Genital inflammatory status and the innate immune response to contraceptive initiation.

PROBLEM: Data on the effects of contraceptives on female genital tract (FGT) immune mediators are inconsistent, possibly in part due to pre-existing conditions that influence immune mediator changes in response to contraceptive initiation. METHODS: This study included 161 South African women randomised to injectable depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD), or levonorgestrel (LNG) implant in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. We measured thirteen cytokines and antimicrobial peptides previously associated with HIV acquisition in vaginal swabs using Luminex and ELISA, before, and at 1 and 3 months after contraceptive initiation. Women were grouped according to an overall baseline inflammatory profile. We evaluated modification of the relationships between contraceptives and immune mediators by baseline inflammation, demographic, and clinical factors. RESULTS: Overall, LNG implant and copper IUD initiation were associated with increases in inflammatory cytokines, while no changes were observed following DMPA-IM initiation. However, when stratifying by baseline inflammatory profile, women with low baseline inflammation in all groups experienced significant increases in inflammatory cytokines, while those with a high baseline inflammatory profile experienced no change or decreases in inflammatory cytokines. CONCLUSION: We conclude that pre-contraceptive initiation immune profile modifies the effect of contraceptives on the FGT innate immune response.

Effects of three contraceptive methods on depression and sexual function: An ancillary study of the ECHO randomized trial.

OBJECTIVE: To compare the effects of depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant, and copper intrauterine device (IUD) on mood and sexual function. METHODS: At the Effective Care Research Unit in South Africa, women already randomized in the ECHO Trial to the three methods were asked to participate in this study. Participants were interviewed at 3 and 12 months after enrollment using the Beck Depression Inventory and Arizona Sexual Experiences Scale, and at 12 months using the WHO-5 Wellbeing Index and the Patient Global Impression scale. RESULTS: A total of 605 women participated. There was little difference in depression at 3 months across the three study groups. Contrary to our hypothesis, at 12 months, depression was lowest among DMPA-IM users (16/167, 9.6%) and highest among IUD users (28/158, 17.7%) (p = 0.032). There was little difference in sexual function at any time-point. More women in the DMPA-IM group felt "very much better" on the PGI scale than in the IUD and LNG implant groups (p = 0.003). CONCLUSION: Depression may be less likely with DMPA-IM than with the other methods 1 year after initiation. Major differences in sexual functioning are unlikely. Unhappiness related to not using DMPA-IM, the most popular method in our setting, may have skewed results. TRIAL REGISTRATION NUMBER: PACTR201706001651380.

Psychological, behavioural and physiological effects of three long-acting reversible contraception (LARC) methods: protocol for an ancillary study of the ECHO randomised trial.

INTRODUCTION: This is the protocol for an ancillary study to the multicentre Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial, a three-arm randomised trial comparing the effects of depot medroxyprogesterone acetate (DMPA), the levonorgestrel (LNG) implant and the copper intrauterine device (IUD) on HIV incidence (NCT02550067 pre-results). The ancillary study will compare other non-contraceptive effects of these three long-acting, reversible contraceptions about which there is little existing comparative evidence. METHODS AND ANALYSIS: Women randomised to IUD, DMPA and LNG implant (1:1:1) at one of the ECHO trial sites will be asked to participate in the ancillary study at the 1-month follow-up visit. Research staff will interview women that consent to participate at the 3-month follow-up visit. Primary outcomes are depression, sexual dysfunction and menstrual disturbances. The Beck Depression Inventory will be used to assess depression and the Arizona Sexual Experiences Scale to assess sexual dysfunction. Participants will also be asked to prospectively complete a 28-day symptom diary. The required sample size is 522 participants. Depression scores will be analysed as continuous and categorical variables. Analysis will be by intention to treat. ETHICS AND DISSEMINATION: The ancillary study protocol received ethical approval from the University of the Witwatersrand Committee for Research on Human Subjects on 17 February 2016 (reference no. 14112). The results will be disseminated in a peer-reviewed open-access journal. TRIAL REGISTRATION NUMBER: PACTR201706001651380.