PMID- 12082363
OWN - NLM
STAT- MEDLINE
DCOM- 20020917
LR  - 20191106
IS  - 1072-3714 (Print)
IS  - 1072-3714 (Linking)
VI  - 9
IP  - 4
DP  - 2002 Jul-Aug
TI  - Medroxyprogesterone acetate versus norethisterone: effect on estradiol-induced 
      changes of markers for endothelial function and atherosclerotic plaque 
      characteristics in human female coronary endothelial cell cultures.
PG  - 273-81
AB  - OBJECTIVE: Progestin addition to estradiol (E(2)) replacement therapy may lead to 
      a deterioration of beneficial effects on the vasculature. The effect of the two 
      clinically most common progestins, medroxyprogesterone acetate (MPA) and 
      norethisterone (NET), during continuous combination with E(2) on the synthesis of 
      markers for coronary endothelial function, atherosclerotic plaque initiation, and 
      plaque formation was investigated in human female vascular cell cultures and 
      compared with that of E(2) alone. DESIGN: Endothelial cell cultures from human 
      female coronary arteries were used to evaluate the effect of progestin addition 
      to E(2) on the production of the following endothelial markers: prostacyclin, 
      endothelin, plasminogen activator inhibitor-1, E-selectin, intercellular adhesion 
      molecule-1, monocyte chemoattractant protein-1 (MCP-1), and the precursor of 
      matrix metalloproteinase-1 (pro-MMP-1). E(2) was tested at 0.1 microM, 1 microM, 
      and 10 microM alone and in equimolar combinations with MPA or NET. The markers 
      were determined by enzyme immunoassays in the cell supernatant. RESULTS: E(2) 
      induced a significant increase of endothelial prostacyclin production and was 
      able to significantly decrease the synthesis of endothelin, plasminogen activator 
      inhibitor-1, E-selectin, and intercellular adhesion molecule-1. Neither MPA nor 
      NET addition negatively interfered with these E(2)-induced benefits. However, MPA 
      antagonized the E(2)-induced significant reduction of MCP-1 synthesis, with the 
      difference between both progestins being significant (p < 0.01). Interestingly, 
      an enhancement of the positive E(2)-effect on pro-MMP-1 production was observed 
      by the addition of both MPA and NET (p < 0.01). CONCLUSION: E(2) can positively 
      influence various markers of endothelial function. Addition of MPA or NET can 
      elicit different effects, which has been demonstrated for the first time in human 
      coronary cell cultures. No impact was found on markers representing primarily 
      vasotonus and thrombogenicity. In terms of MMP-1, which is crucial for 
      atherosclerotic plaque stability, an enhancement of the beneficial E(2) effect 
      was observed. However, regarding MCP-1, contrary effects of progestins cannot be 
      excluded. This indicates that progestins may differ in their effects, 
      particularly in the early stages of atherosclerosis, which has also been 
      supported by other studies.
FAU - Mueck, Alfred O
AU  - Mueck AO
AD  - Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, 
      University of Tuebingen, Tuebingen, Germany. endo.meno@med.uni-tuebingen.de
FAU - Seeger, Harald
AU  - Seeger H
FAU - Wallwiener, Diethelm
AU  - Wallwiener D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Menopause
JT  - Menopause (New York, N.Y.)
JID - 9433353
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (E-Selectin)
RN  - 0 (Endothelins)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - T18F433X4S (Norethindrone)
SB  - IM
MH  - Biomarkers/*analysis
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis
MH  - Confidence Intervals
MH  - Coronary Artery Disease/drug therapy/*physiopathology
MH  - Coronary Vessels/cytology/drug effects
MH  - E-Selectin/analysis/drug effects
MH  - Endothelins/analysis/drug effects
MH  - Endothelium, Vascular/cytology/*drug effects
MH  - Epoprostenol/analysis
MH  - Female
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/analysis/drug effects
MH  - Matrix Metalloproteinase 1/analysis/drug effects
MH  - Medroxyprogesterone Acetate/*pharmacology
MH  - Norethindrone/*pharmacology
MH  - Probability
MH  - Sensitivity and Specificity
EDAT- 2002/06/26 10:00
MHDA- 2002/09/18 10:01
CRDT- 2002/06/26 10:00
PHST- 2002/06/26 10:00 [pubmed]
PHST- 2002/09/18 10:01 [medline]
PHST- 2002/06/26 10:00 [entrez]
AID - 10.1097/00042192-200207000-00008 [doi]
PST - ppublish
SO  - Menopause. 2002 Jul-Aug;9(4):273-81. doi: 10.1097/00042192-200207000-00008.