web.med/why would Estrogen agonist promote thrombosis?:
Raloxifene is approved for the prevention and treatment of
osteoporosis in postmenopausal women.
It is a mixed estrogen agonist/antagonist
formerly known as a SERM
(selective estrogen receptor modulator).
While side effects are not common, they include hot flashes,
leg cramps and deep vein thrombosis (blood clots).
how is Evista promoting venous thromboembolism?:
. increased incidence of venous thromboembolism
is the main concern of raloxifene therapy.
Old age is risk factors for thromboembolic events
reaching approximately 0.5% a year
at the age of 80 (Ageno et al 2006).
Over 5 years that could mean 3%–7% risk
and over 10 years, up to possibly 15%
likelihood of a thrombosis.
Other risk factors for thrombosis are
obesity, inflammatory diseases .
[ obesity itself is an inflammatory disease,
and Evista apparently promotes obesity .]
. so inflammation may be from Evista's obesity,
what about Evista's effect on estrogen function?
estrogen's relation to inflammation:
. there is a paradox with respect to
the immune system modulating role of estrogens.
[ the immune reactions are a major source
of inflammation .]
. in several animal models,
some estrogens suppress inflammation;
but in human chronic autoimmune diseases
we also see proinflammatory effects .
. the effects of estrogens are dependent on:
1) the immune stimulus (foreign antigens or autoantigens)
and subsequent antigen-specific immune responses
(e.g., T cell inhibited by estrogens vs. activation of B cell);
2) the cell types involved
during different phases of the disease;
3) the target organ with its specific microenvironment;
4) timing of 17beta-estradiol administration
in relation to the disease course
(and the reproductive status of a woman);
5) the concentration of estrogens;
6) the variability in expression of
estrogen receptor alpha and beta
depending on the microenvironment and the cell type;
7) intracellular metabolism of estrogens
leading to biologically active metabolites
with quite different anti- and proinflammatory function.
. a uniform concept as to the action of estrogens
cannot be found for all inflammatory diseases
due to the enormous variable responses
of immune and repair systems.