Serrano, Myrna G.Edwards, DavidAhmed, KhatijaBailey, Veronique C.Beksinska, MagsEdupuganti, LaahirieHarryparsad, RushilD'Hellencourt, Florence L.Meyer, BahiahMehou-Loko, CeliaRadzey, NinaTaku, OngeziweWilliamson, Anna-LiseSmit, JenniferSpaine, KatherineZhu, BinJefferson, Kimberly K.Nanda, KavitaStrauss III, Jerome F.Morrison, Charles S.Deese, Jennifer; Masson, Lindi; Buck, Gregory A.Deese, JenniferMasson, LindiBuck, Gregory A.2025-11-202025-11-202025-08Serrano, M.G., Edwards, D., Ahmed, K. et al. 2026, 'Effect of contraceptive methods on the vaginal microbiome and host immune factors', Contraception, vol. 148, art. 110936, pp. 1-8, doi : 10.1016/j.contraception.2025.110936.0010-7824 (print)1879-0518 (online)10.1016/j.contraception.2025.110936http://hdl.handle.net/2263/105394OBJECTIVE : The objective of this study was to assess alterations in vaginal microbiota and immune markers over the first 3 months following initiation of copper intrauterine device (copper IUD), levonorgestrel (LNG) implant, and intramuscular depot medroxyprogestone acetate (DMPA-IM). STUDY DESIGN : We included 162 participants from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, which enrolled healthy, HIV-negative women seeking contraception and randomized them to a copper IUD, LNG implant, or DMPA-IM. Microbiome and immune profiles in vaginal swab samples collected at enrollment, 1 month and 3 months were analyzed. We categorized microbiome profiles as ‘‘optimal’’, ‘‘intermediate’’, or ‘‘non-optimal’’ based on established criteria [1]. We compared microbiome and immune markers across contraceptive groups and evaluated changes to 1 and 3 months. RESULTS : Copper IUD users had a more diverse vaginal microbiome and generally increased inflammatory cytokines and antimicrobial peptides over the 3-month follow-up, compared to LNG-implant and DMPA-IM users [2]. LNG-implant users had less complex vaginal microbiomes with reduced inflammation, while DMPA-IM showed little change in either microbiome composition or inflammatory markers. Copper IUD users exhibited lower microbiome stability and a higher likelihood of transitioning to less optimal profiles. In contrast, LNG-implant users showed greater stability and a higher probability of transition to optimal microbiome and immune marker profiles. CONCLUSIONS : Contraceptive methods affect the vaginal microbiome differently. Copper IUD use may lead to less favorable profiles and increased levels of some immune markers, indicating potential adverse health effects. Conversely, LNG-implant usage promotes a more favorable microbiome and immune marker balance. IMPLICATIONS : Our findings suggest that copper IUDs are associated with decreased prevalence of Lactobacillus-dominated microbiomes, higher transition rates towards less optimal microbiome and increased inflammatory profiles, which may lead to negative implications for gynecologic and reproductive health, the LNG-implant may offer positive health benefits with increased prevalence of L. crispatus-dominated microbiomes.en© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Copper intrauterine device (copper IUD)InflammationImplant, and intramuscular depot medroxyprogestone acetate (DMPA-IM)LactobacillusLNG-implantVaginal microbiomeLevonorgestrel (LNG)Article