systematic review

To update a previous systematic review on sickle cell disease (SCD) and adverse health outcomes associated with hormonal contraception (HC) use.

We searched multiple databases for articles from inception through December 12, 2022. We included articles that assessed risk of adverse health outcomes (e.g., thrombosis, painful episodes, osteoporosis) among women with SCD using any HC method. We assessed risk of bias for each study and certainty of evidence for all outcomes.

Nine articles met inclusion criteria; four were new. Eight studies had high risk of bias and one had moderate risk. Three studies examined thrombosis among HC users with SCD; one found that 2.9% of 67 women using combined oral contraception (COC) and none of 84 women using other HC methods experienced venous thromboembolism (VTE), another found no VTE among 20 HC users, and another found elevated risk of ischemic stroke among oral contraception users (presumed mostly COC) versus non-users (adjusted hazards ratio 3.6, 95% confidence interval 0.8-16.5). Six studies with disparate study methods generally found that HC users did not report increases in painful episodes, and in some studies but not all, use of progestin-only methods appeared to decrease painful episodes. One study found no differences in bone mineral density between HC users and non-users with SCD, and another found no diagnoses of osteopenia among 20 HC users with SCD.

Evidence remains limited for adverse health outcomes, especially thrombosis, with HC use among women with SCD. The certainty of evidence was low for all outcomes.

Sickle cell disease (SCD) increases risk for stroke, venous thromboembolism, and pregnancy complications. Access to safe contraception is essential for women with SCD who are at risk for and do not desire pregnancy or who wish to optimize pre-pregnancy health. This updated review can help providers counsel patients with SCD about safe use of contraception.