Hot flushes are one of the most bothersome symptoms affecting women in the peri-menopausal and post-menopausal period. Hot flushes can be defined as spontaneous sensations of warmth affecting the face, neck, and upper chest. Hot flushes may also be associated with anxiety, palpitations, and sweating. The intensity, duration, and frequency of hot flushes differ amongst women. Most women experience hot flushes during the first two years of the post-menopausal period. While some women may have minimal symptoms for one to two years, others experience symptoms that persist for several years.
Pathophysiology of Hot Flushes
The exact pathophysiology is unknown, but hot flushes are suspected to be linked to estrogen withdrawal, rather than the commonly thought cause of low estrogen levels. The body’s withdrawal process from estrogen is thought to cause central thermoregulatory centre dysfunction, culminating in hot flushes.
A relationship also exists between the onset of hot flushes and the release of luteinising hormone (LH). However, the evidence is conflicting as women with diminished or absent levels of LH still experience hot flushes. Other theories suggest that, in addition to estrogen withdrawal, other centrally acting mediators such as dopamine and serotonin may also be responsible for or linked to the development of hot flushes.
Hormone Replacement Therapy (HRT) is the gold standard and most effective treatment of hot flushes in women with menopause. HRT has been found to reduce the frequency of hot flushes by around 75%. However, for women with a contraindication or intolerance to HRT, non-hormonal treatment alternatives may be required.
Previous trials have examined the use of numerous non-hormonal agents to treat hot flushes including gabapentin, clonidine, methyldopa, and propranolol. The results of these trials found a reduction in the onset and severity of hot flushes. However, the side effect profile of these agents limits their use for the long-term treatment of hot flushes.
Many complementary medicines have also been used by patients for the treatment of hot flushes including black cohosh, ginseng, evening primrose oil, and motherwort, as well as acupuncture and other behavioural therapies. Results of these studies are conflicting and fail to demonstrate long-term safety data. Overall, clinical trials do not support the use of complementary and alternative medicines to treat hot flushes.
Several antidepressants including selective serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRIs) are primarily indicated for the treatment of depressive and anxiety disorders. They have also been identified as medications that may manage hot flushes in menopausal women. The way these antidepressants reduce hot flushes is not fully understood. It is known that decreased serotonin levels, possibly attributed to estrogen withdrawal, can be found in women with spontaneous or surgical menopause. Therefore, it has been suggested that serotonin may play a role in thermoregulation in mammals. Certain serotonin receptor subtypes are involved in thermoregulation. To put it simply, a low level of expression of these serotonin receptor subtypes can trigger an elevation in skin temperature and sweating which may contribute to hot flush symptoms. Therefore, using SSRIs or SNRIs to increase serotonin levels in menopausal women may assist in maintaining thermoregulation to decrease the frequency and severity of hot flushes.
Systematic reviews and meta-analysis studies have been conducted comparing the effect of SSRIs on menopausal hot flushes. Studies have found that the daily use of SSRIs is associated with a statistically significant decrease in the number of hot flushes per day over eight weeks. When used to alleviate hot flushes, the adverse side effects of SSRIs are usually minor including nausea, dry mouth, fatigue, tiredness, and decreased libido.
The low side effect profile coupled with the promising positive effects on hot flushes, allows SSRIs and SNRI antidepressants to be an acceptable option for treating menopausal women with hot flushes. These medications may be considered as an alternative in women who have a contraindication, intolerance, or aversion to HRT.
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