Abstract
BackgroundCervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives.MethodsWe collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis.ResultsCytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota.ConclusionsBoth DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.
Highlights
Women represent more than half of the 37 million people currently living with HIV [1]
Age-related, prevalence of active C. trachomatis and N. gonorrhoeae infections tended to be higher in women initiating norethisterone enanthate (NET-EN) (14/44; 31.8%) compared those initiating DMPA-IM (9/53; 17.0%; p=0.141), as did Nugent-bacterial vaginosis (BV) prevalence (40.9% vs. 25.0%; p=0.085), while sexual risk behaviour was comparable between groups (Table 1)
Based on the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial results [9], the WHO concluded that women, including those at high risk of HIV acquisition, could safely use any form of reversible contraception evaluated in the Trial, including progestogen-only injectables, the trial did not evaluate the effect of the progestogenonly injectable NET-EN on HIV risk
Summary
Women represent more than half of the 37 million people currently living with HIV [1]. Prior to the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial [9], observational studies suggested that the use of injectable progestogen contraceptives might increase HIV risk [10, 11]. Such contraceptives, intramuscular depomedroxyprogesterone acetate (DMPA-IM) and intramuscular norethisterone enanthate (NET-EN), are the most commonly used contraceptives in SSA because they are convenient, longacting, and reversible [12, 13]. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives
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