The menopause transition.

New paradigms for the study of menopause will increase our understanding of whether symptoms, syndromes, and chronic diseases are associated with menopause. Rather than considering menopause as a discrete event, it has become clear that the menopause transition takes place over many years. Although this realization is central to our understanding of menopause, it is difficult to measure the temporal pattern of changes in hormones and their relation to concurrent or subsequent health-related events. The model of hormonal changes at the time of the transition has been expanded to include not only declines in estrogen but changes in a broader range of hormones, including the potential role of androgens. New models are attempting to account for the pattern and frequency of changes in hormone levels. Another level of complexity is contributed by the expansion of the menopause model to include comorbid medical and psychiatric conditions, environmental influences, and behaviors as covariates that influence the expression of menopause-related events. Although this more complicated paradigm makes the conduct of menopause research more challenging, it is also likely to elucidate previously confusing data, as the proper understanding of potentially complex exposures, effect modifiers, and confounders is more likely to provide clearer answers to critical research questions.