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safety and efficacy records. The WHI was PremPro; a second arm used only a con- angina, strokes and smoking. The adverse
supposed to definitively answer questions jugated equine estrogen (CEE), Premarin outcomes WHI attributed to hormone
about the efficacy and benefits of HRT and a third arm evaluated the effects of therapy, especially cardiovascular, could
but only created confusion and concern. calcium and vitamin D on fracture risk. very well be linked to age and pre-exist-
There were three treatment arms in WHI: Subjects in the PrePro combined synthet- ing risk factors. A reanalysis by Rossouw
the first used a combination of synthetic ic hormone arm were reported to have an et. al, published in JAMA in 2007 sepa-
hormones, Premarin plus Provera, called increased risk of breast cancer, stroke and rated WHI participants by age and found
coronary artery disease. The results from a reduced risk for coronary heart disease
the Premarin only group were less publi- in all women taking hormone therapy 10
cized but demonstrated a reduced rela- or fewer years from menopause. The only
tive risk for both breast cancer and heart statistically significant increase in cardiac
disease; the risk of thrombophlebitis was events occurred in women 20 plus years
increased. Initial news reports on the cal- postmenopause. Furthermore, the results
cium and vitamin D arm suggested no of the WHI Coronary-Artery Calcium
benefit from taking those supplements. Score Study performed after the conclu-
Subsequent analysis has determined that sion of the WHI, demonstrated a 61%
the study was poorly designed and the reduction in coronary artery calcification
initial analysis faulty. in women taking estrogen. This translates
Concerns with the WHI study design into a reduced incidence of subclinical
include the type of hormone used, dosing coronary artery disease in women receiv-
pattern, route of administration, timing of ing estrogen. Although breast cancer may
hormone usage, mean age of the partici- be the greater fear for women, 10 times
pants, and prior health status of the par- more women die from cardiovascular
ticipants. The WHI used only synthetic disease every year than breast cancer.
hormones taken orally and at a relatively As mentioned above, the WHI used
high, fixed dose. The participants were, only synthetic hormones. Synthetic estro-
on average, 63 years old and more than gens are metabolized to 4OH estrogen,
ten years beyond menopause; the crucial which has been found to be thirty-times
time to mitigate the pro-inflammatory more toxic to cellular DNA than bioi-
effects of the postmenopause transition. dentical estrogens. Synthetic progestins
Studies have demonstrated estrogen’s appear to attenuate most beneficial ef-
ability to block chronic inflammatory fects of estrogens and enhance estrogen’s
mediators, including interleukin-6, tumor proliferative effects. That may explain any
necrosis factor alpha and prostaglandin increased risk of breast cancer noted after
E2. Estrogen has also been found to have 10 or more years of synthetic hormone
significant antioxidant effects. replacement therapy.
Participants in the WHI were not ad- The synthetic hormones used in WHI,
equately prescreened for breast cancer or Premarin and PremPro are administered
subclinical atherosclerotic heart disease, orally. They are subjected to first pass
and it was reported in JAMA, the Journal through the liver resulting in increased
of the American Medical Association in production of clotting proteins and in-
2002 that a substantial portion of the flammatory markers, C-reactive protein.
participants had prior health histories Orally administered estrogen prepara-
which included obesity, hyperlipidemia, tions have long been associated with an
26 NaturalNutmeg
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