Abstract
OBJECTIVES: To systematically review literature on whether hormonal contraception following ulipristal acetate (UPA) for emergency contraception decreases the effectiveness of either drug. STUDY DESIGN: We searched multiple databases through December 2022 for studies assessing the interaction between UPA and hormonal contraception. The primary outcome was contraceptive effectiveness, measured by pregnancy rates or proxy measures (e.g., ovarian activity). We extracted and summarized findings from identified studies, assessed risk of bias for each study, and determined certainty of evidence for all outcomes. RESULTS: Four studies met inclusion criteria; all had low risk of bias. Two studies assessed whether UPA use affected the ability of oral contraceptives (OCs) to inhibit ovulation; no differences were observed in ovarian activity when starting OCs 1 day after UPA compared with starting OCs 1 day after placebo. Two studies assessed whether OC use affected the ability of UPA to delay ovulation; both studies observed higher proportions of ovulation when UPA was followed by OC use versus delayed or no OC use. One study assessed ovulation risk when UPA was taken after missed OCs, followed by immediate versus delayed OC resumption; no ovulations occurred within the first 5 days after UPA administration in either group, but there was greater risk of ovulation beyond 5 days with delayed versus immediate OC resumption. CONCLUSIONS: While there is no evidence that UPA affects the ability of hormonal contraception to inhibit ovulation, hormonal contraception use immediately or soon after UPA may decrease UPA's ability to delay ovulation. The certainty of evidence ranged from moderate to very low. IMPLICATIONS: If a patient desires hormonal contraception after UPA, an interaction can be avoided by delaying initiation or resumption of hormonal contraception. The risk of pregnancy due to decreased UPA effectiveness with immediate hormonal contraception should be balanced against the risk of subsequent pregnancy due to delay or non-start of hormonal contraception.