Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020
Impact of Hormonal Contraceptives on Cervical T-helper 17 Phenotype and Function in Adolescents: Results from a Randomized, Crossover Study Comparing Long-acting Injectable Norethisterone Oenanthate (NET-EN), Combined Oral Contraceptive Pills, and Combined Contraceptive Vaginal Rings.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Injectable Contraceptives Differentially Affect Select CD4+ HIV-1 Target Cells in the Genital Tract but Not Systemically: Implications for HIV-1 Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025Trial
- Systems analysis reveals differential expression of endocervical genes in African women randomized to DMPA-IM, LNG implant or cu-IUD.Clinical immunology (Orlando, Fla.) · 2023Trial
- Persistent, Asymptomatic Colonization withMicrobiology spectrum · 2022Trial
- Impact of the menstrual cycle and ethinyl estradiol/etonogestrel contraceptive vaginal ring on granulysin and other mucosal immune mediators.American journal of reproductive immunology (New York, N.Y. : 1989) · 2021Trial
- Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial.Nature communications · 2020Trial
- Experimental models for intestinal host-microbe interactions.EMBO molecular medicine · 2026Review
- Short-term HPV detection dynamics across hormonal contraceptive methods in adolescent girls and young women: a secondary analysis of a randomized trial in South Africa.Research square · 2026Article
- Impact of Hormonal Contraceptives on HPV Dynamics in Adolescent Girls and Young Women: Insights from a Randomized Controlled Sub-Study in South Africa.medRxiv : the preprint server for health sciences · 2025Article
- Pathophysiological Consequences Associated with Hormonal Contraceptives Use in Sub-Saharan Africa: A Scoping Review.Open access journal of contraception · 2025Review
- A Noninvasive Method to Sample Immune Cells in the Lower Female Genital Tract Using Menstrual Discs.ImmunoHorizons · 2024Article
- Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy.Frontiers in immunology · 2024Review
- Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents.Viruses · 2023Article
- Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.Molecular and cellular endocrinology · 2023Article
- Systems Analysis Reveals Contraceptive-Induced Alteration of Cervicovaginal Gene Expression in a Randomized Trial.Frontiers in reproductive health · 2022Article
- Relationship between the Oral and Vaginal Microbiota of South African Adolescents with High Prevalence of Bacterial Vaginosis.Microorganisms · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAdolescents in sub-Saharan Africa are at risk for human immunodeficiency virus (HIV) infection and unintended pregnancies. Observational studies suggest that injectable hormonal contraceptives (HCs) increase the HIV risk, although their effects on genital inflammation, particularly HIV-susceptible T-helper 17 (Th17) cells, are unknown. In a randomized crossover study, the effect of injectable norethisterone oenanthate (NET-EN), combined contraceptive vaginal rings (CCVR; NuvaRing), and combined oral contraceptive pills (COCPs) on cervical Th17 cells and cytokines were compared.
methodsAdolescents (n = 130; 15-19 years) were randomly assigned 1:1:1 to NET-EN, CCVR, or COCPs for 16 weeks, then subsequently crossed over to another HC for 16 weeks. Estrogen, follicular stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured. Chemokine receptor 5 (CCR5), human leukocyte antigen (HLA) DR isotope, and cluster of differentiation 38 (CD38) expression by cervical cytobrush-derived CD4+ T cells was assessed by fluorescence-activated cell sorting. Th17 cells were defined as CCR6+ and CCR10-. Cervicovaginal Th17-related cytokines were measured by Luminex.
resultsCCVR use for the first 16 weeks was associated with reduced Th17 frequencies and lower FSH and LH concentrations, as compared to NET-EN and COCPs, with FSH concentrations and Th17 frequencies correlating significantly. However, Th17-related cytokine concentrations (interleukin [IL]-21, IL-1β, tumor necrosis factor-α, interferon-γ) and CCR5, HLA-DR, CD38, and Th17 frequencies were significantly higher in CCVR than NET-EN and COCP. At crossover, CCVR users changing to COCPs or NET-EN did not resolve activation or cytokines, although switching from COCP to CCVRs increased cytokine concentrations.
conclusionsCCVR use altered endogenous hormone levels and associated cervical Th17 cell frequencies to a greater extent than use of NET-EN or COCPs, although Th17 cells were more activated and Th17-related cytokine concentrations were elevated. While CCVRs may impact the HIV risk by regulating Th17 numbers, increased activation and inflammation may balance any risk gains.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.