This study builds on previous research which has provided compelling evidence that deficient
activity of glucocorticoids in the endometrium is a cause of increased menstrual bleeding.
This study aims to demonstrate that a glucocorticoid (dexamethasone), already in common use
for other conditions, (eg to treat medical conditions such as asthma and rheumatoid arthritis
in early pregnancy), will reverse the endometrial glucocorticoid deficiency and as a result
reduce menstrual blood loss.
The study is in two stages, a 12 month workup stage and a 3 year, response adaptive,
dose-finding randomised controlled trial. The first stage involves two workup clinical
studies to gather preliminary safety and efficacy data from first-in-Heavy Menstrual Bleeding
use of oral dexamethasone. They will also provide methodological data for a series of
simulation studies to determine a robust adaptive trial design specification.
Workup study 1: is unblinded, six patients will be given Dexamethasone (0.75mg twice daily)
for 5 days during two consecutive menstrual cycles and will have an endometrial biopsy and
MRI on two occasions (in a nontreated cycle, and the second of the cycles treated with
Dexamethasone). Workup study 2Íž is a doubleblind crossover trial of 14 women -2 treatment
blocks of two cycles each, with either placebo or Dexamethasone (0.75mg twice daily),
randomised to order of treatments blocks - placebo then Dexamethasone, or vice-versa.
Adaptive trial: 54 month double-blind, placebo controlled trial of 108 women to evaluate the
effect of Dexamethasone across a range of doses with the aim of identifying the optimal dose
to be studied in a subsequent Phase III trial.
Participants will be randomised to receive one of 6 active doses or placebo over 3 menstrual
cycles.
All studies will involve asking participants to complete menstrual diaries and to carry out
menstrual blood loss collections to objectively measure blood loss.
The investigators' proposed approach is novel use of synthetic glucocorticoid to "rescue"
luteal phase deficiency of cortisol, and thus improve endometrial vasculature and hence
vasoconstriction when menses commences, and thus reduce menstrual bleeding.