The aim of the present review is not to consider what neuroendocrine abnormalities occur in fibromyalgia per se, but rather to evaluate whether such abnormalities could explain the relationship between chronic stress and fibromyalgia. We have shown that activities of several endocrine axes and neurotransmitters change in parallel in both fibromyalgia and stress. In particular, there are decreased basal levels of growth hormone and IGF-I, androgens and oestrogens both in stress and fibromyalgia. Serotonin levels are reduced in both fibromyalgia and chronic stress, while levels of substance P are increased. Available evidence would favour diminished function of the HPA axis in fibromyalgia. The HPA axis is of course one of the major stress-response systems of the body and, in this respect, there seems to be divergence between fibromyalgia and stress. Nevertheless, similar changes in most other hormones and neurotransmitters would favour a role for stress in fibromyalgia.
There are large areas of uncertainty, however. For several hormones, the response to stress has been mainly studied in animals and there are very few reports on the response in humans. Even where human studies do exist, they may not be representative of the general population (e.g. military endurance exercises).
Also, for the present review, we are mainly interested in the effects of chronic psychological stress on various hormones and neurotransmitters, as this is more relevant for fibromyalgia than acute stress. It is, however, difficult to replicate conditions of chronic stress in experimental conditions. As a result, in many instances, the only data that could be found were from conditions mimicking acute stress.
Finally, an inherent difficulty with the study of hormones and neurotransmitters in both stress and fibromyalgia is to determine whether an effect is primary or secondary. All the studies discussed have been cross-sectional in nature, and do not allow conclusions on temporality. Thus, for example, low androgen levels in fibromyalgia could well be a result of chronic pain rather than the cause of it.
While the central theme of the present review is that chronic stress may lead to changes in various hormones and neurotransmitters, resulting in various manifestations of fibromyalgia such as pain and fatigue, it is not inconceivable that the chronic pain present in fibromyalgia can give rise to psychological stress, and thereby cause changes in neuroendocrine axes. Well-designed prospective studies are needed to resolve these issues.
To address this in relation to the HPA axis, our group is conducting a population study where we initially identified psychologically stressed subjects in the community through well-validated questionnaires. These subjects have had their HPA axis function assessed [102
] and are now being followed-up after a period of 15 months to help resolve the issue of whether derangements of the HPA axis in psychologically stressed subjects predict the future development of, as opposed to being a consequence of, chronic widespread pain.