Introduction
SEXUALLY TRANSMITTED INFECTIONS
Injectable progestin-only contraceptives are the most used contraceptive methods in sub-Saharan Africa [Previous studies have reported large inter-individual and inter-study variations in serum MPA and NET levels, with differences in reported peak serum levels of 38- to 48-fold between studies (reviewed in [Determining the concentrations of serum progestins is important for several reasons. Progestins may elicit dose-dependent biological side-effects such as increased risk of HIV and other sexually transmitted infections, decreased bone density and weight change [Differential side-effects between MPA and NET are likely mediated by their different affinities for and activities via members of the steroid receptor family [It is becoming clear that objective quantification of serum progestin levels is necessary to validate unreliable self-reporting of contraceptive use within and prior to the trial enrolment [We therefore sought to quantify MPA and NET concentrations in a highly powered randomized trial without several of the abovementioned confounding factors. We report here for the first time, the baseline and peak serum concentrations of MPA and NET in a large cohort of 435 South African women randomized equally to either DMPA-IM or NET-EN, from the Women’s Health, Injectable Contraceptive and HIV (WHICH) clinical trial. Samples were taken at study enrolment, prior to the first injection (baseline, D0) and one-week after the 24 weeks (24W) contraceptive injection, i.e. after three doses of DMPA-IM and four doses of NET-EN (at 25 weeks or 25W). We performed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) to investigate the concentrations of MPA and NET as well as other potentially confounding progestins that are commonly used in alternative contraceptive methods in South Africa [