Friday, September 23, 2011

Sympathetic Predominance: The link between erectile dysfunction, atherosclerosis and cardiovascular disease?

Erectile dysfunction affects 40% of men above 40 year old, in some degree, and two thirds of men over 70 have significant symptoms of ED.
The association between erectile dysfunction and coronary artery disease (CAD) was suggested years ago, by observational studies. More recently it was found that erectile dysfunction is an early marker of CAD, as the canary in the coal mine*.
Indeed some studies have demonstrated that coronary atherosclerosis is more severe in patients with vascular ED, with the authors considering that ED may be an additional, early warning sign of coronary atherosclerosis (1).
A recent meta-analysis of prospective cohort studies, involving 36,744 participants, have suggested that ED significantly increases the risk of cardiovascular disease, coronary heart disease, stroke, and all cause mortality, and the increase is probably independent of conventional risk factors (2)
Erection is initiated through the parasympathetic nervous system, activation of which overrides the sympathetic tone that maintains the penis in a nonerectile (flaccid) state. This state is maintained mainly through the release of norepinephrine from penile adrenergic nerves. Norepinephrine contracts the vasculature and cavernosal smooth muscle. Arousal/erection is associated with a decrease of norepinephrine release in the penis, with a release of nitric oxide, and with a reduction in penile smooth muscle tone. Thus, nitric oxide is a mediator of the parasympathetic vasodilation in erectile function (3). So, when the parasympathetic system is continuously disabled there is a reduced production of NO.
Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. ED is associated with smoking, excessive alcohol intake, abdominal obesity, diabetes, hypertension and decreased antioxidant defenses, all of which reduce NO production (4,). Recent studies have discussed about the benefits of lifestyle interventions like healthier eating habits, getting exercise and avoiding smoke for improving erectile dysfunction (5) and also targeting CAD risk factors reduction (4, 6).
It is interesting to note that ED and atherosclerosis have many risk factors in common like ageing, physical inactivity, improper diet, psychological stress, cigarette smoking, high blood pressure and diabetes. In relation to this point there are diverse studies showing that: a) increased sympathetic activity and mental stress may affect erectile function with studies suggesting that an elevated central sympathetic tone may be one of the causes of psychogenic impotence (7, 8, 9); b) a study suggested that drugs acting within the central nervous system that reduce the sympathetic antierectile flow and enhance the parasympathetic proerectile flow to the penis may restore penile erection in cases of erectile dysfunction of both psychogenic and organic origin (10); c) other study have demonstrated that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep (11); d) A study has shown that men with idiopathic ED have evidence of endothelial dysfunction in forearm resistance vessels, increased pulse pressure and impaired heart rate variability. According the authors this support the concept that erectile dysfunction is a predictor of cardiovascular dysfunction and a precursor of clinical cardiovascular disease (13). e) and, finally, a very recent study have shown that patients with ED exhibited different heart rate variability compared with normal controls. This suggested to the authors that the patients with ED may have some kind of imbalance in the autonomic nervous system (ANS) and it may be possible that general imbalance of the ANS is one of the causes of ED (12).
Taking in view the above studies and our postulation that sympathetic predominance is the primary factor in the cascade of events leading to the atherogenic spiraling (14, 15), we have to assume that it really is the link between ED and cardiovascular disease.
14. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
15. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at

Carlos Monteiro

*As long as the canary still singing, it is all ok. However, a dead canary is a warning of a larger problem.

1. Chiurlia E et al. Subclinical coronary artery atherosclerosis in patients with erectile dysfunction. J Am Coll Cardiol, 2005; 46:1503-6
2. Dong JY et al. Erectile dysfunction and risk of cardiovascular disease. Meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2011; 58:1378-1385
3. Andersson K, Stief C. Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms. Am J Cardiol. 2000 Jul 20;86(2A):23F-26F
4. Meldrum DR et al. The link between erectile and cardiovascular health: the canary in the coal mine. Am J Cardiol. 2011 Aug 15; 108(4): 599-606
5. Horasanli K et al. Do lifestyle changes work for improving erectile dysfunction? Asian J Androl, 2008; 10(1):28-35
6. Gupta PB et al. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: A systematic review and meta-analysis. Arch Intern Med, 2011. Published online September 12.
7. Junemann KP et al. Neurophysiological aspects of penile erection: the role of the sympathetic nervous system. Br J Urol, 1989 Jul;64(1):84-92
8. Pagani M. Hypertension, stress and erectile dysfunction: potential insights from the analysis of heart rate variability. Curr Med Res Opin, 2000; 16 Suppl1:s3-8
9. Diederichs W et al. The sympathetic role as an antagonist of erection. Urol Res. 1991;19(2):123-6
10. Allard J, Giuliano F. Central nervous system agents in the treatment of erectile dysfunction: how do they work? Curr Urol Rep 2001 Dec;2(6):488-94
11. Lavie P et al. Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction. J Sleep Res. 1999 Jun;8(2):135-42
12. Lee JY et al. Heart rate variability in men with erectile dysfunction. Int Neurourol J 2011;15:87-91. Full free text at
13. Stuckey BG, Walsh JP ET al. Erectile dysfunction predicts generalised cardiovascular disease. Evidence from a case control study. Atherosclerosis 2007, 194(2):458-6414.

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