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

Is associated with an Increased risk for recurrent events In
the short term; two of these studies provided data suggesting
a possible decreased risk in later years among the
survivors (Table 20.3).'2" This pattern of Increased risk in
U.e first year with apparently reduced risk in later years is
similar to that observed In several randomized controlled
clinical trials, notably the Heart and Estrogen/progestin
Replacement Study (HERS). 45 It should be noted that these
analyses of risk by recency of hormone use were performed
after publication of the HERS results; therefore the possibitity
of publication bias cannot be excluded.
Cinical trials with surrogate outcomes
The primary outcome of the Estrogen Replacement and
Atherosclerosos (ERA) trial was change in the angiographic
minimal diameter of coronary artery leslons.4e Women
(n = 309) with angiographically defined CAD were randomized
to one of three groups: CEE 0-625 mg, CEE 0-625 mg
plus MPA 2.5 mg, or placebo. At the end of the trial, compliance
ranged from 74% In the estrogen-only group to
84-86% in the other groups. Over the mean treatment
duration of 3-2 years, all three groups showed a decrease
in minimal coronary artery diameter and there were no
186
Postrnenopausal hormone therapy and cardiovascular disease
differences between the groups. In other words, treatment
with estrogen with or without MPA failed to arrest the progresston
of existing coronary artery lesions, even though the
estrogen and estrogen plus MPA treatments lowered LDL
cholesterol by 9-4 and 16.5%, and raised HDL cholesterol
levels by 18-8 and 14-2%, respectively. Several additional
clinical trials with anglographic outcomes are underway.
Clinical tnals
A randomized controlled clinical trial in 293 postmenopausal
women with unstable angina, aged 43-93,
failed to demonstrate benefit with estrogen or estrogen plus
progestin for reduction in number of ischemic episodes. 47
The premise of the trial was that endothellal dysfunction
with subsequent impairtent of coronary blood flow has an
Important pathophyslologic role In acute coronary syndromes,
and that reversal of the endothellal dysfunction by
estrogen would Improve the clinical outcome. Participants
received one of three study treatments within 24 hours of
the onset of symptoms an Infusion of 1-25mg of CEE followed
by oral CEE 1-25mg/day for 21 days, or an infusion
of CEE followed by oral CEE plus MPA 2-5mg/day, or an
Infusion of placebo followed by oral placebo. The trial was