Abstract
The significant increase in cardiovascular disease risk with the loss of estrogen and progesterone at menopause has lead to increasing interest in the cardiovascular influences of female reproductive hormones. In addition to direct influences of estrogen to promote endothelium-dependent vasodilation, recent evidence demonstrates important influences of both estrogen and progesterone on the neural control of the peripheral circulation. These influences have been studied in two general contexts. First, the effects of these hormones on the sympathetic control of the cutaneous circulation have received substantial attention. The control of neurogenic vasodilation in the skin in response to hyperthermia is shifted to higher and lower internal temperatures by progesterone and estrogen, respectively. Reflex vasoconstrictor control of skin blood flow is shifted to higher internal temperatures when the hormones are elevated. Second, reproductive hormones have recently been shown to significantly alter sympathetic neural control of the skeletal muscle circulation. Sympathetic neural control of the skeletal muscle circulation (measured directly as muscle sympathetic nerve activity [MSNA]) is altered by hormone status such that resting MSNA is decreased by estrogen, as is the MSNA response to exercise. Furthermore, the baroreflex control of MSNA is significantly modified by estrogen and progesterone. Therefore, female reproductive hormones have widespread influences on the sympathetic control of the circulation in humans. The individual influences of estrogen and progesterone often antagonize one another, and when both hormone concentrations are increased, the net effect probably depends on their relative concentrations and bioactivity. The mechanisms responsible for these influences and their health-related implications deserve further attention.
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Herrington D. Role of estrogens, selective estrogen receptor modulators and phytoestrogens in cardiovascular protection.Can J Cardiol 2000; 16(Suppl E):5E-9E.
Farhat MY, Lavigne MC, Ramwell PW. The vascular protective effects of estrogen.FASEB J 1996; 10:615–624.
Sanada M, Higashi Y, Nakagawa K, Sasaki S, Kodama I, Sakashita T, Tsuda M, Ohama K. Oral estrogen replacement therapy increases forearm reactive hyperemia by increases in serum levels of nitric oxide in postmenopausal women.Gynecol Endocrinol 2001; 15:150–157.
Johnson JM, Proppe DW. Cardiovascular adjustments to heat stress. In:Handbook of Physiology. Environmental Physiology. Bethesda, MD: Am Physiol Soc; 1996. pp. 215–244.
Kellogg DL Jr, Pérgola PE, Piest KL, Kosiba WA, Crandall CG, Grossman M, Johnson JM. Cutaneous active vasodilation in humans is mediated by cholinergic nerve cotransmission.Circ Res 1995; 77:1222–1228.
Lewis T, Pickering GW. Vasodilation in the limbs in response to warming the body; with evidence for sympathetic vasodilator nerves in man.Heart 1931; 16:33–51.
Rowell LB. Cardiovascular adjustments to thermal stress. In:handbook of Physiology. The Cardiovascular System: Peripheral Circulation and Organ Blood Flow. Bethesda, MD: American Physiological Society; 1983. pp. 967–1023.
Kellogg DL Jr, Johnson JM, Kosiba WA. Baroreflex control of the cutaneous active vasodilator system in humans.Circ Res 1990; 66:1420–1426.
Brooks EM, Morgan AL, Pierzga JM, Wladkowski SL, O'Gorman JT, Derr JA, Kenney WL. Chronic hormone replacement therapy alters thermoregulatory and vasomotor function in postmenopausal women.J Appl Physiol 1997; 83:477–484.
Rothchild I, Barnes AC. The effects of dosage, and of estrogen, androgen or salicylate administration on the degree of body temperature elevation induced by progesterone.Endocrinology 1952; 50:485–496.
Stachenfeld NS, Silva C, Keefe DL. Estrogen modifies the temperature effects of progesterone.J Appl Physiol 2000; 88:1643–1649.
Stephenson LA, Kolka MA. Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women.J Appl Physiol 1999; 86:22–28.
