The menopausal hot flush--anything new?

Although the hot flush is generally recognised by women and the medical profession as the most characteristic and often a very distressing symptom of the climacteric, it remains an enigma. The physiological changes associated with the hot flush are different from any other flushing condition, with an increased peripheral blood flow, increased heart rate and in particular a decrease in galvanic skin resistance, which is unique to the flush. Flushing occurs as a result of disturbance of the temperature regulating mechanism situated in the hypothalamus, and probably a reduction in the thermoneutral zone, within which fluctuations of basal body temperature do not provoke compensatory vascular responses. Many factors have been implicated, including hormone releasing factors, gonadotrophins and neurohumorals. However, the role of oestrogen is critical and the clinical value of oestrogen therapy is well established and has been confirmed by a Cochrane review. Nevertheless, the precise mechanism by which reduced circulating levels of oestrogen are involved in causing the flush has not yet been established. Priming with oestrogen seems to be an essential pre-requisite for flushing, as young women with ovarian dysgenesis and very low circulating levels of oestrogen never have hot flushes unless they are given oestrogen replacement therapy, which is later discontinued. Oestrogen antagonist activity by selective oestrogen receptor modulators such as tamoxifen and raloxifene can also cause flushing. A link with gonadotrophins is demonstrated by a temporal association of flushes with the pulsatile release of luteinising hormone (LH). However, if LH pulses are eliminated by GnRH analogue, the frequency of flushing is not altered, which confirms that LH is merely associated with the flush rather than being causative. It is probable that the flush is initiated by a supra-pituitary mechanism which is influenced by the hypothalamic factors responsible for pulsatile LH release. A variety of chemical pathways have been proposed involving serotonin, noradrenalin and dopamine. Trials of drugs that selectively inhibit the re-uptake of serotonin and noradrenalin have shown some beneficial effects, as also has gabapentin, but often the results have been disappointing, and certainly less than the response seen with oestrogen or tibolone. The prevalence of hot flushes varies considerably around the world and is less in the Far East than in the west. Differences in diet and in particular the intake of phytoestrogens has been implicated and many studies have tried to establish whether dietary supplementation with phytoestrogens might be a suitable alternative to conventional hormone replacement therapy (HRT). So far, the results are disappointing. Other lifestyle measures such as avoiding alcohol, caffeine and spicy foods, keeping the core body temperature cool, paced respiration, taking exercise and even acupuncture may help. Hot flushes remain a major cause of reduced quality of life in a large proportion of menopausal women, but perhaps because they are not fatal and are usually self-limiting, there has been rather limited research or clinical interest. However, for the increasing number of women being treated with tamoxifen for breast cancer, and for whom oestrogen will usually be contra-indicated or unsuitable, there is an urgent need to identify the underlying mechanism so that appropriate, specific and safe non-oestrogen therapy can be offered to improve their quality of life.