Effects of drospirenone on cardiovascular markers in human aortic endothelial cells.
OBJECTIVE
The effect of the new progestogen drospirenone on biochemical markers in terms of cardiovascular effects was investigated in the presence and absence of aldosterone and compared to progesterone and the progestogens medroxyprogesterone acetate (MPA) and promegestone (R5020), and the antimineralocorticoid spironolactone.


METHODS
Human female aortic endothelial cells were used for the experiments. The progestogens were tested alone at 0.1 and 10 micromol/l and in combination with aldosterone at a concentration of 10 micromol/l. The adhesion molecule E-selectin, the chemokine monocyte attracting protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were chosen as markers.


RESULTS
In combination with aldosterone, spironolactone, drospirenone, progesterone and R5020 were able to inhibit the aldosterone-induced increase in MCP-1 concentration, the effect being greatest for spironolactone. In contrast, MPA did not show any significant effect. For E-selectin, similar results were found; however, R5020 and MPA were not able to act antagonistically. Spironolactone, drospirenone and progesterone were able to significantly reduce the aldosterone-induced stimulation of PAI-1. For MPA and R5020, no significant effect was found.


CONCLUSIONS
The new progestogen drospirenone seems to have favorable effects on the cardiovascular system due to its antimineralocorticoid property. Clinical studies must prove the results of this in vitro experiment.
Seeger
H
H
University Women's Hospital, Section of Endocrinology and Menopause, Tuebingen, Germany.
Wallwiener
D
D
Mueck
A O
AO
D000293:Adolescent; D000450:Aldosterone / Q000494:pharmacology; D000736:Androstenes / Q000494:pharmacology*; D001011:Aorta; D015415:Biomarkers / Q000032:analysis*; D002316:Cardiotonic Agents; D002319:Cardiovascular System / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D003331:Coronary Vessels; D019040:E-Selectin / Q000032:analysis; D042783:Endothelial Cells / Q000737:chemistry* / Q000187:drug effects; D005260:Female; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D013148:Spironolactone / Q000494:pharmacology
D000736:Androstenes; D015415:Biomarkers; C111835:CCL2 protein, human; D002316:Cardiotonic Agents; D018932:Chemokine CCL2; D019040:E-Selectin; D000451:Mineralocorticoid Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; D045167:Progesterone Congeners; D013148:Spironolactone; D000450:Aldosterone; D011374:Progesterone; D011397:Promegestone; C035144:drospirenone