Vascular aging, featuring endothelial dysfunction and large artery stiffening, is a major risk factor for developing cardiovascular disease (CVD). In women, vascular aging appears to be accelerated during the menopause transition, particularly around the late perimenopausal period, presumably related to declines in ovarian function and estrogen levels. The mechanisms underlying endothelial dysfunction and large artery stiffening with the menopause transition are not completely understood. Oxidative stress and the proinflammatory cytokine tumor necrosis factor-α contribute to endothelial dysfunction and large artery stiffening in estrogen-deficient postmenopausal women. Habitual endurance exercise attenuates the age-related increase in large artery stiffness in estrogen-deficient postmenopausal women and can reverse arterial stiffening to premenopausal levels in estrogen-replete postmenopausal women. In contrast, estrogen status appears to play a key permissive role in the adaptive response of the endothelium to habitual endurance exercise in that endothelial improvements are absent in estrogen-deficient women but present in estrogen-replete women. We review here the current state of knowledge on the biological defects underlying vascular aging across the menopause transition, with particular focus on potential mechanisms, the role of habitual exercise in preserving vascular health, and key areas for future research. 1. Introduction Despite significant declines in cardiovascular disease (CVD) mortality, CVD is still the leading cause of death in adults . Vascular aging, featuring endothelial dysfunction and large artery stiffening, is a major risk factor for the development of CVD, in that it combines with other known risk factors to create an age-disease interaction . In women, vascular aging is unique in that adverse changes in CVD risk factors (e.g., blood pressure, lipids, and adiposity) occur during a time of profound changes in the hormonal environment as women transition through menopause. The acceleration of age-associated declines in vascular function in women after menopause suggests that menopause may be a triggering event that leads to increased vascular vulnerability as women age. Thus, understanding the underlying biological defects associated with vascular aging across the menopause transition is important for the development of strategies to maintain vascular health and decrease CVD mortality. This review will focus on some of the work that we have done on the modulatory influence of sex hormone deficiency on vascular aging in
E. G. Lakatta and D. Levy, “Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease,” Circulation, vol. 107, no. 1, pp. 139–146, 2003.
K. L. Moreau, K. L. Hildreth, A. L. Meditz, K. D. Deane, and W. M. Kohrt, “Endothelial function is impaired across the stages of the menopause transition in healthy women,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 12, pp. 4692–4700, 2012.
K. M. Gavin, D. R. Seals, A. E. Silver, and K. L. Moreau, “Vascular endothelial estrogen receptor α is modulated by estrogen status and related to endothelial function and endothelial nitric oxide synthase in healthy women,” The Journal of Clinical Endocrinology & Metabolism, vol. 94, no. 9, pp. 3513–3520, 2009.
K. L. Moreau, A. Meditz, K. D. Deane, and W. M. Kohrt, “Tetrahydrobiopterin improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women,” The American journal of physiology: Heart and circulatory physiology, vol. 302, no. 5, pp. H1211–1218, 2012.
K. L. Hildreth, W. M. Kohrt, and K. L. Moreau, “Oxidative stress contributes to large elastic arterial stiffening across the stages of the menopausal transition,” Menopause, vol. 21, no. 6, pp. 624–632, 2014.
K. L. Moreau, A. J. Donato, D. R. Seals et al., “Arterial intima-media thickness: Site-specific associations with HRT and habitual exercise,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 283, no. 4, pp. H1409–H1417, 2002.
K. L. Moreau, A. J. Donato, D. R. Seals, C. A. DeSouza, and H. Tanaka, “Regular exercise, hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women,” Cardiovascular Research, vol. 57, no. 3, pp. 861–868, 2003.
K. L. Moreau, B. L. Stauffer, W. M. Kohrt, and D. R. Seals, “Essential role of estrogen for improvements in vascular endothelial function with endurance exercise in postmenopausal women,” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 1, pp. 4507–4515, 2013.
R. Rossi, A. Nuzzo, G. Origliani, and M. G. Modena, “Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women,” Journal of the American College of Cardiology, vol. 51, no. 10, pp. 997–1002, 2008.
D. S. Celermajer, K. E. Sorensen, D. J. Spiegelhalter, D. Georgakopoulos, J. Robinson, and J. E. Deanfield, “Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women,” Journal of the American College of Cardiology, vol. 24, no. 2, pp. 471–476, 1994.
K. L. Moreau, K. D. Deane, A. L. Meditz, and W. M. Kohrt, “Tumor necrosis factor-a inhibition improves endothelial function and decreases arterial stiffness in estrogen-deficient postmenopausal women,” Atherosclerosis, vol. 230, pp. 390–396, 2013.
