Center for Psychobiological and Psychosomatic Research University of Trier Trier D-54286, Germany
In a recent study, Komesaroff et al. (1) reported the effects of an 8-week estrogen treatment on endocrine responses to mental stress in perimenopausal women. Among other effects, they reported reduced ACTH and cortisol responses after estrogen treatment. Although the data seem to support findings of reduced hypothalamus-pituitary-adrenal (HPA) stress responses to mental stress in premenopausal women compared to men (2), the present results are difficult to interpret.
We know that the HPA response to mental stress is profoundly influenced by novelty, predictability, controllability, and anticipation of the stressful situation (3). As we (4, 5) and other laboratories (6) have shown, HPA responses significantly decrease when subjects are exposed to the same stress or repeatedly. The response decrement reflects psychological processes including coping, appraisal of the situation and others. The reported effects of lower HPA responses to the second stress test in the estrogen-treated subjects are, therefore, significantly confounded with habituation to the repeated stress tests. Furthermore, habituation to repeated psychological stress seems to be a function of personality traits like low self-esteem and neuroticism (4). Unfortunately, no information on subjective responses or personality traits have been provided.
A second problem with the study protocol is the timing of blood samples. Thirty minutes after brachial cannulation, a "baseline" blood sample was obtained by Komesaroff et al. (1) However, this measure can hardly serve as a baseline because there is ample evidence for significant endocrine responses to catheterization with large individual differences (e.g. Refs. 7, 8). With only five or seven subjects in each group (as in the present study), it takes only one or two subjects responding to the stress of catheterization to obtain elevated baseline levels 30 min later. This is most evident in the norepinephrine, epinephrine, and ACTH levels in the estrogen group before treatment. Basal levels differed as much as 200% and more between the two groups on the first stress test, which in turn can have a profound effect on the endocrine responsiveness, and a comparison of the endocrine responses to the two stress exposures. It, therefore, remains an open question whether or not estradiol treatment will alter the endocrine stress response in postmenopausal women. In light of the wide-spread use of estrogen replacement therapy, this is an important research area that requires more detailed investigations. It is to be hoped that in future studies the psychology behind endocrine responses will be carefully considered when mental stress is investigated.
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