2015-01-01

why would Estrogen agonist promote thrombosis?

web.med/why would Estrogen agonist promote thrombosis?:
2014.10.11: 
Raloxifene (Evista)
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).
Side Effects
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.