Hot flushes, vascular reactivity and the role of the α-adrenergic system

ABSTRACT

Background Seventy percent of postmenopausal women suffer from hot flushes but the pathophysiology is poorly understood. Proposed mechanisms include altered peripheral vascular reactivity and a narrowed thermoneutral zone. A trigger has not yet been identified; however, the α-adrenergic system, and specifically noradrenaline, has been implicated.

Aim To assess the role of the α-adrenergic system by studying the effect of clonidine (α-adrenergic agonist) on flushes and cutaneous microvascular perfusion.

Methods Thirty-two postmenopausal women with severe flushing and 14 non-flushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine (ACh – endothelium-dependent) and sodium nitroprusside (SNP – endothelium-independent). In a double-blind, longitudinal, cross-over study, clonidine (an α-adrenergic agonist) was compared to placebo in its ability to modulate this response in the flushing group of women.

Results The response of the subcutaneous vessels was greater in women who flushed than those who did not (ACh, p < 0.001 and SNP, p = 0.001). However, even though the intensity and number of flushes were decreased by clonidine, there was no difference compared to placebo (p = 0.21) and this ‘placebo effect’ was also noted in perfusion responses (ACh, p = 0.98; SNP, p = 0.50).

Conclusion There was a significant ‘placebo effect’ for both clinical response and the reactivity of the subcutaneous vessels, making conclusions regarding the role of the α-adrenergic nervous system in hot flushing difficult to determine at a peripheral level. The mechanism for the change in vascular reactivity remains unclear.

Key words::

• HOT FLUSHES
• ALPHA-ADRENERGIC SYSTEM
• VASCULAR FUNCTION

Conflict of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Source of funding This work has been funded by The Translational Medicine Research Collaboration and Wellbeing of Women.