Most women who reach menopause will experience some symptoms. The hallmark of these are vasomotor symptoms (VMS) resulting from a narrowing of the thermoneutral zone and the sensation of heat, flushing and sweating. The most effective treatment for VMS is oestrogen therapy. However, oestrogen lack, per se, is not ultimate cause of the symptoms, neither is oestrogen the final mediator of therapeutic response. For those women who are reluctant or unable to take oestrogen-based therapies, remedies have either been to focus on physical factors, such as environmental cooling, or modulation of the presumed neurotransmitters, i.e. non-hormonal management.
Both norepinephrine and serotonin have been shown to alter thermoregulatory function in animal models, healthy volunteers and menopausal women. Norepinephrine has been proposed to mediate vasodilatation and a heat loss response. Clonidine has reduced VMS in some placebo-controlled trials. It is the only non-hormonal therapy approved by the TGA for this indication. Acute increases of serotonin in the synapse with SSRI lowers core body temperature but longterm excess of intrasynaptic serotonin may result in malignant hyperthermia. Low dose SSRIs have been used with modest effect for the management of VMS. Although its mechanism of action in reducing VMS is not fully elucidated, gabapentin is the available therapy which most closely approaches the efficacy of oestrogen.
Perhaps the most promising development is non-hormonal management is the research into the role of the KNDy neurons which have both reproductive and thermoregulatory function. Specifically, studies of neurokinin-B as the neurotransmitter involved in the hot flush have biological plausibility and randomised placebo-controlled studies of neurokinin-B receptor antagonism show that these new drugs closely approach the efficacy of oestrogen.