This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Komesaroff, P. A. Articles by Sudhir, K. Search for Related Content PubMed PubMed Citation Articles by Komesaroff, P. A. Articles by Sudhir, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Clinical Studies

(Hypertension. 2001;38:1011.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Low-Dose Estrogen Supplementation Improves Vascular Function in Hypogonadal Men

Paul A. Komesaroff; Meryl Fullerton; Murray D. Esler; Anthony Dart; Garry Jennings; Krishnankutty Sudhir

From the Hormones and Vasculature Laboratory and Alfred and Baker Medical Unit, Baker Medical Research Institute and Alfred Hospital, Melbourne, Victoria, Australia.

Correspondence to Dr K. Sudhir, Alfred Heart Center, 3rd Floor, Alfred Hospital, Commercial Rd, Prahran, VIC 3181, Australia. E-mail k.sudhir{at}alfred.org.au

Abstract—— It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean±SEM age, 68.7±2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308±65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N^G-monomethyl-L-arginine (1, 2, 4 µmol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 µg/min) or to the endothelium-independent agent sodium nitroprusside (1.6 µg/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.

Key Words: estrogen • men • vascular diseases • hypogonadism • nitric oxide • norepinephrine • angiotensin II • stress

This article has been cited by other articles:

				E. A. Jankowska, P. Rozentryt, B. Ponikowska, O. Hartmann, D. Kustrzycka-Kratochwil, K. Reczuch, J. Nowak, L. Borodulin-Nadzieja, L. Polonski, W. Banasiak, et al. Circulating Estradiol and Mortality in Men With Systolic Chronic Heart Failure JAMA, May 13, 2009; 301(18): 1892 - 1901. [Abstract] [Full Text] [PDF]

				G. Douglas, M. Natalia Cruz, L. Poston, J.-A. Gustafsson, and K. Kublickiene Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor- knockout mouse Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R112 - R120. [Abstract] [Full Text] [PDF]

				H. R. N. Pour, D. E Grobbee, M. Muller, M. Emmelot-Vonk, and Y. T van der Schouw Serum sex hormone and plasma homocysteine levels in middle-aged and elderly men Eur. J. Endocrinol., December 1, 2006; 155(6): 887 - 893. [Abstract] [Full Text] [PDF]

				J. Arnlov, M. J. Pencina, S. Amin, B.-H. Nam, E. J. Benjamin, J. M. Murabito, T. J. Wang, P. E. Knapp, R. B. D'Agostino Sr., S. Bhasin, et al. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med, August 1, 2006; 145(3): 176 - 184. [Abstract] [Full Text] [PDF]

				K. K. Koh, M.-S. Shin, I. Sakuma, J. Y. Ahn, D. K. Jin, H. S. Kim, D. S. Kim, S. H. Han, W.-J. Chung, and E. K. Shin Effects of Conventional or Lower Doses of Hormone Replacement Therapy in Postmenopausal Women Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1516 - 1521. [Abstract] [Full Text] [PDF]

				M. E. Mendelsohn and G. M.C. Rosano Hormonal Regulation of Normal Vascular Tone in Males Circ. Res., December 12, 2003; 93(12): 1142 - 1145. [Full Text] [PDF]

				M. Kimura, K. Sudhir, M. Jones, E. Simpson, A.-M. Jefferis, and J. P.F. Chin-Dusting Impaired Acetylcholine-Induced Release of Nitric Oxide in the Aorta of Male Aromatase-Knockout Mice: Regulation of Nitric Oxide Production by Endogenous Sex Hormones in Males Circ. Res., December 12, 2003; 93(12): 1267 - 1271. [Abstract] [Full Text] [PDF]

				R. Lew, P. Komesaroff, M. Williams, T. Dawood, and K. Sudhir Endogenous Estrogens Influence Endothelial Function in Young Men Circ. Res., November 28, 2003; 93(11): 1127 - 1133. [Abstract] [Full Text] [PDF]

				P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]