New approaches for developing biomarkers of hormonal contraceptive use

Abstract To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokin...

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Main Authors: Rakhee Sachdeva, Narender Kumar, Vivian Brache, Barbara A. Friedland, Marlena Plagianos, Shimin Zhang, Larisa Kizima, Leila Cochon, Ana Sofía Tejada Tabar, Ann Blanc, Ruth B. Merkatz
Format: Article
Language:English
Published: Nature Portfolio 2023-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-24215-4
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author Rakhee Sachdeva
Narender Kumar
Vivian Brache
Barbara A. Friedland
Marlena Plagianos
Shimin Zhang
Larisa Kizima
Leila Cochon
Ana Sofía Tejada Tabar
Ann Blanc
Ruth B. Merkatz
author_facet Rakhee Sachdeva
Narender Kumar
Vivian Brache
Barbara A. Friedland
Marlena Plagianos
Shimin Zhang
Larisa Kizima
Leila Cochon
Ana Sofía Tejada Tabar
Ann Blanc
Ruth B. Merkatz
author_sort Rakhee Sachdeva
collection DOAJ
description Abstract To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users’ saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.
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spelling doaj.art-9ce99506d9404150bf8f4b210102e8fc2023-01-08T12:10:04ZengNature PortfolioScientific Reports2045-23222023-01-0113111110.1038/s41598-022-24215-4New approaches for developing biomarkers of hormonal contraceptive useRakhee Sachdeva0Narender Kumar1Vivian Brache2Barbara A. Friedland3Marlena Plagianos4Shimin Zhang5Larisa Kizima6Leila Cochon7Ana Sofía Tejada Tabar8Ann BlancRuth B. Merkatz9Center for Biomedical Research, Population CouncilCenter for Biomedical Research, Population CouncilClinica de ProfamiliaCenter for Biomedical Research, Population CouncilCenter for Biomedical Research, Population CouncilCenter for Biomedical Research, Population CouncilCenter for Biomedical Research, Population CouncilClinica de ProfamiliaClinica de ProfamiliaCenter for Biomedical Research, Population CouncilAbstract To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC–MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users’ saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.https://doi.org/10.1038/s41598-022-24215-4
spellingShingle Rakhee Sachdeva
Narender Kumar
Vivian Brache
Barbara A. Friedland
Marlena Plagianos
Shimin Zhang
Larisa Kizima
Leila Cochon
Ana Sofía Tejada Tabar
Ann Blanc
Ruth B. Merkatz
New approaches for developing biomarkers of hormonal contraceptive use
Scientific Reports
title New approaches for developing biomarkers of hormonal contraceptive use
title_full New approaches for developing biomarkers of hormonal contraceptive use
title_fullStr New approaches for developing biomarkers of hormonal contraceptive use
title_full_unstemmed New approaches for developing biomarkers of hormonal contraceptive use
title_short New approaches for developing biomarkers of hormonal contraceptive use
title_sort new approaches for developing biomarkers of hormonal contraceptive use
url https://doi.org/10.1038/s41598-022-24215-4
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