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(Drug information on 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, 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. 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. 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.