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

Evidence-based Cardiology
stopped short of Its planned enrollment of 351.when the Data
and Safety Board determined that there was no difference
between, treatment groups During the first 48 hours the
mean number of ischemic episodes per patient recorded by
ambulatory ECG monitoring was 0-74, 0-6, and 0-74 in the
estrogen, estrogen plus progestin, and placebo groups respectively,
and symptomatic ischemia occurred in 39%, 52%, and
42%. Inhospital incidence of refractory lschearla, death,
myocardial infarcton, and revascltarization procedures were
similar in the three groups (Table 20.4). The groups did not
differ at 21 days for Ischemla, or at 6 months for clinical
events The authors cite several possible reasons for the failure
of the estrogen therapy to improve Ischemla: lack of functional
estrogen receptors in advanced lesions or with age,
countervailing adverse effects of estrogen on thrombosis or
inflammation, and the fact that participants almost uniformly
received standard anti-ischernia therapy (including heparin,
aspirin, ,3 blockers, and nitroglycerin). The numbers of
ischemlc episodes were also lower than anticpated in the
power calculations. From this study It would appear that
acute estrogen therapy is not a useful addition to the standard
therapy for acute coronary syndromes.
HERS is a landmark study, as it represents the first stbstantive
test of the hypothesis that hormone therapy prevents
coronary events in women with existing disease
(Table 20.1 ).4 The 2763 postmenopausal women aged
44-79 who enrolled all bad established CAD and had not
had a hysterectomy. They were randomized to CEE
0-625 mg/day plus MPA 2-5 mg/day or to placebo. The hormones
Induced the expected lipid changes, reducing LDL
cholesterol by I I%, raislng HDL cholesterol by 10%. and
raising triglycerides by 8% compared to placebo. Over the
average study duration of 4-1 years there was no net benefit
for the principal outcome of CHD (non-fatal myocardial
infarction plus coronary death) with 172 cases in the
placebo group and 176 cases un the active treatment group.
187
However, in the first year of HERS there was a nominally
sIgniffcaritflP< 0-05) 52% excess of coronary events in the
treatment group compared to the placebo group (Figure 20.4).
In the second year there was no difference in event rates
and thereafter there was a trend towards a reduction in the
active treatment group, mainly due to a reduction in nonfatal
myocardial infarction. The trend for coronary heart
disease risk over time was significant (P- 0-009). However,
it should be noted that the significance of the trend
depended on the adverse direction of events In the first year,
and that events after the first year were recorded in survivors
of the first year (that Is, after the first year the ians
were no longer bIlanced). There was no benefit for any other
cardiovascular outcome, including angina or revasculartizadon
procedures. Other important findings were a significant
increase in venous thromboembollsm and a marginally
significant increase in gallbladder disease (84 in hormone
OveralCMDI 1H
War 2
Year 3
waor 4+s1 _
U US 1 1-5 2 25
Relativ hazard (95% Cl)
FIgure 20.4 Relative hazard and 95% confidence intervals
for CHD in HERS over the entire trial duration and by year
since randomization 5