A. Sherwood, J. K. Bower, J. McFetridge-Durdle, J. A. Blumenthal, L. K. Newby, and A. L. Hinderliter, “Age moderates the short-term effects of transdermal 17β-estradiol on endothelium-dependent vascular function in postmenopausal women,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 8, pp. 1782–1787, 2007.
C. Vitale, G. Mercuro, E. Cerquetani et al., “Time since menopause influences the acute and chronic effect of estrogens on endothelial function,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 2, pp. 348–352, 2008.
P. J. M. Best, P. B. Berger, V. M. Miller, and A. Lerman, “The effect of estrogen replacement therapy on plasma nitric oxide and endothelin-1 levels in postmenopausal women,” Annals of Internal Medicine, vol. 128, no. 4, pp. 285–288, 1998.
H. Kawano, T. Motoyama, K. Kugiyama et al., “Gender difference in improvement of endothelium-dependent vasodilation after estrogen supplementation,” Journal of the American College of Cardiology, vol. 30, no. 4, pp. 914–919, 1997.
E. H. Lieberman, M. D. Gerhard, A. Uehata et al., “Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women,” Annals of Internal Medicine, vol. 121, no. 12, pp. 936–941, 1994.
E. Tan, M. V. Gurjar, R. V. Sharma, and R. C. Bhalla, “Estrogen receptor-α gene transfer into bovine aortic endothelial cells induces eNOS gene expression and inhibits cell migration,” Cardiovascular Research, vol. 43, no. 3, pp. 788–797, 1999.
G. M. Rubanyi, A. D. Freay, K. Kauser et al., “Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta: gender difference and effect of estrogen receptor gene disruption,” Journal of Clinical Investigation, vol. 99, no. 10, pp. 2429–2437, 1997.
C. Pinna, A. Cignarella, P. Sanvito, V. Pelosi, and C. Bolego, “Prolonged ovarian hormone deprivation impairs the protective vascular actions of estrogen receptor alpha agonists,” Hypertension, vol. 51, no. 4, pp. 1210–1217, 2008.
J. J. Pinzone, H. Stevenson, J. S. Strobl, and P. E. Berg, “Molecular and cellular determinants of estrogen receptor α expression,” Molecular and Cellular Biology, vol. 24, no. 11, pp. 4605–4612, 2004.
J. F. Keaney Jr., G. T. Shwaery, A. Xu et al., “17β-Estradiol preserves endothelial vasodilator function and limits low- density lipoprotein oxidation in hypercholesterolemic swine,” Circulation, vol. 89, no. 5, pp. 2251–2259, 1994.
I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals, “Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing,” The Journal of Physiology, vol. 556, part 1, pp. 315–324, 2004.
G. Kojda and D. Harrison, “Interactions between NO and reactive oxygen species: pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure,” Cardiovascular Research, vol. 43, no. 3, pp. 562–571, 1999.
K. K. Lam, Y. M. Lee, G. Hsiao, S. Y. Chen, and M. H. Yen, “Estrogen therapy replenishes vascular tetrahydrobiopterin and reduces oxidative stress in ovariectomized rats,” Menopause, vol. 13, no. 2, pp. 294–302, 2006.
A. Virdis, L. Ghiadoni, S. Pinto et al., “Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women,” Circulation, vol. 101, no. 19, pp. 2258–2263, 2000.
N. J. Alp and K. M. Channon, “Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 3, pp. 413–420, 2004.
M. J. Crabtree, A. L. Tatham, A. B. Hale, N. J. Alp, and K. M. Channon, “Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways,” Journal of Biological Chemistry, vol. 284, no. 41, pp. 28128–28136, 2009.
I. A. Arenas, S. J. Armstrong, Y. Xu, and S. T. Davidge, “Chronic tumor necrosis factor-α inhibition enhances NO modulation of vascular function in estrogen-deficient rats,” Hypertension, vol. 46, no. 1, pp. 76–81, 2005.
A. Csiszar, N. Labinskyy, K. Smith, A. Rivera, Z. Orosz, and Z. Ungvari, “Vasculoprotective effects of anti-tumor necrosis factor- treatment in aging,” The American Journal of Pathology, vol. 170, no. 1, pp. 388–398, 2007.
B. R. Clapp, A. D. Hingorani, R. K. Kharbanda et al., “Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress,” Cardiovascular Research, vol. 64, no. 1, pp. 172–178, 2004.
