Relief of vasomotor symptoms: with NK3R antagonists or with MHT?

Jean Michel Foidart kicked off our early morning session on Day 3 sharing a potentially novel way to relieve vasomotor symptoms (VMS). This has been a popular topic at ESG so far and was also covered yesterday in the Gynecology: AUB, Prolapse and Menopause.

VMS symptoms have been causing problems in peri and post-menopausal women for a number of years and is the main reason women seek treatment. Estrogens are the most effective treatment for VMS but concerns persist around the risks associated. As a result other ways of reducing hot flushes are being investigated.

The anterior hypothalamic nucleus is the control site of the central heating system of the body. In the hypothalamus, KNDy neurons are present and act as a potential trigger of hot flushes. KNDy neurons respond to circulating estrogens, when these hormones are at a very low level, as is the case during menopause, these neurons become very active; they grow very large and become several times larger than they are when estrogen is present. This increased signalling activity triggers heat loss mechanisms like sweating and vasodilation.  It has been found that antagonists of NK3R signalling, can stop KNDy neuron hyperactivity, thereby restoring normal functioning of heat dissipation effectors and resolving the dysregulation that results in VMS.  A number of NK3R antagonists are in phase II clinical trials and being investigated, phase III data will be required to determine if this is an applicable alternative to MHT for treatment of VMS.

But do we need an alternative to MHT?

Whilst the use of MHT has been vigorously debated, earlier observational data showed many benefits including reduced risk of coronary heart disease and mortality. Reassessment of clinical trials in women initiating treatment close to the onset of menopause and newer studies and meta-analyses now show demonstrated benefits and rare risks. In addition the effects of reduced CHD and mortality in women initiating therapy around menopause suggest a possible role for MHT in primary prevention. Futher benefits in reducing menopausal symptoms, osteoporosis prevention, prevention of new onset diabetes mellitus and improved quality of life all make a compelling argument for the use of MHT for prevention and not only the treatment of moderate to severe hot flushes.

NK3 receptor antagonists don’t convey these added benefits of prevention of osteoporosis, maintenance of cognitive function, reduce CVD risk or impact on benefits of insulin production and as a result Jean believes should be reserved for the 5% of women where MHT is contra-indicated.