Gender-Specific Differences in the Effects of Testosterone and Estrogen on the Development of Atherosclerosis in Rabbits

Abstract

The aim of the present study was to investigate whether there are gender-specific differences in the effects of testosterone and estrogen on the process of atherogenesis. Thirty-two castrated male and 32 ovariectomized female rabbits were separated into 4 study groups of 8 males and 8 females each and received postoperatively a 0.5% cholesterol diet for 12 weeks. During this period either no hormones, estradiol (1 mg/kg body wt/week), testosterone (25 mg/kg body wt/week IMM), or estrogen combined with testosterone in above dosages were administered. Computerized morphometric analysis of the intimal thickening in the proximal aortic arch showed a significant inhibitory effect of estrogen in female and of testosterone in male animals (P < .05). In the group with combined treatment, the plaque size in both sexes was smaller than in the animals of the control group (P < .05). These differences were independent of changes in plasma lipid parameters. The incorporation of 5'-bromo-2'-deoxyuridine, associated with cell proliferation, into cells of the neointima was not significantly affected by the different hormone application regimens in males. In females, the incorporation rate was significantly lowered in the estrogen treated group compared with the control group (P < .05). Due to the observed differences in the sex specific atheroprotective effects of testosterone and estrogen, these data suggest that complex hormone interactions, which are independent of changes in plasma lipids, may play an important role in the process of atherogenesis.

Effect of Testosterone on Plaque Development and Androgen Receptor Expression in the Arterial Vessel Wall

“…Testosterone in male rabbits had an inhibitory effect on plaque development, but in female rabbits, an atheroprogressive action of testosterone was found. 2 These findings indirectly provide support for the hypothesis that arterial sex hormone receptors are probably involved as one part of the genomic actions of sex steroids on the level of the arterial vessel wall. 11 Androgen and estrogen receptors are present in vascular smooth muscle cells, 11,12 human macrophages, human megakaryocytes, and platelets.…”

“…Using data from previous animal studies, 2,3 it was postulated that genomic actions are involved in mediating the protective effects of testosterone in the process of atherosclerosis. We hypothesized that vascular androgen receptors might play an important role in signaling the testosterone effects on the level of the arterial vessel wall.…”

“…Animal studies have documented an inhibitory effect on plaque development in the cholesterol-fed rabbit model, 2,3 whereas in recent clinical investigations, acute hemodynamic effects of testosterone on coronary vasomotion and stress-test induced ischemia were observed. 4,5 Thus far, only limited information is available regarding the possible involvement of arterial androgen receptors in these processes.…”

Testosterone, SHBG and cardiovascular health in postmenopausal women

“…111,112 Results from experimental studies show a similar pattern. Bruck et al 113 showed an increase in plaque size after testosterone treatment in female rabbits on an atherogenic diet. This increase was independent of changes in plasma lipids.…”

Hormonal effects on blood vessels

“…[89][90][91] Effects of testosterone on animal models of atherosclerosis and neointima formation It has been demonstrated that the administration of testosterone in castrated male rabbits that were fed a high-cholesterol diet reduced aortic atherosclerosis, largely independent of plasma lipids. 92,93 In addition, neointima formation after coronary balloon injury in swine was increased by castration and was reversed by testosterone replacement. 94 Regarding the role of AR, conflicting findings have been reported.…”