Abstract
We previously published the DexFEM trial, which showed that in women with heavy menstrual bleeding (HMB), oral dexamethasone reduces menstrual blood loss. Here, we report a pharmacodynamic analysis exploring the likely mechanism for this effect. We studied oral dosing with dexamethasone during the mid-luteal phase of two menstrual cycles (1.5 mg daily, 5 days) in five women with HMB (six recruited aged 41–50 years, one withdrew before treatment). Steroid hormones were profiled in serum and endometrium by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We found that following oral dosing, dexamethasone reached the endometrium and that, compared to the preceding control cycle, cortisol (active), cortisone (inactive) and intermediate 11-deoxycortisol were reduced in all samples assessed, both endometrial (n = 4) and serum (n = 5). Concentrations of androgens, androstenedione and testosterone were reduced in serum but not in all tissue samples. This proof-of-concept pharmacodynamic study supports the inference that dexamethasone is effective in HMB by altering endometrial glucocorticoid concentrations.