Luteal phase oral dexamethasone administration alters the endometrial steroid milieu

We previously published the DexFEM trial which showed in women with heavy menstrual bleeding oral dexamethasone reduces menstrual blood loss. Here, we report 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 5 women with HMB (6 recruited aged 41-50 years, 1 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 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, androstenendione 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.