Quantitative serial MRI of the treated fibroid uterus

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dc.contributor.authorMunro, Kirsty Ien_ZA
dc.contributor.authorThrippleton, Michael Jen_ZA
dc.contributor.authorWilliams, Alistair R Wen_ZA
dc.contributor.authorMcKillop, Grahamen_ZA
dc.contributor.authorWalker, Janeen_ZA
dc.contributor.authorHorne, Andrew Wen_ZA
dc.contributor.authorNewby, David Een_ZA
dc.contributor.authorAnderson, Richard Aen_ZA
dc.contributor.authorSemple, Scott Ien_ZA
dc.contributor.authorMarshall, Ianen_ZA
dc.contributor.authorLewis, Steff Cen_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.contributor.authorBastin, Mark Een_ZA
dc.contributor.authorCritchley, Hilary O Den_ZA
dc.date.accessioned2016-01-11T06:46:26Z
dc.date.available2016-01-11T06:46:26Z
dc.date.issued2014en_ZA
dc.description.abstractObjective There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction. METHODS: Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months). RESULTS: A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061). CONCLUSION: DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids. Trial Registration ClinicalTrials.gov NCT00746031en_ZA
dc.identifier.apacitationMunro, K. I., Thrippleton, M. J., Williams, A. R. W., McKillop, G., Walker, J., Horne, A. W., ... Critchley, H. O. D. (2014). Quantitative serial MRI of the treated fibroid uterus. <i>PLoS One</i>, http://hdl.handle.net/11427/16225en_ZA
dc.identifier.chicagocitationMunro, Kirsty I, Michael J Thrippleton, Alistair R W Williams, Graham McKillop, Jane Walker, Andrew W Horne, David E Newby, et al "Quantitative serial MRI of the treated fibroid uterus." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16225en_ZA
dc.identifier.citationMunro, K. I., Thrippleton, M. J., Williams, A. R., McKillop, G., Walker, J., Horne, A. W., ... & Lewis, S. C. (2014). Quantitative serial MRI of the treated fibroid uterus. PloS one, 9(3), e89809. doi:10.1371/journal.pone.0089809en_ZA
dc.identifier.ris TY - Journal Article AU - Munro, Kirsty I AU - Thrippleton, Michael J AU - Williams, Alistair R W AU - McKillop, Graham AU - Walker, Jane AU - Horne, Andrew W AU - Newby, David E AU - Anderson, Richard A AU - Semple, Scott I AU - Marshall, Ian AU - Lewis, Steff C AU - Millar, Robert P AU - Bastin, Mark E AU - Critchley, Hilary O D AB - Objective There are no long-term medical treatments for uterine fibroids, and non-invasive biomarkers are needed to evaluate novel therapeutic interventions. The aim of this study was to determine whether serial dynamic contrast-enhanced MRI (DCE-MRI) and magnetization transfer MRI (MT-MRI) are able to detect changes that accompany volume reduction in patients administered GnRH analogue drugs, a treatment which is known to reduce fibroid volume and perfusion. Our secondary aim was to determine whether rapid suppression of ovarian activity by combining GnRH agonist and antagonist therapies results in faster volume reduction. METHODS: Forty women were assessed for eligibility at gynaecology clinics in the region, of whom thirty premenopausal women scheduled for hysterectomy due to symptomatic fibroids were randomized to three groups, receiving (1) GnRH agonist (Goserelin), (2) GnRH agonist+GnRH antagonist (Goserelin and Cetrorelix) or (3) no treatment. Patients were monitored by serial structural, DCE-MRI and MT-MRI, as well as by ultrasound and serum oestradiol concentration measurements from enrolment to hysterectomy (approximately 3 months). RESULTS: A volumetric treatment effect assessed by structural MRI occurred by day 14 of treatment (9% median reduction versus 9% increase in untreated women; P = 0.022) and persisted throughout. Reduced fibroid perfusion and permeability assessed by DCE-MRI occurred later and was demonstrable by 2-3 months (43% median reduction versus 20% increase respectively; P = 0.0093). There was no apparent treatment effect by MT-MRI. Effective suppression of oestradiol was associated with early volume reduction at days 14 (P = 0.041) and 28 (P = 0.0061). CONCLUSION: DCE-MRI is sensitive to the vascular changes thought to accompany successful GnRH analogue treatment of uterine fibroids and should be considered for use in future mechanism/efficacy studies of proposed fibroid drug therapies. GnRH antagonist administration does not appear to accelerate volume reduction, though our data do support the role of oestradiol suppression in GnRH analogue treatment of fibroids. Trial Registration ClinicalTrials.gov NCT00746031 DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0089809 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Quantitative serial MRI of the treated fibroid uterus TI - Quantitative serial MRI of the treated fibroid uterus UR - http://hdl.handle.net/11427/16225 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16225
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0089809
dc.identifier.vancouvercitationMunro KI, Thrippleton MJ, Williams ARW, McKillop G, Walker J, Horne AW, et al. Quantitative serial MRI of the treated fibroid uterus. PLoS One. 2014; http://hdl.handle.net/11427/16225.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentMRC/UCT Receptor Biology Research Groupen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Munro et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMagnetic resonance imagingen_ZA
dc.subject.otherHysterectomyen_ZA
dc.subject.otherUterusen_ZA
dc.subject.otherUltrasound imagingen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherMyometriumen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherPermeabilityen_ZA
dc.titleQuantitative serial MRI of the treated fibroid uterusen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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