Comparison of Combined Parenteral and Oral Hormonal Contraceptives: A Systematic Review and Meta-Analysis of Randomized Trials

Background: Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. Objectives: To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. Methods: We performed a systematic literature search in four medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus-from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Results: Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = -0.06, CI: -0.66-0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (chi 2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (chi 2 = 19.04, p =0.001, I2 = 80%), nausea (chi 2 = 8.04, p =0.005, I2 = 75%), and vomiting (chi 2 = 9.30, p =0.002; I2 = 72%). Conclusion: Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence.