II-204 ZDRAV VESTN 2003; 72: SUPPL II
VPLIV NADOMEŠČANJA ESTRADIOLA NA
OZNAČEVALCE VNETJA, KOAGULACIJO IN
FIBRINOLIZO
THE INFLUENCE OF ESTRADIOL REPLACEMENT THERAPY IN MARKERS OF
INFLAMMATION, COAGULATION AND FIBRINOLYSIS
Branka Žegura1, Irena Keber2, Miran Šebeštjen2, Elko Borko1, Wolfgang Koenig3
1 Klinični oddelek za ginekologijo in perinatologijo, Učna bolnišnica Maribor, Ljubljanska 5, 2000 Maribor
2 Klinični oddelek za žilne bolezni, Klinični center, Zaloška 7, 1525Ljubljana
3 Oddelek za interno medicino II – kardiologija, Medicinski center univerze v Ulmu, Ulm, Nemčija
Key words: estrogen replacement therapy; markers of inflam-
mation; coagulation and fibrinolysis
Abstract – Background. Estrogen replacement therapy (ERT)
has been found to be associated with increased cardiovascu-
lar risk in the first year after initiation of ERT. We compared
the effects of oral and transdermal estradiol (E2) replacement
therapy on markers of inflammation, coagulation and fibri-
nolysis in a randomized double-blind trial.
Methods. Fortythree healthy women were randomized six
weeks after surgically induced menopause to receive treat-
ment with either oral or with transdermal E2 over a period of
28 weeks. At baseline and after 28 weeks, levels of serum li-
pids and lipoproteins, and markers of coagulation, fibrinoly-
sis, and inflammation were determined.
Results. Among fibrinolytic parameters, oral E2 shortened
euglobulin clot lysis time (p<0.05), reduced tissue type pla-
sminogen activator antigen (p = 0.01), and plasminogen ac-
tivator inhibitor activity (p<0.05). Among coagulation para-
meters, both routes of E2 replacement decreased fibrinogen
levels (p = 0.002 for oral and p = 0.007 for transdermal E2).
Oral E2 resulted in an increase in C-reactive protein from
2.15 (0.71–4.05) to 3.41 (1.12–5.92) mg/l (p = 0.04), while
transdermal E2 showed no effect. Levels of serum amyloid A,
IL-6 and TNF-á did not change significantly after oral and
transdermal E2.
Conclusions. Oral E2 significantly improved the lipid profile,
while transdermal E2 had a less pronounced effect. Both oral
and transdermal E2 significantly reduced fasting glucose.
Oral E2 was associated with a pro-inflammatory response,
but at the same time improved fibrinolytic capacity, showed
no pro-coagulatory effects, and acted beneficially on lipids
and lipoproteins. There was no influence of transdermal E2
on markers of coagulation activation, fibrinolysis and inflam-
mation, but it decreased fibrinogen levels significantly. Furt-
her studies are needed to explore the clinical relevance of the-
se observations.
Ključne besede: nadomeščanje estrogenov; označevalci vnet-
ja; koagulacija in fibrinoliza
Izvleček – Izhodišča. Hormonsko nadomestno zdravljenje po-
vezujejo s povečanim tveganjem za srčno-žilne bolezni v pr-
vem letu po začetku zdravljenja. V randomizirani raziskavi
smo primerjali vpliv peroralnega in transdermalnega nad-
omeščanja estradiola na kazalnik vnetja, na koagulacijo in
fibrinolizo.
Metode. Triinštirideset zdravih preiskovank smo 6 tednov po
kirurško povzročeni menopavzi naključno razdelili v dve sku-
pini. V prvi skupini smo preiskovankam estradiol nadome-
ščali peroralno, v drugi pa transdermalno. Na začetku, 6 te-
dnov po operaciji in po 28 tednih peroralnega ali transder-
malnega nadomeščanja estradiola smo opravili klinični pre-
gled in laboratorijske krvne analize.
Rezultati. Med fibrinolitičnimi parametri se je po peroralnem
nadomeščanju skrajšal čas evglobulinske lize (p<0,05), zni-
žala raven t-PA (p = 0,001), zmanjšala aktivnost PAI-1
(p<0,05). Med koagulacijskimi parametri se je po obeh obli-
kah nadomeščanja estradiola znižala raven fibrinogena
(p = 0,002 za peroralno nadomeščanje in p = 0,007 za trans-
dermalno nadomeščanje). Med označevalci vnetja je prišlo
do pomembnega porasta ravni CRP samo po peroralnem
nadomeščanju z 2,15 (0,71–4,05) na 3,41 (1,12–5,92) mg/l
(p = 0,04). Ravni serumskega amiloida A, interlevkina-6 in
faktorja tumorske nekroze alfa se niso pomembno spremeni-
le po nobeni od obeh oblik nadomeščanja. Peroralno nadome-
ščanje estradiola je pomembno izboljšalo lipidni profil, vpliv
transdermalnega nadomeščanja je bil manjši. Obe obliki na-
domeščanja sta pomembno znižali raven krvnega sladkorja.
Zaključki. V naši raziskavi je peroralno nadomeščanje estra-
diola kazalo provnetni učinek, po drugi strani je izboljšalo
fibrinolizo in ni imelo prokoagulantnega učinka. Ugodno je
delovalo tudi na krvne lipide in lipoproteine. Transdermal-
no nadomeščanje estradiola ni vplivalo na označevalce vnet-
ja, koagulacijo in fibrinolizo, vendar je prišlo do ugodnega
znižanja ravni fibrinogena.