Tankersley CG, Nicholas WC, Deaver DR, Mikita D, Kenney WL. Estrogen replacement in middle-aged women: thermoregulatory responses to exercise in the heat.J Appl Physiol 1992; 73:1238–1245.
Hessemer V, Brück K. Influence of menstrual cycle ons shivering, skin blood flow and sweating responses measured at night.J Appl Physiol 1985; 59:1902–1910.
Hessemer V, Brück K. Influence of menstrual cycle on thermoregulatory, metabolic and heart rate responses to exercise at night.J Appl Physiol 1985; 59:1911–1917.
Nakayama T, Suzuki M, Ishizuka N. Action of progesterone on preoptic thermosensitive neurones.Nature 1975; 258:80.
Silva NL, Boulant JA. Effects of testosterone, estradiol, and temperature on neurons in preoptic tissue slices.Am J Physiol 1986; 250:R625-R632.
Stephenson LA, Kolka MA. Menstrual cycle phase and time of day alter reference signal controlling arm blood flow and sweating.Am J Physiol 1985; 249 (Regulatory Integrative Comp Physiol 18):R186-R191.
Charkoudian N, Johnson JM. Modification of active cutaneous vasodilation by oral contraceptive hormones.J Appl Physiol 1997; 83:2012–2018.
Brooks-Asplund EM, Cannon JG, Kenney WL. Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women.Am J Physiol Regul Integr Comp Physiol 2000; 279:R839-R848.
Brooks-Asplund EM, Kenney WL. Chronic hormone replacement does not alter resting or maximal skin blood flow.J Appl Physiol 1998; 85:505–510.
Charkoudian N, Johnson JM. Altered reflex control of female reproductive hormones is independent of prostaglandins.Am J Physiol 1999; 276 (Heart Circ Physiol 45):H1634-H1640.
Charkoudian N, Johnson JM. Reflex control control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones.J Appl Physiol 1999; 87:381–385.
Rogers SM, Baker MA. Thermoregulation during exercise in women who are taking oral contraceptives.Eur J Appl Physiol Occup Physiol 1997; 75:34–38.
Sehic E, Székely M, Ungar AL, Oladehin A, Blatteis CM. Hypothalamic prostaglandin E2 during lipopolysacharide-induced fever in guinea pigs.Brain Res Bull 1996; 39:391–399.
Charkoudian N, Johnson JM. Female reproductive hormones and thermoregulatory control of skin blood flow.Exerc Sport Sci Rev 2000; 28:108–112.
Minson CT, Halliwill JR, Young TM, Joyner MJ. Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women.Circulation 2000; 101:862–868.
Ettinger SM, Silber DH, Gray KS, Smith MB, Yang QX, Kunselman AR, Sinoway LI, Effects of the ovarian cycle on sympathetic neural outflow during static exercise.J Appl Physiol 1998; 85:2075–2081.
Minson CT, Halliwill JR, Young TM, Joyner MJ. Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives.Circulation 2000; 102:1473–1476.
He XR, Wang W, Crofton JT, Share L. Effects of 17beta-estradiol on sympathetic activity and pressor response to phenylephrine in ovariectomized rats.Am J Physiol 1998; 275:R1202-R1208.
Heesch CM, Rogers RC. Effects of pregnancy and progresterone metabolites on regulation of sympathetic outflow.Clin Exp Pharmacol Physiol 1995; 22:136–142.
Sundlöf G, Wallin BG. The variability of muscle sympathetic nerve activity in resting recumbent man.J Physiol (London) 1977; 272:383–397.
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Financial support for the author's work was provided by National Institutes of Health grants HL59166, NRSA AR/HL 0860-01, and HL 63328.
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Charkoudian, N. Influences of female reproductive hormones on sympathetic control of the circulation in humans. Clinical Autonomic Research 11, 295–301 (2001). https://doi.org/10.1007/BF02332974
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DOI: https://doi.org/10.1007/BF02332974