title: Quantitative serial MRI of the treated fibroid uterus.
abstract: 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00746031.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kirsty I
authors.initials: KI
authors.lastname: Munro
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thrippleton
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom; Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom.
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: Williams
authors.affiliation: Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom.
authors.forename: Graham
authors.initials: G
authors.lastname: McKillop
authors.affiliation: Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Walker
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Scott I
authors.initials: SI
authors.lastname: Semple
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Marshall
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Steff C
authors.initials: SC
authors.lastname: Lewis
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom; Mammal Research Institute, University of Pretoria, Pretoria, South Africa; UCT/MRC Receptor Biology Unit, University of Cape Town, Cape Town, South Africa; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.affiliation: Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
mesh_terms: D000328:Adult; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D017697:Premenopause; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014599:Uterus / Q000187:drug effects* / Q000473:pathology*
chemical_list: D007987:Gonadotropin-Releasing Hormone