J. Pleiner, F. Mittermayer, G. Schaller, C. Marsik, R. J. MacAllister, and M. Wolzt, “Inflammation-induced vasoconstrictor hyporeactivity is caused by oxidative stress,” Journal of the American College of Cardiology, vol. 42, no. 9, pp. 1656–1662, 2003.
M. Yoshizumi, M. A. Perrella, J. C. Burnett Jr., and M.-E. Lee, “Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life,” Circulation Research, vol. 73, no. 1, pp. 205–209, 1993.
F. Mittermayer, J. Pleiner, G. Schaller et al., “Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial dysfunction,” The American Journal of Physiology: Heart and Circulatory Physiology, vol. 289, no. 4, pp. H1752–H1757, 2005.
M. Abu-Taha, C. Rius, C. Hermenegildo et al., “Menopause and ovariectomy cause a low grade of systemic inflammation that may be prevented by chronic treatment with low doses of estrogen or losartan,” Journal of Immunology, vol. 183, no. 2, pp. 1393–1402, 2009.
H. Bismar, I. Diel, R. Ziegler, and J. Pfeilschifter, “Increased cytokine secretion by human bone marrow cells after menopause or discontinuation of estrogen replacement,” The Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 11, pp. 3351–3355, 1995.
S. Vehkavaara, A. Silveira, T. Hakala-Ala-Pietil？ et al., “Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women,” Thrombosis and Haemostasis, vol. 85, no. 4, pp. 619–625, 2001.
L. Sunday, M. M. Tran, D. N. Krause, and S. P. Duckles, “Estrogen and progestagens differentially modulate vascular proinflammatory factors,” The American Journal of Physiology: Endocrinology and Metabolism, vol. 291, no. 2, pp. E261–E267, 2006.
H. Sumino, S. Ichikawa, S. Kasama et al., “Different effects of oral conjugated estrogen and transdermal estradiol on arterial stiffness and vascular inflammatory markers in postmenopausal women,” Atherosclerosis, vol. 189, no. 2, pp. 436–442, 2006.
D. Xing, W. Feng, A. P. Miller et al., “Estrogen modulates TNF-α-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-β activation,” The American Journal of Physiology: Heart and Circulatory Physiology, vol. 292, no. 6, pp. H2607–H2612, 2007.
N. G. Majmudar, S. C. Robson, and G. A. Ford, “Effects of the menopause, gender, and estrogen replacement therapy on vascular nitric oxide activity,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 4, pp. 1577–1583, 2000.
H. Smulyan, R. G. Asmar, A. Rudnicki, G. M. London, and M. E. Safar, “Comparative effects of aging in men and women on the properties of the arterial tree,” Journal of the American College of Cardiology, vol. 37, pp. 1374–1380, 2001.
Y. Nagai, C. J. Earley, M. K. Kemper, C. S. Bacal, and E. J. Metter, “Influence of age and postmenopausal estrogen replacement therapy on 1 carotid arterial stiffness in women,” Cardiovascular Research, vol. 41, no. 1, pp. 307–311, 1999.
I. C. D. Westendorp, M. L. Bots, D. E. Grobbee et al., “Menopausal status and distensibility of the common carotid artery,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 3, pp. 713–717, 1999.
C. Rajkumar, B. A. Kingwell, J. D. Cameron et al., “Hormonal therapy increases arterial compliance in postmenopausal women,” Journal of the American College of Cardiology, vol. 30, no. 2, pp. 350–356, 1997.
A. Scuteri, E. G. Lakatta, A. J. G. Bos, and J. L. Fleg, “Effect of estrogen and progestin replacement on arterial stiffness indices in postmenopausal women,” Aging—Clinical and Experimental Research, vol. 13, no. 2, pp. 122–130, 2001.
Y. L. Liang, H. Teede, and L. M. Shiell, “Effects of oestrogen and progesterone on age-related changes in arteries of postmenopausal women,” Clinical and Experimental Pharmacology and Physiology, vol. 24, no. 6, pp. 457–459, 1997.
A. K. Natoli, T. L. Medley, A. A. Ahimastos et al., “Sex steroids modulate human aortic smooth muscle cell matrix protein deposition and matrix metalloproteinase expression,” Hypertension, vol. 46, no. 5, pp. 1129–1134, 2005.
W. A. Riley, G. W. Evans, A. R. Sharrett, G. L. Burke, and R. W. Barnes, “Variation of common carotid artery elasticity with intimal-medial thickness: the ARIC study,” Ultrasound in Medicine and Biology, vol. 23, no. 2, pp. 157–164, 1997.
R. K. Dubey, E. K. Jackson, D. G. Gillespie, L. C. Zacharia, B. Imthurn, and P. J. Keller, “Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 4, pp. 964–972, 2000.
