{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:34:39Z","timestamp":1793198079366,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":222,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n Alfonso Martin Escudero","id":[{"id":"https:\/\/ror.org\/02897ye82","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Medical Research Council and National Institute for Health Research","award":["MC_PC_12025"],"award-info":[{"award-number":["MC_PC_12025"]}],"id":[{"id":"https:\/\/ror.org\/0187kwz08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute for Health Research (NIHR) Imperial Biomedical Research Centre","id":[{"id":"https:\/\/ror.org\/01kmhx639","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Placental production of steroids, like progesterone, drives increasing circulating concentrations during pregnancy. It is postulated that reduced cervicovaginal progesterone contributes to cervical shortening and increased preterm birth (PTB) risk. Although vaginal progesterone is recommended for PTB prevention, its effectiveness remains uncertain. While serum and urinary progesterone are routinely measured in pregnancy, little is known about cervicovaginal fluid (CVF) progesterone concentrations. To address this, we adapted existing mass spectrometry-based assays to quantify 13 steroid hormones in CVF collected between 12 and 24\u2009weeks gestation from uncomplicated term pregnancies (n\u2009=\u200914) and those with adverse outcomes (n\u2009=\u200911). Only progesterone, androstenedione, and cortisol were detected above detection limits. In uncomplicated term pregnancies, mean concentrations of these steroids were 6.61\u2009\u00b1\u20098.13, 4.16\u2009\u00b1\u20092.98, and 0.34\u2009\u00b1\u20090.21\u2009ng\/g of CVF, respectively. Cervicovaginal progesterone was weakly, positively associated with gestational age (r2= 0.15, P-value= 0.02) which was also observed in paired samples collected at 12 and 22\u2009weeks (n\u2009=\u20095, paired Wilcoxon, P-value = 0.03). No differences in CVF steroid levels were observed between women who subsequently delivered preterm (n\u2009=\u20099) or at term (n\u2009=\u200915). Our study provides a robust method for quantifying CVF steroids and suggests that second-trimester PTB risk is not associated with cervicovaginal progesterone concentrations.<\/jats:p>","DOI":"10.1093\/molehr\/gaag045","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:20:37Z","timestamp":1786360837000},"source":"Crossref","is-referenced-by-count":0,"title":["Mass spectrometry-based quantitation of cervicovaginal progesterone and steroids in women at high risk of preterm birth"],"prefix":"10.1093","volume":"32","author":[{"given":"Katia","family":"Capuccini","sequence":"first","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gon\u00e7alo D S","family":"Correia","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Olmo Garcia","sequence":"additional","affiliation":[{"name":"The National Phenome Centre, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Uhlson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Colorado Anschutz Medical Campus , Aurora, CO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada H Y","family":"Yuen","sequence":"additional","affiliation":[{"name":"The National Phenome Centre, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belen","family":"Gimeno-Molina","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Sykes","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]},{"name":"The Parasol Foundation Centre for Women\u2019s Health and Cancer Research, Imperial College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Takats","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"The National Phenome Centre, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Colorado Anschutz Medical Campus , Aurora, CO,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R","family":"Lewis","sequence":"additional","affiliation":[{"name":"The National Phenome Centre, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College, London, UK"},{"name":"Life Sciences Mass Spectrometry Division, Bruker UK Limited, Coventry, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip R","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-5567","authenticated-orcid":false,"given":"David A","family":"Macintyre","sequence":"additional","affiliation":[{"name":"Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London , London,","place":["UK"]},{"name":"March of Dimes Prematurity Research Centre at Imperial College London , London,","place":["UK"]},{"name":"Robinson Research Institute, Adelaide University , Adelaide, SA,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"2026102810194076000_gaag045-B1","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1016\/S2214-109X(18)30451-0","article-title":"Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis","volume":"7","author":"Chawanpaiboon","year":"2019","journal-title":"Lancet Global Health"},{"key":"2026102810194076000_gaag045-B2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/humrep\/15.suppl_1.159","article-title":"Mechanisms of uterine specificity of vaginal progesterone","volume":"15(Suppl 1)","author":"Cicinelli","year":"2000","journal-title":"Hum Reprod"},{"key":"2026102810194076000_gaag045-B3","doi-asserted-by":"crossref","first-page":"e1002390","DOI":"10.1371\/journal.pmed.1002390","article-title":"Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): a multicentre, randomised, placebo-controlled trial","volume":"14","author":"Crowther","year":"2017","journal-title":"PLoS Med"},{"key":"2026102810194076000_gaag045-B4","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/ijgo.12564","article-title":"The association between serum progesterone level and preterm delivery","volume":"142","author":"Feng","year":"2018","journal-title":"Int J Gynaecol Obstet"},{"key":"2026102810194076000_gaag045-B5","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1080\/09513590410001692519","article-title":"High local endometrial effect of vaginal progesterone gel","volume":"18","author":"Ficicioglu","year":"2004","journal-title":"Gynecol Endocrinol"},{"key":"2026102810194076000_gaag045-B6","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1021\/pr070529w","article-title":"Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future","volume":"6","author":"Good","year":"2007","journal-title":"J Proteome Res"},{"key":"2026102810194076000_gaag045-B7","doi-asserted-by":"crossref","first-page":"6326","DOI":"10.1002\/pmic.200600284","article-title":"Human body fluid proteome analysis","volume":"6","author":"Hu","year":"2006","journal-title":"Proteomics"},{"key":"2026102810194076000_gaag045-B8","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jogc.2019.04.012","article-title":"Guideline No. 398: progesterone for prevention of spontaneous preterm birth","volume":"42","author":"Jain","year":"2020","journal-title":"J Obstet Gynaecol Can"},{"key":"2026102810194076000_gaag045-B9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40168-016-0223-9","article-title":"The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk","volume":"5","author":"Kindinger","year":"2017","journal-title":"Microbiome"},{"key":"2026102810194076000_gaag045-B10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1472-6890-14-33","article-title":"Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction","volume":"14","author":"Krasowski","year":"2014","journal-title":"BMC Clin Pathol"},{"key":"2026102810194076000_gaag045-B11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/s12884-018-2002-z","article-title":"Serum progesterone distribution in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective cohort study","volume":"18","author":"Ku","year":"2018","journal-title":"BMC Pregnancy Childbirth"},{"key":"2026102810194076000_gaag045-B12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.12688\/f1000research.17525.2","article-title":"Correlation of cervical progesterone levels to plasma progesterone levels in normal pregnancy and preterm labor: a cross-sectional study","volume":"8","author":"Lisnawati","year":"2022","journal-title":"F1000Res"},{"key":"2026102810194076000_gaag045-B13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/humupd\/dmu008","article-title":"Androgens in pregnancy: roles in parturition","volume":"20","author":"Makieva","year":"2014","journal-title":"Hum Reprod Update"},{"key":"2026102810194076000_gaag045-B14","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1016\/j.cell.2024.05.005","article-title":"Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas","volume":"187","author":"McCurry","year":"2024","journal-title":"Cell"},{"key":"2026102810194076000_gaag045-B15","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/physrev.00058.2017","article-title":"The UDP-glycosyltransferase (UGT) superfamily: new members, new functions, and novel paradigms","volume":"99","author":"Meech","year":"2019","journal-title":"Physiol Rev"},{"key":"2026102810194076000_gaag045-B16","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1056\/NEJMoa035140","article-title":"Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate","volume":"348","author":"Meis","year":"2003","journal-title":"N Engl J Med"},{"key":"2026102810194076000_gaag045-B17","first-page":"191","article-title":"Steroid sulfatase activity in human leukocytes","volume":"38","author":"Miyakawa","year":"1994","journal-title":"Gynecol Obstet Invest"},{"key":"2026102810194076000_gaag045-B18","doi-asserted-by":"crossref","first-page":"11565","DOI":"10.1038\/ncomms11565","article-title":"Molecular