How do female reproductive hormones influence vascular control in the hand

Evidence is emerging that female reproductive hormones exert important non-reproductive influences on cardiovascular control, including the control of the skin circulation in young and older women. Estrogen and progesterone have been shown to influence reflex sympathetically mediated vasodilation and vasoconstriction as well as local vascular control of the skin in humans [1, 2]. In this issue of Clinical Autonomic Research, Cankar and Finderle report that women exhibit greater cutaneous vasoconstriction in response to cooling of the hand compared to men. These investigators measured cutaneous vasoconstrictor responses on the ventral aspect of the index finger of a hand being directly cooled to 15 °C. They also measured the vasoconstrictor response on the contralateral hand as an index of reflex sympathetically mediated vasoconstriction. Both the direct (local) and reflex components of the response were augmented in women compared to men. Furthermore, the direct vasoconstrictor response to hand cooling varied over the menstrual cycle. Vasoconstriction was greater in the luteal phase (when estrogen and progesterone are elevated) compared to the early follicular phase (when both hormones are low). Taken together, the results of their study suggest that female reproductive hormones act to augment vasoconstrictor responses to cooling in the hand. This is in contrast to previous results in the forearm, where cutaneous vasoconstriction to local cooling was not affected by reproductive hormone status [3]. The differences in results in the hand and forearm may be accounted for by the much higher baseline blood flow in the hand (which would allow detection of small differences in vasoconstrictor responses not detectable in the forearm), or differences in control mechanisms in the glabrous skin of the hand compared to the non-glabrous skin of the forearm [7]. The cutaneous vascular response to local cooling is complex, and includes local activation of sympathetic vasoconstrictor nerves, independent of central neural control [8], and increased post-synaptic alpha-adrenergic responsiveness [4, 9]. A potential explanation for the findings of Cankar and Finderle is evidence that alphaadrenergic vasoconstriction in women may be augmented in the luteal phase of the menstrual cycle compared to the early follicular phase [6]. The findings of Cankar and Finderle highlight the need for further mechanistic research in this important area. Which of the several mechanisms involved in the cutaneous vasoconstrictor response to local cooling is/are altered by reproductive hormone status? What are the implications of these findings for patients with Raynaud’s phenomenon? The higher prevalence of primary Raynaud’s in women, and the association of estrogen replacement therapy with increased risk for Raynaud’s [5] suggest that reproductive hormones contribute. However, specific mechanisms for their role in this disorder remain to be elucidated. Finally, studies like the one from Cankar and Finderle reemphasize the importance of integrative approaches to the study of physiology in an era of increasing focus on “reductionist” methodology. Identification of molecular, genomic and proteomic mechanisms, while important and exciting, must be assessed in an integrative context in order to have true meaning in the advancement of human physiology and, ultimately, of our ability to understand and treat disease.