Bioidentical Hormones - U.S. Senate Special Committee on Aging

10000
isoor
i I
ea '°
a
wan
20-24 25-3 25-4 45-4 55-r4 65-74 75-84 85.
Figure 20.2 Annual mortality rtes for CHD by age for US
men and women on a sereHogarithmic scale
a decrease in fibrinogen level 7 ] while others are potentially
unfavorable (for example, an increase in factor VI1
t ' 5 ', and
the net effect of estrogen on coagulation is uncertain.
Siaisiarly, some effects on markers of inflammation are
potentially unfavorable (for example, Increases in C-reactive
protein) and others favorable (for example, decreases in vascular
endothellal adhesion molecales)."" '2 Other potential
influences of estrogen on vascular biology include direct
effects on the vessel wall, which improve blood flow,1l3.1
and andoxidant properties that may slow the early stages of
atherosclerosis." It should be noted that many, but not all,
of the biologic effects of estrogen are counteracted by the
progestins, which are now routinely prescribed in combinaton
swith estrogen in women with Intact utenis.7-
Thus, there is a plethora of potential mechanisms by which
estrogen may reduce the risk of CHD. 16 Unfortunately, the
existence of mechanisms does not necessy translate into
clinical benefit A treatment that has a favorable effect on an
intermediate mechanism may decrease the incidence of target
clinical events, or may surn out to have no effect, or may actu
ally increase the event rates. The treatment may also have
unanticipated adverse effects on other clinical events. 1 For
example, a number of early lpid lowering drugs, such as thyroxin
and estrogen, were abandoned after It was found that,
although these drugs decrease cholesterol levels, they also
increase the cardiovascular morbidity and mortality in men."'
*. .
* l a n blendl~ "'t4S glio -,i F N i*Hi-
: e e ~ a m a u :qd d~~
182
Postmenopausai hormone therapy and cardiovascular disease
Coronary heart disease
Throughout this chapter, the term postmenopausal hormone
therapy (sometimes shortened to hormone therapy)
is used to describe the use of estrogen or estrogen plus a
progestin In postmenopausal women. The term hormone
replacement therapy Is not used, because this term Implies
a judgment that postmenopausal women suffer from a
hormone "deficiency" that needs treatment.
More than 30 observational studies have suggested that
women who are taking estrogen appear to have a lower risk
of heart disease, and several have shown similar apparent
risk reductions for estrogen when it is used in combination
with progestin.'e-2 3 Only a few key studies will be reviewed
In detail, since they Illustrate sufficiently the findings from
observational studles, and their Limitations. 'Primary prevention"
studies are those in which women with prevalent
coronary artery disease (CAD) were removed from the
cohort, while 'secondary prevention' studies followed
only those women with a history or other evidence of CAD
at baseline. The growing body of evidence from clinical
trials with surrogate outcomes and clinical trials, with
'hard" clinical outcomes for secondary prevention, will be
reviewed in detail. Thus far, these secondary prevention
trials have failed to confirm the cardiovascular benefit
predicted from observational studies, and in fact the
trials suggest that there is likely to be harm in the first few
months to years after Initiation of hormone therapy.
Substantive data from primary prevention trials have yet to
be published.
Primary prevention
Obsevatronal shAdies
With the exception of the initial report from Framingham
on this issue, all the observational studies of healthy
postmenopausal women comparing hormone users with
non-users described an association of hormone use (partcularly
current hormone use) with lower risk for CHD.' 5 - 24
However, as reviewed elsewhere, the consistency of these
results may be due to powerful systematic biases in observational
studies, which may lead to an overestimation of
benefit and an underestimation of harm associated with
hormouie use.25X,
The Nurses' Health Study is representative of the observational
studies, and the women In this study comprise one
of the largest and best studledcohorts in the USA. 21 The
1976 baseline examination Included 121 700 nurses aged
30-55 years of whom 21 726 were postmenopausal. With
the passage of time a progressively larger proportion entered
the menopause and these women contributed data to a
series of papers on the associations between menopause,
hormone therapy, and cardiovascular disease. Data on