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
South Africa
C Avenant, A.J. Bick, S.B. Skosana, S Dlamini, Y Balakrishna, JM Moliki, M Singata-Madliki, G.J. Hofmeyr, J Smit, M Beksinska, I Beesham, I Seocharan, J Batting, P Chen, K Storbeck, D Africander, J.P. Hapgood
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December 06, 2023
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December 06, 2023
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Misreportingcontraceptiveuse
Title
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
Country
| Name | Country code |
|---|---|
| South Africa | ZAR |
Abstract
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 MPA (n=161) and 13.6 (IQR 9.01; 19.0) nM for 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.
The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).
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 MPA (n=161) and 13.6 (IQR 9.01; 19.0) nM for 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.
The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).
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Primary investigators
| Name | Affiliation |
|---|---|
| C Avenant | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |
| A.J. Bick | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |
| S.B. Skosana | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |
| S Dlamini | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |
| Y Balakrishna | Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa |
| JM Moliki | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |
| M Singata-Madliki | Effective Care Research Unit, Eastern Cape Department of Health / Universities of the Witwatersrand and Fort Hare, East London, South Africa |
| G.J. Hofmeyr | Effective Care Research Unit, Eastern Cape Department of Health / Universities of the Witwatersrand and Fort Hare, East London, South Africa |
| J Smit | Wits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa |
| M Beksinska | Wits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa |
| I Beesham | Wits MRU (MatCH Research Unit), Department of Obstetrics and Gynecology, Faculty of Health Sciences, University of the Witwatersrand, Durban, South Africa |
| I Seocharan | Biostatistics Research Unit, South African Medical Research Council, Durban, South Africa |
| J Batting | Effective Care Research Unit, Eastern Cape Department of Health / Universities of the Witwatersrand and Fort Hare, East London, South Africa |
| P Chen | Family Health International (FHI) 360, Durham, North Carolina, USA |
| K Storbeck | Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa |
| D Africander | Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa |
| J.P. Hapgood | Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa |