Hormone associated changes to the female genital microbiota in South African adolescents 1Christina Balle, 1Katie Lennard, 1Iyaloo Konstantinus, 1Shameem Jaumdally, 1Rachel Esra, 1Katherine Gill, 3Ulas Karaoz, 3Eoin Brodie, 1Landon Myer, 1Linda-Gail Bekker, 1,3Jo-Ann S Passmore, 1,2,4Heather Jaspan. 1University of Cape Town, South Africa; 2Seattle Children's Research Institute, WA, USA; 3University of California, Berkeley, CA, USA; 4National Health Laboratory Service, South Africa; 5University of Washington, WA, USA Progestin-only injectable contraceptives and the luteal phase of the menstrual cycle have been associated with increased risk of HIV. Hormonal contraception (HC) and endogenous sex hormones may impact HIV risk by altering the female genital tract (FGT) microbiota. We examined the relationship between three HC options, endogenous hormone levels and the adolescent FGT microbiota in a randomized, crossover trial. 131 girls aged 15 to 19 from Cape Town were enrolled and randomized into three study arms: 1. injectable norethisterone enanthate (Net-En), 2. combined oral contraceptives (COCs) or 3. combined contraceptive vaginal ring (CCVR) for 16 weeks followed by 4 months on another HC method. Vaginal swabs were collected at screening, crossover and exit visits for bacterial vaginosis (BV) testing and 16S rRNA gene amplicon sequencing. Blood samples were collected for measurement of estrogen (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Three major FGT community types were identified. Two were dominated by Lactobacillus species (L. crispatus and L. iners, respectively) and the third, most prevalent community, was comprised of mixed anaerobic bacteria. In an intention to treat analysis, the FGT microbiota of participants using COCs was less diverse than the microbiota of Net-En and CCVR users (median Shannon Index = 0.75 vs 1.49 and 1.58, respectively; adj. p<0.05). E2 and LH levels were positively correlated with alpha diveristy and were significantly higher in BV positive compared to BV negative participants. LH and FSH levels were significantly reduced in CCVR and COC users compared to participants not using HC (at baseline) or on Net-En while E2 levels were lower in Net-En and CCVR users compared to no HC use. HC use was associated with alterations in FGT microbiota not likely due to changes in endogenous hormones. Participants on COCs had lower FGT microbial diversity correlating with potentially lower HIV risk.
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