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

Evidence-based Cardiology
Cerebravascular disease
Primary prevention
Because stroke may be fatal, and often leaves the survivors
cognitively and functionally Impaired, primary prevention is
of the greatest importance
Observational studies
As reviewed elsewhere, the data for stroke are less
consistent than those for CHD. 57 Five case-control studies
of risk for Incidence of all stroke or ischemic stuke renvrted
essentially null results, and six of 16 Intemally controlled
cohort studies reported a significant reduction in risk while
two reported significantly increased risk among hormone
users. Data on stroke subtypes are scanty and variable.
Among current users in five cohort studies, three studies
found essentially no effect on ischemic stroke while one
each found an increased risk and the other a decreased risk.
Similarly, the data on duration and type of hormone therapy
(estrogen alone or combined with progestin) are variable.
Data for thromboembolk, intracerebral hemorrhage, and
subarachnoid hemorrhage stroke subtypes are very scanty.
A meta-analysis of stroke studies suggested that, in aggregate,
estrogen users had the same risk for all incident
strokes as non-users; however, this meta analysis antedated
the most recent data from the large Nurses' Health Study. 9
Examination of the 20 year follow up data from the Nurses'
Health Study is not entirely reassuring, The relative
risk for all strokes (767 strokes during 808825 personyears)
in current hormone users compared to never users
was I *13 (95% Cl 0-94-1-35), but for ischemic strokes (432
casesl the relative risk was somewhat higher (1-26, 95% Cl
1-00-1-61). Furthermore, for all strokes and for ischemlc
strokes there was a significant Increase in relative risk at the
189
usual dose of 0-625 ml, with a further increase at the higher
dose-eF 1-.25 mg or greater (Figure 20.5). For example, at
the most commonly used dose of 0-625 mg/day the relative
risk for all stroke was 1-35 (95% Cl 1-08-1-68) and for
ischemic stroke It was 1-44 195% Cl 1-07-1-931. The assoclation
of stroke with hormone use was stronger in women
who used estrogen combined with progestIn (1-45, 95% Cl
i -I 0-1 -92) than In women who used estrogen alone (I * 1-8,
95% Cl 0-95-1-46). There was no excess of strokes in past
users. Unlike in CHD, duration of hormone therapy did not
appear to influence the risk for stroke (Figure 20.5).
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at ycr
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ho 2-49 Y-.O;
tsy s-a-a ymm
O ruang .trd ,, o-3ve <
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0 0-25 0.50-75 1125 1.51-75 2 225 2s
re.ts0 e1a ask5C)
Figure 205 Relative risks and 95% confidence intervals to.
stroke by duration and dose of current hormone use in the
Nurses Health Stud 2 '
Data for fatal stroke are somewhat more consistent across
studies In suggesting an association with reduced risk In current
users. Of nine internally controlled cohort studies,
there war a signifclanttl reduced rtrt in three, 2nd v.ar
exception the point estimates for the remaining six studies
were below unity.56
Clinical trials with surrogate outcomes
A randomized placebo-controlled trial of oral estradiol in
202 (199 with evaluable outcomes) healthy postmenopausal
women aged 46-80 years found that the rate of progression
of carotid intima media thickness (IMT) over 2 years was
lower in those taking unopposed estradiol than in those on
placebo (P= 0-0 46 ).58 Adherence to study medications was
very good (95% in estradlol group and 92% In placebo
group). Per protocol, 122 participants received lipid lowering
medications (primarily statins) because their LDL
cholesterol values exceeded l bOmg/di. The numbers were
similar in the estradiol and placebo groups. The participants
in the estmAdol group who received lipid lowering medications
towered their LDL cholesterol levels by 20%, compared
to IS-1 % change In the placebo group (P= 0-02), and
both estradiol and placebo groups experienced some regression
of Intima media thickness. In the 77 participants who
did not receive lipid-towering therapy, estradiol lowered
LDL cholesterol by 10-5% compared to I -I % in the placebo