PMID- 11797164
OWN - NLM
STAT- MEDLINE
DCOM- 20020415
LR  - 20141120
IS  - 0044-4197 (Print)
IS  - 0044-4197 (Linking)
VI  - 123
IP  - 11
DP  - 2001 Nov
TI  - [Effect of tibolone on vascular markers of human female coronary arteries - 
      comparison with estradiol/norethisterone].
PG  - 648-54
AB  - OBJECTIVES: Tibolone, a synthetic norethynodrel derivative, is effective at 
      alleviating climacteric complaints and for osteoporosis prophylaxis. Concerning 
      the cardiovascular system little data are available on possible direct effects on 
      the vasculature compared with hormone replacement therapy. Since tibolone is 
      pharmacologically best comparable to an estradiol/norethisterone combination 
      (E2/NET), the aim of the present study was to compare these treatment regimens 
      with respect to their effects on human vascular cells, this being the first study 
      to investigate this question. - MATERIAL AND METHODS: Human female coronary 
      arteries were used, the most appropriate vessels for our issue in question. The 
      experiments were conducted with endothelial cells as well as smooth muscle cells. 
      Tibolone and E2/NET were tested at the concentrations 0.1, 1 und 10 microM. 
      Incubation time was 24 h for endothelial cell cultures and 7 days for smooth 
      muscle cell cultures. The effects on markers of pathophysiologically different 
      problems were studied in a comparable manner: Markers of endothelial function 
      such as prostacyclin, endothelin and plasminogen-activator-inhibitor-1 (PAI-1), 
      markers of plaque initiation such as the adhesion molecules E-Selectin, ICAM-1 
      and the monocyte attraction protein-1 (MCP-1) and markers of plaque stability 
      such as the precursor of the matrix-metalloproteinase-1 (pro-MMP-1). - RESULTS: 
      Tibolone reduced the synthesis of endothelin as well as the concentrations of 
      E-Selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers 
      varied and was in the range of 11-42 %. similar inhibitions were seen for E2/NET; 
      yet a significantly stronger inhibitory effect was found for pro-MMP-1. Moreover, 
      E2/NET also reduced concentrations of ICAM-1 and MCP-1. Concerning smooth muscle 
      cells only E2/NET was able to elicit an anti-proliferative effect. - CONCLUSIONS: 
      Tibolone can positively influence the synthesis of markers in cell cultures of 
      human female coronary artery which modulate vascular tone and which play a 
      decisive role in the various stages of atherosclerosis. In this respect estradiol 
      combined with norethisterone is as potent as tibolone, in addition this 
      combination is partially more effective and able to influence a wider range of 
      markers which are important in the early stages of atherogenesis or for the 
      stability of atherosclerotic plaques. Experimental studies such as the present 
      one are useful to explore mechanisms, but clearly cannot replace clinical 
      studies.
FAU - Mueck, A O
AU  - Mueck AO
AD  - Bereich Endokrinologie und Menopause, Universitats-Frauenklinik, Tubingen. 
      endo.meno@med.uni-tuebingen.de
FAU - Seeger, H
AU  - Seeger H
FAU - Wallwiener, D
AU  - Wallwiener D
LA  - ger
PT  - Comparative Study
PT  - English Abstract
PT  - Journal Article
TT  - Effekte von Tibolon auf vaskulare Marker menschlicher weiblicher Koronararterien 
      - Vergleich mit Estradiol/Norethisteron.
PL  - Germany
TA  - Zentralbl Gynakol
JT  - Zentralblatt fur Gynakologie
JID - 21820100R
RN  - 0 (Norpregnenes)
RN  - 4TI98Z838E (Estradiol)
RN  - FF9X0205V2 (tibolone)
RN  - T18F433X4S (Norethindrone)
SB  - IM
MH  - Cell Division/drug effects
MH  - Coronary Vessels/*drug effects/pathology
MH  - Culture Techniques
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*drug effects/pathology
MH  - Estradiol/*pharmacology
MH  - *Estrogen Replacement Therapy
MH  - Female
MH  - Humans
MH  - Muscle, Smooth, Vascular/drug effects
MH  - Norethindrone/*pharmacology
MH  - Norpregnenes/*pharmacology
MH  - Vascular Resistance/drug effects
EDAT- 2002/01/18 10:00
MHDA- 2002/04/16 10:01
CRDT- 2002/01/18 10:00
PHST- 2002/01/18 10:00 [pubmed]
PHST- 2002/04/16 10:01 [medline]
PHST- 2002/01/18 10:00 [entrez]
AID - 10.1055/s-2001-19517 [doi]
PST - ppublish
SO  - Zentralbl Gynakol. 2001 Nov;123(11):648-54. doi: 10.1055/s-2001-19517.