Medroxyprogesterone acetate (MPA) is the active molecule in Depo-Proveraw (DMPA), an injectable, long-acting reversible contraceptive (LARC). Because DMPA is a commonly used LARC in countries with higher prevalences of HIV-1 and other sexually transmitted infections, epidemiological studies indicating that DMPA enhances susceptibility of women to acquisition of these diseases are especially disconcerting. For example, Heffron and colleagues published findings from observational studies in seven African countries showing that women using injectable LARC, including DMPA, were twice as likely to acquire HIV than women not using hormonal contraception (HC)(Heffron et al., 2012). Objections however were quickly raised regarding the reliability of this data, including its low biological plausibility and the high likelihood that results had been confounded by unmeasured differences in condom usage and frequency of unprotected intercourse between the HC users and non-users (Gray, 2012; Hubacher, 2012; Shelton, 2012; van Leeuewn and de Vries, 2012). Moreover, discordant results between other studies exploring links between DMPA and HIV acquisition implied that uncontrolled differences among HC users and non-users were similarly responsible for systematic study biases (Baeten et al., 2007; Kleinschmidt et al., 2007; Morrison et al., 2007, 2010, 2014;