What causes hot flushes? The neuroendocrine origin of vasomotor symptoms in the menopause

Vasomotor symptoms (VMS) such as hot flushes and night sweats are frequently encountered during menopause and can greatly reduce the quality of life. These symptoms are causally related to decreasing estradiol concentrations, mainly in the serum and subsequently also in the hypothalamic temperature regulating centre. The lack of estrogens alters neurotransmitter activity, especially in the serotonergic and noradrenergic pathways. Because sex steroids act as potent neuromodulators, the substitution of ovarian sex steroids by hormone replacement therapy is the most effective treatment option for VMS. When contraindications exist for the use of sex steroids, steroid-free drugs are a possible alternative. A better understanding of the physiology of thermoregulation, thermoregulatory dysfunction and adaptive processes of the brain may facilitate the development of new therapeutic approaches. Such drugs could then be used to treat vasomotor disorders even when the use of steroid hormones is contraindicated. This review article summarises our knowledge on the mechanisms of temperature regulation and describes deviations from this regulation during altered sex steroid conditions. Our current knowledge on neuroendocrinology of thermoregulation may serve as a basis for the use of steroid-free pharmacological intervention.