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Concentrations of 48 cytokines were measured in the cervicovaginal lavage (CVL) and plasma, and their expression was compared between participants with detectable NET\u2010EN (n\u00a0=\u00a0201) versus non\u2010detectable IHC (n\u00a0=\u00a090). Each log10 cytokine concentration was tested as an outcome in linear\u2010mixed models, with NET\u2010EN detection as the main explanatory variable. Multivariable models were adjusted for potential confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In bivariate analysis, detectable NET\u2010EN was associated with reduced cervicovaginal M\u2010CSF (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.008), GM\u2010CSF (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.025) and G\u2010CSF (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.039), and elevated levels MIF (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.008), IL\u201018 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.011), RANTES (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.005) and IL\u20101R\u03b1 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Lower G\u2010CSF (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.011) and elevated IL\u20101R\u03b1 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.008) remained significant in adjusted models. Multivariable analyses of plasma samples obtained from NET\u2010EN\u2010detectable women showed a significant increase in IP\u201010 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.026) and reductions in TNF\u2010\u03b2 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.037), RANTES (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.009), and M\u2010CSF (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). While similar growth factor reduction in CVL was noted for both DMPA and NET\u2010EN, similar trends were not observed for endogenous progesterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Detectable NET\u2010EN was associated with reduced growth factors in the plasma and genital tract; particularly G\u2010CSF and M\u2010CSF. Our results suggest that while NET\u2010EN is not inflammatory, it may have important immunological effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13411","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T12:47:05Z","timestamp":1614516425000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genital and systemic immune effects of the injectable, contraceptive norethisterone enanthate (NET\u2010EN), in South African women"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-9858","authenticated-orcid":false,"given":"Refilwe P.","family":"Molatlhegi","sequence":"first","affiliation":[{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA) Durban South Africa"},{"name":"Department of Medical Microbiology University of KwaZulu\u2010Natal Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samkelisiwe","family":"Ngcobo","sequence":"additional","affiliation":[{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA) Durban South Africa"},{"name":"Department of Medical Microbiology University of KwaZulu\u2010Natal Durban South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenine J. 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