WOMEN 'S HEALTH AND MENOPAUSE : - National Heart, Lung ...

Overall, these studies show that oral CEEs plus
MPA in combination with a statin is complementary,
in that the statins are better at lowering LDL
cholesterol levels, the hormones are better at raising
HDL cholesterol levels, and the effects on
triglycerides cancel each other: thus the combination
yields the most optimal lipid profile. The combination
is only modestly additive, that is, hormones
add little to the LDL-lowering effect of statins, and
statins add only modestly to the HDL-raising
effect of hormones. Hormones reduce Lp(a) levels,
while statins do not. No studies have yet been published
comparing other types and routes of administration
of HRT combined with a statin.
In one study, 155 28 women were randomized to
continuous equine estrogen (0.625 mg daily), simvastatin
10 mg, and their combination daily for 6
weeks. As shown in the previous studies, all therapies
lowered total and LDL cholesterol levels from
baseline, with a greater effect on LDL cholesterol
from simvastatin and from the combination of
HRT and simvastatin. This study also assessed the
vascular effects of this therapy; flow mediated
dilatation of the brachial artery improved on CEE,
simvastatin, and continuous equine estrogen combined
with simvastatin, and this was similar among
the therapies. Only therapies including CEE lowered
levels of PAI–1 and the cell adhesion molecule
E-selectin. Only therapies including estrogen
improved markers of fibrinolysis and vascular
inflammation. Thus, it may be that such a combination
will be synergistic in vascular protection.
4.1.4 Coagulation Factors
The effects on coagulation factors are complicated,
diverse, and contradictory. For example, lowering
of fibrinogen and PAI–I could be counterbalanced
by increases in factor VII and decreases in
antithrombin III. In general, it appears that estrogen
is procoagulant but, at the same time, profibrinolytic.
156 The net effect is likely to be procoagulant,
as evidenced by the observational studies and
the HERS clinical trial (see elsewhere). However,
the net effect of estrogen on coagulation can
depend on the form of estrogen used and on the
dose, route, and duration of therapy. There may be
critical differences between oral and transdermal
delivery of estrogen. In contrast to oral administration,
transdermal estrogen does not result in any
measurable perturbation of coagulation factors. 156
4.2 Hormone Use and Prevention of CHD Risk
Observational studies comparing current hormone
users with non-users have shown consistent reductions
in CHD risk of 35–50 percent. In the Nurses’
Health Study, the risk reduction was seen at the
most commonly used dose of CEEs (0.625
mg/day). 157 There appeared to be a similar risk
reduction at the lower dose of 0.3 mg/day, but this
was not statistically significant. At higher doses,
there was no apparent benefit. The findings from
these observational studies have been important in
promoting the belief that HRT prevents CHD.
However, the findings have to be viewed with caution
because several
sources of potential bias
could result in an overestimation
of potential
benefits and an underestimation
of risks. 158,159
Women are approximately
half as likely as men to
receive known beneficial
These biases include therapies, such as beta-
that women who elect to blocking agents, aspirin,
take hormones are
thrombolysis, acute
healthier, and those that
remain on hormones for cardiac catheterization,
many years are by defi- percutaneous transluminal
nition good compliers
and are under medical
coronary angioplasty
surveillance. (See also (PTCA), or bypass surgery.
ch. 4 for biases in sampling.)
Thus, they would
be taking other steps to improve their health, and
early detection and treatment of risk factors would
also reduce disease risk. Furthermore, women who
stop therapy often do so because of the development
of a health condition; thus those who remain
on therapy are the healthy survivors. These biases
159