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The hot flush: symptom of menopause or sign of disease?

Knowledge of post-reproductive life dates to ancient Egypt and Greece; however, an understanding of what caused it, its consequences and how to treat them were not formed until the 20th century advances in endocrinology. Menopause is still a retrospective diagnosis, defined as the permanent absence of menstruation after more than 12 months' amenorrhea, but, for many women, it is the onset of hot flushes (or hot flashes) and other symptoms that herald the beginning of ‘the change’. In this issue of Climacteric, Sturdee and colleagues provide a comprehensive review of the hot flush including physical and cognitive aspects, physiological changes and associated pathophysiology. Vasomotor symptoms (VMS), including the hot flush, are amongst the commonest symptoms of the menopause transition. The prevalence of hot flushes varies between countries, between regions and between women. For individual women, the bother caused by a hot flush depends on many external factors including cultural attitudes, family and social networks, general health and well-being, social status and a societal understanding of the menopause. Hot flushes are a heat dissipation response characterized by flushing and sweating, probably triggered by a narrowing of the thermoneutral zone in the hypothalamus and an increased central secretion of noradrenaline. The neuroendocrine changes associated with a hot flush may have significance far beyond the immediate distress and discomfort experienced at the time. Treatments for hot flushes are innumerable. Almost every imaginable extract of human or animal tissue has been tried as well as alcohol, herbs and grains, phytoestrogens, acupuncture and heavy metals including lead, mostly with limited benefit and sometimes with harm. Hot flushes subside with time, although not as quickly as we once thought, and the placebo response in randomized, clinical trials is generally high, requiring any active comparator to have a high rate of response to demonstrate statistically significant benefit. To date, the most effective treatment for VMS has been estrogen replacement therapy, combined with progestogen when endometrial protection is required. Now, new nonhormonal options are under investigation including modulation of transmission via the kisspeptin–neurokinin B–dynorphin signaling system with neurokinin B receptor antagonists. These compounds, or others like them, may at last provide an effective alternative for women unable or unwilling to use hormonal interventions to alleviate their symptoms. The hot flush may have more serious connotations. A review article by Biglia and colleagues raises the question of whether vasomotor symptoms are a marker of chronic disease, by pointing to a growing body of evidence linking hot flushes to a range of chronic postmenopausal conditions including cardiovascular disease, osteoporosis and cognitive decline. A longitudinal study of over 11 000 women followed for 14 years reported an increased risk of coronary heart disease for women with hot flushes or night sweats which persisted after correction for other risk factors. Possible mechanisms to explain this include reports linking vasomotor symptoms with adverse lipid profiles, a rise in systolic blood pressure, increased insulin resistance and inflammatory markers. Results from the Study of Women Across the Nation, a multiethnic US study, have linked a higher frequency of hot flushes with both a rise in blood pressure and, in younger women, a worsening of endothelial function. Similar links are seen between hot flushes and other diseases of aging. For example, US researchers found that lower bone density and a higher rate of bone turnover during the menopause transition were linked to the presence of vasomotor symptoms. Australian researchers found moderate to severe vasomotor symptoms were associated with moderate to severe depressive symptoms. Perhaps then, vasomotor symptoms, the classical symptom of the menopause, should also be regarded as a warning of other chronic disease. The midlife women’s health check is an opportunity for a discussion of healthy lifestyle measures such as regular exercise, normalization of weight, cessation of smoking and a healthy diet. It should also be a time for a thorough general health check and for appropriate screening tests to minimize the risk of diseases of aging. Should we also seek out the troublesome hot flush and, if found, institute primary prevention? Should that be hormonal or is there another option? Too often this question has been ignored because of concerns regarding inappropriate use of menopausal hormone therapy (MHT). Early observational studies suggested long-term health benefits for users of MHT but the Women’s Health Initiative (WHI) randomized, clinical trial initially found the opposite. Subsequent re-analysis of WHI data with age stratification, newer randomized, clinical trials, observational studies and meta-analyses have