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More recently, it has become increasingly clear that sex hormones regulate susceptibility to sexually transmitted infections through direct and indirect mechanisms involving inflammation and immune responses. The reproductive cycle can influence simian\/human immunodeficiency virus (SHIV) infections in primates and HIV-1 infection in ex vivo cervical tissues from women. Exogenous hormones, such as those found in hormonal contraceptives, have come under intense scrutiny because of the increased susceptibility to sexually transmitted infections seen in women using medroxyprogesterone acetate, a synthetic progestin-based contraceptive. Recent meta-analyses concluded that medroxyprogesterone acetate enhanced HIV-1 susceptibility in women by 40%. In contrast, estradiol-containing hormonal contraceptives were not associated with increased susceptibility and some studies reported a protective effect of estrogen on HIV\/SIV infection, although the underlying mechanisms remain incompletely understood. Recent studies describe a key role for the vaginal microbiota in determining susceptibility to sexually transmitted infections, including HIV-1. While Lactobacillus spp.-dominated vaginal microbiota is associated with decreased susceptibility, complex microbiota, such as those seen in bacterial vaginosis, correlates with increased susceptibility to HIV-1. Interestingly, sex hormones are inherently linked to microbiota regulation in the vaginal tract. Estrogen has been postulated to play a key role in establishing a Lactobacillus-dominated microenvironment, whereas medroxyprogesterone acetate is linked to hypo-estrogenic effects. The aim of this Review is to contribute to a better understanding of the sex-hormone\u2013microbiome\u2013immunity axis, which can provide key information on the determinants of HIV-1 susceptibility in the female genital tract and, consequently, inform HIV-1 prevention strategies.<\/jats:p>","DOI":"10.1242\/dmm.035147","type":"journal-article","created":{"date-parts":[[2018,8,28]],"date-time":"2018-08-28T04:48:26Z","timestamp":1535431706000},"source":"Crossref","is-referenced-by-count":93,"title":["The relationship between sex hormones, the vaginal microbiome and immunity in HIV-1 susceptibility in women"],"prefix":"10.1242","volume":"11","author":[{"given":"Jocelyn M.","family":"Wessels","sequence":"first","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, Michael G. DeGroote Centre for Learning and Discovery, McMaster University 1 , Hamilton, Ontario L8S 4L8 , Canada"},{"name":"McMaster University 2 Department of Pathology and Molecular Medicine , , Hamilton, Ontario L8S 4L8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Felker","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, Michael G. DeGroote Centre for Learning and Discovery, McMaster University 1 , Hamilton, Ontario L8S 4L8 , Canada"},{"name":"McMaster University 2 Department of Pathology and Molecular Medicine , , Hamilton, Ontario L8S 4L8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley A.","family":"Dupont","sequence":"additional","affiliation":[{"name":"McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, Michael G. 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