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Current Management of Menopausal Symptoms in Cancer Patients

Current Management of Menopausal Symptoms in Cancer Patients

Barton, Loprinzi, and Gostout provide a comprehensive,
accurate, and multidisciplinary review of the management of menopausal symptoms
in patients with a previous diagnosis of cancer. The article is clearly enhanced
by the authorship of individuals from different backgrounds, each of whom bring
a valuable perspective to the subject. Additional attention to several issues
would, however, make interpretation of the data on this subject, and hence, the
management of patients with these problems, more clear.

Observational vs Randomized Trial Data

First, it is important to distinguish between data obtained from
observational trials and data obtained from randomized intervention trials. The
authors discuss the results of both types of trials with little differentiation.
They are not, of course, the first or the only to mix these levels of evidence
with insufficient distinction. They do point out, however, that the few
randomized trials of estrogen replacement therapy (ERT) for coronary artery
disease produced results that were quite different from those obtained from a
long series of observational studies.

Observational data have repeatedly shown an association between the use of
estrogen replacement therapy (ERT) or estrogen and progesterone replacement
therapy (hormone replacement therapy, or HRT) and a reduced incidence of
myocardial infarction and/or death from cardiac disease. This phenomenon was
believed to be explicable by documented changes in levels of low-density
lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol in women
receiving estrogen therapy, and perhaps by other beneficial effects on vessels,
platelets, and myocardium.

At least one trial of secondary prevention following one cardiac event,[1]
however, has shown that women randomized to receive ERT actually experience an
increased number of cardiac events in the first year following randomization
(although they may experience fewer subsequent events, such that these effects
may balance out over 3 to 4 years). In addition, an overview analysis of cardiac
end points in randomized trials of HRT with other primary end points has shown
no significant reduction in cardiac events.[2] Patients in such studies are
being followed further to ascertain their ultimate outcome. Similar results have
been seen with the use of estrogen as primary prevention in the Women’s Health
Initiative.[3] In that trial, women randomized to receive ERT or HRT experienced
an increased number of cardiac events in the first 18 months to 2 years but then
experienced fewer subsequent events.

Treatment Standards Overturned

The contradictory data in this field are a frightening demonstration of the
way in which the dogma of many years, based on observational studies, can be
overturned by trials of stronger methodologic design. It has previously been
well appreciated that women who use ERT/HRT assume much different health-seeking
behaviors than women who do not. Women who use ERT/HRT are known to see
physicians more frequently, have more gynecologic exams and Pap smears, be more
likely to exercise, weigh less, and pursue different diets. Thus, the
association between ERT/HRT and reduced cardiac events may not be a
cause-and-effect issue.


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