Quantitative serial MRI of the treated fibroid uterus
Millar, Robert P.; Munro, Kirsty I.; Thrippleton, Michael J.; Williams, Alistair R.W.; McKillop, Graham; Walker, Jane B.; Horne, Andrew W.; Newby, David E.; Anderson, Richard A.; Semple, Scott I.; Marshall, Ian; Lewis, Steff C.; Bastin, Mark E.; Critchley, Hilary O.D.
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.