BERKELEY, CA (UroToday.com) - The clinical observation of unexpected deaths by acute stroke of men with cardiovascular disease (CVD) history and metastatic prostate cancer, treated with bilateral orchiectomy during the perioperational period, led the authors to investigate the association of low testosterone levels with stroke and sudden death. Existing evidence regarding the role of testosterone levels in the initiation of the ischemic cascade is generally poor. Observational studies showed that serum levels of total and free testosterone are inversely associated with stroke severity and 6-month mortality, while total testosterone was significantly inversely associated with infarct size,[1] and clinical studies showed that low free testosterone levels were related to intima-media thickening of the common carotid artery in elderly men, independently of cardiovascular risk factors.[2] The related pathophysiological mechanisms leading to these events remain unknown.
Actually, a critically important role of testosterone is to enable high-density lipoproteins to remove excess cholesterol from the arterial wall and transport it to the liver for disposal. This effect is termed “reverse cholesterol transport” and prevents the occlusion of arteries.[2] However, the low testosterone levels also promote platelet aggregation and coagulation. In a cross-sectional case-control study, exogenously administered testosterone upregulated platelet thromboxane A2 receptors and increased aggregation response to thromboxane mimetics in healthy male volunteers.[3]
Finally, the abrupt refraining of circulating testosterone leads to an imbalance between androgen and estrogen levels in favor of the latter. Increased estrogen levels in men may enhance rupture of unstable plaques, leading to coronary artery occlusion . With discontinuation of anticoagulation, despite bridging therapy with heparin, it seems that bilateral orchiectomy places patients with CVD history at greater risk. Given the minimal clinically important bleeding risks of the procedure, it is reasonable that patients undergoing bilateral orchiectomy should be adequately treated for post-operative stroke prevention. Further studies are warranted to determine the precise period of intense monitoring, the appropriate agent, and the duration of treatment.
References:
- Jeppesen LL, Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K. Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol. 1996;16(6):749-54.
- Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004;109(17):2074-9.
- Ajayi AA, Halushka PV. Castration reduces platelet thromboxane A2 receptor density and aggregability. QJM. 2005 May;98(5):349-56.
Written by:
Konstantinos Stamatiou as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Tzaneio General Hospital of Piraeus, Piraeus, Greece
More Information about Beyond the Abstract