Effect of contraceptive methods on the vaginal microbiome and host immune factors.

Jennifer Deese, Katherine Spaine, Florence L D'Hellencourt, Laahirie Edupuganti, Veronique C Bailey, Lindi Masson, Bin Zhu, David Edwards, Khatija Ahmed, Mags Beksinska, Charles S Morrison, Kavita Nanda, Rushil Harryparsad, Gregory A Buck, Myrna G Serrano, Kimberly K Jefferson, Jerome F Strauss Iii, Jennifer Smit, Nina Radzey, Celia Mehou-Loko, Anna-Lise Williamson, Ongeziwe Taku, Bahiah Meyer

Journal: Contraception 2025;148():110936

PMID: 40345368

Abstract

OBJECTIVE

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.

Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

Address: Microbiology and Immunology Department, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA; Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond, VA, USA.; Microbiology and Immunology Department, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA; Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond, VA, USA; Statistical Science, College of Humanity and Sciences, Virginia Commonwealth University, Richmond, VA, USA.; Setshaba Research Centre, Tshwane, South Africa; Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.; Setshaba Research Centre, Tshwane, South Africa.; MatCH Research Unit (MRU), University of the Witwatersrand, Durban, South Africa.; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa.; FHI 360, Cary, NC, USA.; Department of Obstetrics and Gynecology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa; Centre for the AIDS Programme of Research in South Africa, Durban, South Africa; Central Clinical School, Monash University, Melbourne, Australia.; Microbiology and Immunology Department, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA; Center for Microbiome Engineering and Data Analysis, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: [email protected].
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