evidence of functional progesterone withdrawal in human myometrium","volume":"7","author":"Nadeem","year":"2016","journal-title":"Nat Commun"},{"key":"2026102810194076000_gaag045-B19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/1933719110395404","article-title":"Effect of prolonged in vivo administration of progesterone in pregnancy on myometrial gene expression, peripheral blood leukocyte activation, and circulating steroid hormone levels","volume":"18","author":"Norman","year":"2011","journal-title":"Reprod Sci"},{"key":"2026102810194076000_gaag045-B20","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1038\/s41467-021-26215-w","article-title":"Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth","volume":"12","author":"Pruski","year":"2021","journal-title":"Nat Commun"},{"key":"2026102810194076000_gaag045-B21","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/ijgo.15514","article-title":"Prediction and prevention of preterm birth: quality assessment and systematic review of clinical practice guidelines using the AGREE II framework","volume":"166","author":"Ramachandran","year":"2024","journal-title":"Int J Gynaecol Obstet"},{"key":"2026102810194076000_gaag045-B22","doi-asserted-by":"crossref","first-page":"e58343","DOI":"10.7554\/eLife.58343","article-title":"Developing a theoretical evolutionary framework to solve the mystery of parturition initiation","volume":"9","author":"Rokas","year":"2020","journal-title":"eLife"},{"key":"2026102810194076000_gaag045-B23","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2217\/WHE.11.60","article-title":"Vaginal progesterone to reduce the rate of preterm birth and neonatal morbidity: a solution at last","volume":"7","author":"Romero","year":"2011","journal-title":"Womens Health (Lond)"},{"key":"2026102810194076000_gaag045-B24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.steroids.2007.05.003","article-title":"Superiority of gas chromatography\/tandem mass spectrometry assay (GC\/MS\/MS) for estradiol for monitoring of aromatase inhibitor therapy","volume":"72","author":"Santen","year":"2007","journal-title":"Steroids"},{"key":"2026102810194076000_gaag045-B25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.jsbmb.2010.05.001","article-title":"Advantages and challenges of mass spectrometry assays for steroid hormones","volume":"121","author":"Stanczyk","year":"2010","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026102810194076000_gaag045-B26","doi-asserted-by":"crossref","first-page":"5944","DOI":"10.1210\/jcem.86.12.8081","article-title":"Differential expression of sulfotransferase enzymes involved in thyroid hormone metabolism during human placental development","volume":"86","author":"Stanley","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2026102810194076000_gaag045-B27","doi-asserted-by":"crossref","first-page":"105999","DOI":"10.1016\/j.psyneuen.2022.105999","article-title":"Maternal serum cortisol levels during pregnancy differ by fetal sex","volume":"149","author":"Vrijkotte","year":"2023","journal-title":"Psychoneuroendocrinology"},{"key":"2026102810194076000_gaag045-B28","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1039\/D4OB00327F","article-title":"Recent developments in the enzymatic modifications of steroid scaffolds","volume":"22","author":"Wang","year":"2024","journal-title":"Org Biomol Chem"},{"key":"2026102810194076000_gaag045-B29","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.1073\/pnas.1200650109","article-title":"MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor","volume":"109","author":"Williams","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026102810194076000_gaag045-B30","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1021\/ac070494j","article-title":"Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry","volume":"79","author":"Xu","year":"2007","journal-title":"Anal Chem"}],"container-title":["Molecular Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/molehr\/advance-article-pdf\/doi\/10.1093\/molehr\/gaag045\/70609376\/gaag045.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/32\/4\/gaag045\/70609376\/gaag045.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/molehr\/article-pdf\/32\/4\/gaag045\/70609376\/gaag045.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:19:50Z","timestamp":1793197190000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/molehr\/article\/doi\/10.1093\/molehr\/gaag045\/8758878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10,6]]}},"URL":"https:\/\/doi.org\/10.1093\/molehr\/gaag045","relation":{},"ISSN":["1360-9947","1460-2407"],"issn-type":[{"value":"1360-9947","type":"print"},{"value":"1460-2407","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"gaag045"}}