Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on blood pressure and potassium balance in hypertensive postmenopausal women receiving hydrochlorothiazide.
OBJECTIVE
Drospirenone (DRSP), a spironolactone analog with aldosterone antagonist activity, is a novel progestogen developed for use as hormone therapy in postmenopausal women in combination with 17beta-estradiol (E2). DRSP/E2 lowers blood pressure when used alone in hypertensive postmenopausal women or when administered concomitantly with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. DRSP/E2 has not been studied in combination with the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of 3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when added to existing therapy with 25 mg HCTZ in postmenopausal women with established stage I hypertension.


METHODS
This was a single-center, double-blind, randomized, placebo-controlled, two-treatment, two 4-week treatment period crossover study in 36 postmenopausal women with stage I hypertension maintained on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring. Safety monitoring included serum potassium (mEq/L) and adverse events.


RESULTS
Mean systolic and diastolic blood pressures by 24-hour ambulatory blood pressure monitoring were reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2 mEq/L less with DRSP/E2 than placebo, suggesting a potassium-sparing effect. The most frequently observed adverse events with DRSP/E2 were vaginal bleeding and breast tenderness, which were attributable to the hormone therapy.


CONCLUSIONS
DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women. In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced potassium loss.
Preston
Richard A
RA
Division of Clinical Pharmacology and Pharmacokinetics Clinical Research Center, Department of Medicine, Miller School of Medicine, University of Miami, FL 33136, USA. rpreston@med.miami.edu
Norris
Paul M
PM
Alonso
Alberto B
AB
Ni
Pingping
P
Hanes
Vladimir
V
Karara
Adel H
AH
D000368:Aged; D000736:Androstenes / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000517:prevention & control; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D017698:Postmenopause / Q000187:drug effects; D011188:Potassium / Q000097:blood; D016896:Treatment Outcome
D000736:Androstenes; D000959:Antihypertensive Agents; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D006852:Hydrochlorothiazide; C035144:drospirenone; D011188:Potassium