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Low-dose continuous combinations of hormone therapy and biochemical surrogate markers for vascular tone and inflammation: transdermal versus oral application.

Mueck, Alfred; Genazzani, Andrea; Samsioe, Göran LU ; Vukovic-Wysocki, Ivana and Seeger, Harald (2007) In Menopause 14(6). p.978-984
Abstract
Objective: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri.



Design: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 [mu]g E2 and 125 [mu]g NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1,... (More)
Objective: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri.



Design: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 [mu]g E2 and 125 [mu]g NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin.



Results: Significant decreases were found for P-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for both hormone therapy (HT) regimens compared with baseline. Matrix metalloproteinase-9 was increased only by oral HT. The urinary concentrations of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane metabolite, and the serotonin metabolite were significantly increased for both HT application modes, although the oral treatment showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was increased only by the oral regimen.



Conclusions: Low-dose transdermal and oral HTs using E2 and NETA elicit favorable effects on cardiovascular biochemical markers. For most markers the magnitude of changes found were similar with respect to baseline; however, in some cases oral HT led to a significantly greater change, whereas in other cases the transdermal formulations seemed to provide greater benefits. Whether these differences may be attributed to the different administration routes or to different pharmacokinetic properties remains an open question. Overall low-dose transdermal HT seems to provoke the same benefit on the cardiovascular system as oral HT, as suggested by the results on vascular markers. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Menopause
volume
14
issue
6
pages
978 - 984
publisher
Lippincott-Raven Publishers
external identifiers
  • wos:000250945000007
  • scopus:36048942013
ISSN
1530-0374
DOI
10.1097/gme.0b013e318054e2e7
language
English
LU publication?
yes
id
0dd222f1-10c1-4698-80fa-505f7b4eb3ee (old id 539536)
alternative location
http://www.menopausejournal.com/pt/re/menopause/abstract.00042192-200714060-00007.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17595593&dopt=Abstract
date added to LUP
2008-07-30 12:41:22
date last changed
2017-08-20 03:41:09
@article{0dd222f1-10c1-4698-80fa-505f7b4eb3ee,
  abstract     = {Objective: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri.<br/><br>
<br/><br>
Design: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 [mu]g E2 and 125 [mu]g NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin.<br/><br>
<br/><br>
Results: Significant decreases were found for P-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for both hormone therapy (HT) regimens compared with baseline. Matrix metalloproteinase-9 was increased only by oral HT. The urinary concentrations of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane metabolite, and the serotonin metabolite were significantly increased for both HT application modes, although the oral treatment showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was increased only by the oral regimen.<br/><br>
<br/><br>
Conclusions: Low-dose transdermal and oral HTs using E2 and NETA elicit favorable effects on cardiovascular biochemical markers. For most markers the magnitude of changes found were similar with respect to baseline; however, in some cases oral HT led to a significantly greater change, whereas in other cases the transdermal formulations seemed to provide greater benefits. Whether these differences may be attributed to the different administration routes or to different pharmacokinetic properties remains an open question. Overall low-dose transdermal HT seems to provoke the same benefit on the cardiovascular system as oral HT, as suggested by the results on vascular markers.},
  author       = {Mueck, Alfred and Genazzani, Andrea and Samsioe, Göran and Vukovic-Wysocki, Ivana and Seeger, Harald},
  issn         = {1530-0374},
  language     = {eng},
  number       = {6},
  pages        = {978--984},
  publisher    = {Lippincott-Raven Publishers},
  series       = {Menopause},
  title        = {Low-dose continuous combinations of hormone therapy and biochemical surrogate markers for vascular tone and inflammation: transdermal versus oral application.},
  url          = {http://dx.doi.org/10.1097/gme.0b013e318054e2e7},
  volume       = {14},
  year         = {2007},
}