Circulating concentrations of progestins used in contraception

Bick, Alexis J; Louw, Renate; Skosana, Salndave B.; Africander, Donita; Hapgood, Janet P.

doi:10.17632/5sck77c9b9.1

Cited by 1 publication

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“…any quantifiable non-study progestins at 25W. Many different studies have previously investigated peak serum concentrations for MPA in DMPA-IM users, some having measured at multiple time points, and using different methods including radioimmunoassay and LC-MS/MS (reviewed in [5][6][7]). Our data fall within the lower range of peak serum values (2.6 nM to 30 nM) reported for most of the published studies but are much lower than the range of 60 nM to 100 nM reported in some other studies (reviewed in [5][6][7]).…”

Section: Plos Onementioning

confidence: 99%

“…Many different studies have previously investigated peak serum concentrations for MPA in DMPA-IM users, some having measured at multiple time points, and using different methods including radioimmunoassay and LC-MS/MS (reviewed in [5][6][7]). Our data fall within the lower range of peak serum values (2.6 nM to 30 nM) reported for most of the published studies but are much lower than the range of 60 nM to 100 nM reported in some other studies (reviewed in [5][6][7]). We report a median peak serum concentration for NET at 25W of 13.6 nM (4.06 ng/mL) (IQR 9.01-19.0 nM) for the whole cohort of 220 women and 13.3 nM (3.97 ng/mL) (IQR 9.28-18.5 nM) for a subgroup of 155 women (PP1 analysis).…”

Section: Plos Onementioning

confidence: 99%

“…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 [5]). MPA in serum of DMPA-IM users reportedly reaches a peak of 2.6-100 nM within the first few weeks post-injection, while peak NET levels reach 2.4-117 nM (reviewed in [5][6][7]). However, many of the published studies of peak concentrations had small sample sizes and used quantification methods such as radioimmunoassay without prior extraction (reviewed in [7]).…”

Section: Introductionmentioning

confidence: 99%

“…More recent clinical studies, although using high-throughput and highly sensitive liquid chromatography-mass spectrometry (LC-MS) methods, may be confounded by: unequal numbers of participants using DMPA-IM and NET-EN, comparing samples from non-randomized trials or inter-study comparisons, differences in intrinsic participant demographic characteristics, using sampling time frames that do not correlate with peak levels, and using different progestin quantification methods [5,7]. Our detailed review of available data suggests that peak serum levels of MPA and NET are reached at about one week post-injection [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Misreporting contraceptive use and the association of peak study progestin levels with weight and BMI among women randomized to the progestin-only injectable contraceptives DMPA-IM and NET-EN

Avenant,

Bick,

Skosana

et al. 2023

PLoS ONE

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Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan Africa. Insufficient robust data on their relative side-effects and serum concentrations limit understanding of reported outcomes in contraception trials. The WHICH clinical trial randomized HIV-negative women to DMPA-IM (n = 262) or norethisterone enanthate (NET-EN) (n = 259) at two South African sites between 2018–2019. We measured serum concentrations of study and non-study progestins at initiation (D0) and peak serum levels, one week after the 24-week injection [25 weeks (25W)], (n = 435) and investigated associations between study progestin levels, and BMI and weight of participants. Peak median serum concentrations were 6.59 (IQR 4.80; 8.70) nM for medroxyprogesterone (MPA) (n = 161) and 13.6 (IQR 9.01; 19.0) nM for norethisterone (NET) (n = 155). MPA was the most commonly quantifiable non-study progestin at D0 in both arms (54%) and at 25W in the NET-EN arm (27%), followed by NET at D0 in both arms (29%) and at 25W in the DMPA-IM arm (19%). Levonorgestrel was quantifiable in both arms [D0 (6.9%); 25W (3.4%)], while other progestins were quantifiable in ≤ 14 participants. Significant negative time-varying associations were detected between MPA and NET concentrations and weight and BMI in both contraceptive arms and a significant increase was detected for peak serum progestin concentrations for normal weight versus obese women. Contraceptive-related reported outcomes are likely confounded by MPA, more so than NET, with reported DMPA-IM effects likely underestimated, at sites where DMPA-IM is widely used, due to misreporting of contraceptive use before and during trials, and ‘tail’ effects of DMPA-IM use more than six months before trial enrolment. Peak serum levels of MPA and NET are negatively associated with BMI and weight, suggesting another source of variability between trial outcomes and a potential increase in side-effects for normal weight versus overweight and obese women. Trail registration: The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).

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