Hormone replacement therapy and cardiovascular disease
Observational studies from the 1980s and 1990s showed that taking hormone replacement therapy (HRT) is protective against the development of coronary heart disease. From this data, HRT was prescribed for post-menopausal women to reduce symptoms of menopause and to prevent coronary heart disease, mainly in developed countries.
Over the late 1990s and early 2000s, several randomised clinical trials testing the use of HRT for a variety of outcomes (coronary heart disease, cancer, and stroke) were completed (Women’s Health Initiative, ESPRIT, WAVE, and so on). These data showed that there was no benefit of HRT for the prevention of coronary heart disease, and in fact for several outcomes, including stroke, HRT appears to increase risk.

Answer the question:
What are the possible explanations for the differences in findings from the observational studies and the randomised controlled trials examining HRT and cardiovascular disease?
Please answer this question with reference to the above example.
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