Conclusions
overweight
OBESE
Peak serum levels of MPA and NET are lower and less variable than expected from the literature, suggesting that side-effect profiles for both may be lower than predicted based only on progestin concentrations, and less variable between women. Most participants in the WHICH trial were overweight or obese, which we show for the first time significantly and negatively associates with the peak serum progestin levels for both DMPA-IM and NET-EN users. Based on affinities for the GR, MPA peak serum concentrations may exert side-effects via the GR in select tissues and on select genes, unlike NET. Our results suggest that when comparing effects of DMPA-IM in clinical trials in sub-Saharan Africa with those of other contraceptives that are much less widely used, analysis of health outcomes and biological responses are more likely to be confounded by the presence of MPA in the other contraceptive arms than the reciprocal effect. In such trials, effects of DMPA-IM relative to baseline are also likely underestimated in the DMPA-IM arm at sites where DMPA-IM is widely used. Biological and health outcomes may also be confounded by non-study progestins other than MPA, such as NET and LNG. This is likely due to high levels of misreporting of contraceptive use before and during trials. Furthermore, our study highlights the potential problem of progestin ‘tails’ for MPA and NET and suggests that not using DMPA-IM or NET-EN less than six or four months, respectively, prior to initiation is insufficient time to control for this potential problem. In addition, reported side-effect and health outcome profiles are likely to differ between trials where median BMIs and weights of participants are significantly different.