M. Matsuda, T. Nosaka, M. Sato, and N. Ohshima, “Effects of physical exercise on the elasticity and elastic components of the rat aorta,” European Journal of Applied Physiology and Occupational Physiology, vol. 66, no. 2, pp. 122–126, 1993.
B. K. Yoon, W. K. Oh, B. Kessel et al., “17 -estradiol inhibits proliferation of cultured vascular smooth muscle cells induced by lysophosphatidylcholine via a nongenomic antioxidant mechanism,” Menopause, vol. 8, no. 1, pp. 58–64, 2001.
R. K. Dubey, D. G. Gillespie, L. C. Zacharia et al., “Methoxyestradiols mediate the antimitogenic effects of estradiol on vascular smooth muscle cells via estrogen receptor-independent mechanisms,” Biochemical and Biophysical Research Communications, vol. 278, no. 1, pp. 27–33, 2000.
M. A. Espeland, W. Applegate, C. D. Furberg, D. Lefkowitz, L. Rice, and D. Hunninghake, “Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women,” The American Journal of Epidemiology, vol. 142, no. 10, pp. 1011–1019, 1995.
B. P. McGrath, Y. Liang, H. Teede, L. M. Shiel, J. D. Cameron, and A. Dart, “Age-related deterioration in arterial structure and function in postmenopausal women: Impact of hormone replacement therapy,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 7, pp. 1149–1156, 1998.
F. A. Tremollieres, F. Cigagna, C. Alquier, C. Cauneille, J. Pouilles, and C. Ribot, “Effect of hormone replacement therapy on age-related increase in carotid artery intima-media thickness in postmenopausal women,” Atherosclerosis, vol. 153, no. 1, pp. 81–88, 2000.
I. C. D. Westendorp, B. A. In't Veld, M. L. Bots et al., “Hormone replacement therapy and intima-media thickness of the common carotid artery: the Rotterdam study,” Stroke, vol. 30, no. 12, pp. 2562–2567, 1999.
I. B. Wilkinson, A. Qasem, C. M. McEniery, D. J. Webb, A. P. Avolio, and J. R. Cockcroft, “Nitric oxide regulates local arterial distensibility in vivo,” Circulation, vol. 105, no. 2, pp. 213–217, 2002.
R. P. Wildman, A. B. Colvin, L. H. Powell et al., “Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN),” Menopause, vol. 15, no. 3, pp. 414–421, 2008.
K. A. Matthews, L. H. Kuller, K. Sutton-Tyrrell, and Y. Chang, “Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women,” Stroke, vol. 32, no. 5, pp. 1104–1110, 2001.
C. Vassalle, L. Petrozzi, N. Botto, M. G. Andreassi, and G. C. Zucchelli, “Oxidative stress and its association with coronary artery disease and different atherogenic risk factors,” Journal of Internal Medicine, vol. 256, no. 4, pp. 308–315, 2004.
N. Kuzkaya, N. Weissmann, D. G. Harrison, and S. Dikalov, “Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase,” The Journal of Biological Chemistry, vol. 278, no. 25, pp. 22546–22554, 2003.
A. D. Booth, S. Wallace, C. M. McEniery, J. Brown, D. R. W. Jayne, and I. B. Wilkinson, “Inflammation and arterial stiffness in systemic vasculitis: a model of vascular inflammation,” Arthritis and Rheumatism, vol. 50, no. 2, pp. 581–588, 2004.
K. M. M？ki-Pet？j？, F. C. Hall, A. D. Booth et al., “Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-α therapy,” Circulation, vol. 114, no. 11, pp. 1185–1192, 2006.
G. A. Woodard, V. G. Mehta, R. H. MacKey et al., “C-reactive protein is associated with aortic stiffness in a cohort of African American and white women transitioning through menopause,” Menopause, vol. 18, no. 12, pp. 1291–1297, 2011.
J. E. Manson, P. Greenland, A. Z. LaCroix et al., “Walking compared with vigorous exercise for the prevention of cardiovascular events in women,” The New England Journal of Medicine, vol. 347, no. 10, pp. 716–725, 2002.
S. Mora, N. Cook, J. E. Buring, P. M. Ridker, and I.-M. Lee, “Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms,” Circulation, vol. 116, no. 19, pp. 2110–2118, 2007.
H. Tanaka, C. A. DeSouza, and D. R. Seals, “Absence of age-related increase in central arterial stiffness in physically active women,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 1, pp. 127–132, 1998.
