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Investigating the effects of contraceptive use on inflammation in the female genital tract
Hormonal contraceptives are used worldwide by women of reproductive age (15-49 years). Immune cells, cytokines and antimicrobial peptides play an important role in the protection of the female genital tract (FGT) against infections, including HIV and other sexually transmitted infections (STIs). Con...
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| Format: | Thesis |
| Language: | English English |
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Department of Pathology
2026
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| Summary: | Hormonal contraceptives are used worldwide by women of reproductive age (15-49 years). Immune cells, cytokines and antimicrobial peptides play an important role in the protection of the female genital tract (FGT) against infections, including HIV and other sexually transmitted infections (STIs). Contraceptives are thought to cause biological changes in the FGT, possibly altering susceptibility to infection. This project aimed to investigate the biological changes caused by contraceptive use that may impact risk of HIV and STI acquisition. Clinical samples were collected from two hundred and thirty-two participants in three clinical trials: (1) Evidence for Contraceptive Options and HIV Outcomes (ECHO; South Africa); (2) Extended Duration of Sayana Press (Brazil); and (3) Lower Dose medroxyprogesterone acetate (MPA) Pharmacokinetic/Pharmacodynamic (Brazil and Dominican Republic) studies. STIs were assessed by multiplex polymerase chain reaction and reverse hybridisation, cervical CD4+ T cell frequencies by flow cytometry, vaginal cytokines by Luminex and antimicrobial peptides by enzyme-linked immunosorbent assay. In women randomized to levonorgestrel (LNG) implant, copper intrauterine device (copper-IUD) or depot medroxyprogesterone acetate (DMPA-IM; 150mg) in the ECHO trial, even though STI incidence was exceptionally high (107.9/100 wy), there were no significant differences in incidence between arms over three months following contraceptive initiation. Women randomized to DMPA-IM had a greater proportion of cervical 7+CD4+ T cells compared to copper-IUD. Those using LNG implant had an increased proportion of cervical β7+CD4+ T cells following contraceptive initiation and an increased proportion of Th17 cells compared to the copper IUD group. Copper IUD users had significantly higher concentrations of FGT human beta defensin (HBD)-1 and 2 compared to LNG implant and DMPA-IM users post contraceptive initiation. In the Lower Dose study, FGT interleukin (IL)-8 and HBD-1 concentrations were significantly lower three months post contraceptive initiation among women receiving 104mg or 105mg MPA compared to the pre-contraceptive follicular, but not luteal phase. No significant changes in immune mediators were observed in the Sayana Press study over a follow-up period of 12 months. The findings of this study contribute to growing knowledge of the effects of contraceptives on FGT immune factors that may influence susceptibility in infection. |
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