Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism

Abstract 

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17β-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This review evaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal women. In a 1-year, large-scale, randomised, controlled trial, E2 1mg/DRSP 2mg significantly decreased mean body weight by 1.2kg versus baseline (P<0.001), whereas patients receiving E2 1mg gained weight. E2 1mg/DRSP 2mg also significantly lowered mean systolic blood pressure (SBP) by 9.0mmHg from baseline (P<0.05) versus 3.7mmHg in the E2 1mg group (P=0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium ≥5.5meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2mg combined with E2 1mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic post-menopausal women.

Keywords: Progestogen, Hormone replacement therapy, Drospirenone, Post-menopausal women, Hypertension