Copper intrauterine device increases vaginal concentrations of inflammatory anaerobes and depletes lactobacilli compared to hormonal options in a randomized trial

Bryan P. Brown (), Colin Feng, Ramla F. Tanko, Shameem Z. Jaumdally, Rubina Bunjun, Smritee Dabee, Anna-Ursula Happel, Melanie Gasper, Donald D. Nyangahu, Maricianah Onono, Gonasagrie Nair, Thesla Palanee-Phillips, Caitlin W. Scoville, Kate Heller, Jared M. Baeten, Steven E. Bosinger, Adam Burgener, Jo-Ann S. Passmore, Renee Heffron and Heather B. Jaspan ()
Additional contact information
Bryan P. Brown: Seattle Children’s Research Institute
Colin Feng: Seattle Children’s Research Institute
Ramla F. Tanko: University of Cape Town
Shameem Z. Jaumdally: University of Cape Town
Rubina Bunjun: University of Cape Town
Smritee Dabee: Seattle Children’s Research Institute
Anna-Ursula Happel: University of Cape Town
Melanie Gasper: Seattle Children’s Research Institute
Donald D. Nyangahu: Seattle Children’s Research Institute
Maricianah Onono: Kenya Medical Research Institute
Gonasagrie Nair: Desmond Tutu HIV Centre
Thesla Palanee-Phillips: Wits Reproductive Health and HIV Institute
Caitlin W. Scoville: University of Washington
Kate Heller: University of Washington
Jared M. Baeten: University of Washington
Steven E. Bosinger: Yerkes National Primate Research Center
Adam Burgener: Case Western Reserve University
Jo-Ann S. Passmore: University of Cape Town
Renee Heffron: University of Washington
Heather B. Jaspan: Seattle Children’s Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays. Primary endpoints include incident BV occurrence, bacterial diversity, and bacterial and cytokine concentrations. Secondary endpoints are bacterial and cytokine concentrations associated with later HIV seroconversion. Participants randomized to Cu-IUD exhibit elevated bacterial diversity, increased cytokine concentrations, and decreased relative abundance of lactobacilli after one and six months of use, relative to enrollment and other contraceptive options. Total bacterial loads of women using Cu-IUD increase 5.5 fold after six months, predominantly driven by increases in the concentrations of several inflammatory anaerobes. Furthermore, growth of L. crispatus (MV-1A-US) is inhibited by Cu2+ ions below biologically relevant concentrations, in vitro. Our work illustrates deleterious effects on the vaginal environment induced by Cu-IUD initiation, which may adversely impact sexual and reproductive health.

Date: 2023
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DOI: 10.1038/s41467-023-36002-4

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