Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism.
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 17beta-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 1 mg/DRSP 2 mg significantly decreased mean body weight by 1.2 kg versus baseline (P<0.001), whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from baseline (P<0.05) versus 3.7 mmHg in the E2 1 mg group (P=0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium > or =5.5 meq/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 2 mg combined with E2 1 mg 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.
Palacios
Santiago
S
Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain. spalacios@institutopalacios.com
Foidart
Jean-Michel
JM
Genazzani
Andrea R
AR
D000736:Androstenes / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists; D045167:Progesterone Congeners / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects
D000736:Androstenes; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D045167:Progesterone Congeners; C488382:estradiol-drospirenone combination; D004958:Estradiol; C035144:drospirenone