K. L. Moreau, K. M. Gavin, A. E. Plum, and D. R. Seals, “Oxidative stress explains differences in large elastic artery compliance between sedentary and habitually exercising postmenopausal women,” Menopause, vol. 13, no. 6, pp. 951–958, 2006.
T. Matsubara, A. Miyaki, N. Akazawa et al., “Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women,” The American Journal of Physiology: Heart and Circulatory Physiology, vol. 306, no. 3, pp. H348–H355, 2014.
K. Tanahashi, N. Akazawa, A. Miyaki et al., “Aerobic exercise training decreases plasma asymmetric dimethylarginine concentrations with increase in arterial compliance in postmenopausal women,” The American Journal of Hypertension, vol. 27, no. 3, pp. 415–421, 2014.
J. Sugawara, H. Inoue, K. Hayashi, T. Yokoi, and I. Kono, “Effect of low-intensity aerobic exercise training on arterial compliance in postmenopausal women,” Hypertension Research, vol. 27, no. 12, pp. 897–901, 2004.
I. Eskurza, L. A. Myerburgh, Z. D. Kahn, and D. R. Seals, “Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults,” The Journal of Physiology, vol. 568, no. 3, pp. 1057–1065, 2005.
C. A. DeSouza, L. F. Shapiro, C. M. Clevenger et al., “Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men,” Circulation, vol. 102, no. 12, pp. 1351–1357, 2000.
F. Franzoni, L. Ghiadoni, F. Galetta et al., “Physical activity, plasma antioxidant capacity, and endothelium-dependent vasodilation in young and older men,” The American Journal of Hypertension, vol. 18, no. 4, pp. 510–516, 2005.
G. L. Pierce, I. Eskurza, A. E. Walker, T. N. Fay, and D. R. Seals, “Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults,” Clinical Science, vol. 120, no. 1, pp. 13–23, 2011.
D. P. Casey, G. L. Pierce, K. S. Howe, M. C. Mering, and R. W. Braith, “Effect of resistance training on arterial wave reflection and brachial artery reactivity in normotensive postmenopausal women,” European Journal of Applied Physiology, vol. 100, no. 4, pp. 403–408, 2007.
B. A. Parker, M. J. Kalasky, and D. N. Proctor, “Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity,” European Journal of Applied Physiology, vol. 110, no. 2, pp. 235–246, 2010.
P. J. L. Ong, G. Patrizi, W. C. F. Chong, C. M. Webb, C. S. Hayward, and P. Collins, “Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease,” The American Journal of Cardiology, vol. 85, no. 2, pp. 269–272, 2000.
M. Tanasescu, M. F. Leitzmann, E. B. Rimm, W. C. Willett, M. J. Stampfer, and F. B. Hu, “Exercise type and intensity in relation to coronary heart disease in men,” Journal of the American Medical Association, vol. 288, no. 16, pp. 1994–2000, 2002.
A. K. Chomistek, N. R. Cook, A. J. Flint, and E. B. Rimm, “Vigorous-intensity leisure-time physical activity and risk of major chronic disease in men,” Medicine and Science in Sports and Exercise, vol. 44, no. 10, pp. 1898–1905, 2012.
C. A. D. Silva, J. P. Ribeiro, J. C. A. U. Canto et al., “High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus,” Diabetes Research and Clinical Practice, vol. 95, no. 2, pp. 237–245, 2012.
K. D. Currie, R. S. McKelvie, and M. J. MacDonald, “Flow-mediated dilation is acutely improved after high-intensity interval exercise,” Medicine and Science in Sports and Exercise, vol. 44, no. 11, pp. 2057–2064, 2012.
D. L. Swift, J. Y. Weltman, J. T. Patrie et al., “Predictors of improvement in endothelial function after exercise training in a diverse sample of postmenopausal women,” Journal of Women's Health (Larchmt), vol. 23, no. 3, pp. 260–266, 2014.
N. Yoshida, H. Ikeda, K. Sugi, and T. Imaizumi, “Impaired endothelium-dependent and -independent vasodilation in young female athletes with exercise-associated amenorrhea,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 1, pp. 231–232, 2006.
A. Rickenlund, M. J. Eriksson, K. Schenck-Gustafsson, and A. L. Hirschberg, “Oral contraceptives improve endothelial function in amenorrheic athletes,” The Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 6, pp. 3162–3167, 2005.
F. S. Gragasin, Y. Xu, I. A. Arenas, N. Kainth, and S. T. Davidge, “Estrogen reduces angiotensin II-induced nitric oxide synthase and NADPH oxidase expression in endothelial cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 1, pp. 38–44, 2003.