| ObjectiveTo investigate the effects of lipid-lowering therapy with different dose of Simvastatin on serum testosterone, estradiol, FSH, LH in S-D male rats.Subjects and methodsTotally 40 S-D male rats, weighted 308.3±13.4g and aged 8w and bought from the Beijing Weitonglihua Animal Experimental Centre, were employed to undergo this experiment.The 40 rats were equally randomized into 4 groups. A dose of 4mg/kg.d of Simvastatin is given in group A while 8mg/kg.d in group B while 16mg/kg.d in group C and no Simvastatin in group D.The levels of serum LDL-C,testosterone,estradiol, FSH, LH at the baseline and the 40w of the treatment. To avoid the inaccuracy of hormones levels caused by the physiological fluctuations in different times of day, morning fasting blood samples were collected from the subclavian vein. Amount of 3ml blood sample was centrifug in 3000rpm for 15min to obtain the supernatant. Enzymatic oxidation was used to detect LDL-C level while RIA was employed to measure the levels of testosterone, estradiol, FSH and LH. Comparison of statistical methods using balanced ANOVA test, P<0.05 was considered statistically significant.ResultsThere were no statistically significant increases in body weight or composition in response to the Simvastatin. Fasting blood glucose was significantly elevated in rats fed the Simvastatin for 40 weeks between groups, which were between 3.94 and 4.37 mmol per liter at baseline, had changed at 40 weeks to 6.88,6.59,8.45 mmol per liter in the 4mg,8mg, and 16mg Simvastatin groups, respectively.Levels of serum LDL cholesterol at week 40 were reduced from mean baseline levels, which were between 0.43 and 0.47 mmol per liter, to 0.44,0.27,0.25, and 0.18 mmol per liter.Similarly, at week 40, reductions in levels of total cholesterol from mean baseline levels (between 2.11 and 2.24 mmol per liter) were 1.79,1,29 and 0.75 mmol per liter (mean reductions from baseline,20%,39%, and 64%) in the low-dose, medium-dose, and high-dose Simvastatin groups, respectively. Levels of serum triglycerides, which were between 0.71 and 0.74 mmol per liter at baseline, had changed at 40 weeks to 0.79,0.53,0.48, and 0.41 mmol per liter in the placebo group and the 4mg,8mg, and 16mg Simvastatin groups (mean changes from baseline,8%,-27%,-32%, and-43%), respectively.Levels of serum AST and ALT increased with the addition of Simvastatin; the baseline values were between 160 and 178 u per liter and the values at 40 weeks were 210,259 and 262 u per deciliter in the low-dose, medium-dose, and high-dose Simvastatin groups, respectively, there were similar reductions among the four groups in ALT levels, the baseline values were between 38 and 46 u per liter and the values at 40 weeks were 62,71 and 80 u per liter.Modest changes in levels of serum HDL cholesterol were observed at 40 weeks:0.13,0.25,0.18, and 0.15 mmol per liter in the placebo group and the groups that received 4mg,8m μg, and 16mg of Simvastatin, respectively.Decreases in testosterone lever by simvastatin adminstration were observed in the 4mg(146.1±23.74nmol per liter, P>0.05),8mg(117.3±40.85nmol per liter, P>0.05), and 16mg (64.75±24.96nmol per liter,P<0.001)Simvastatin groups. The decrease in testosterone lever was clearly lower in the 16mg(64.75±24.96nmol per liter,P< 0.001) group than in the control group(227.5±28.98nmol per liter).Decreases in estradiol lever by simvastatin adminstration were observed in the 4mg(1.340±0.06351pmol per liter, P>0.05),8mg(1.163±0.1285pmol per liter, P>0.05), and 16mg(0.9600±0.1308pmol per liter,P<0.05) Simvastatin groups. The decrease in estradiol lever was clearly lower in the 4mg(P<0.001),8mg(P<0.001) and 16mg(P< 0.001) group than in the control group(2.117±0.1146pmol per liter).Decreases in progesterone lever by simvastatin adminstration were observed in the 4mg(1.733±0.3603nmol per liter, P>0.05),8mg(1.940±0.4627nmol per liter, P>0.05), and 16mg(0.745±0.2814nmol per liter,P>0.05) Simvastatin groups. The decrease in progesterone lever was clearly lower in the 4mg(P< 0.05),8mg(P< 0.01) and 16mg(P< 0.001) group than in the control group(4.423±0.5101nmol per liter).Increases in FSH lever by simvastatin adminstration were observed in the 4mg(3.623±0.5626μg per liter, P<0.05),8mg(5.937±0.2753μg per liter, P<0.001), and 16mg(7.323±0.1971μg per liter,P<0.0001) Simvastatin groups. The increase in FSH lever was clearly higher in the 4mg(P< 0.01),8mg(P<0.0001) and 16mg(P<0.0001) group than in the control group(1.418±0.1886μg per liter).Increases in FSH lever by simvastatin adminstration were observed in the 4mg(6.747±0.3459μg per liter, P>0.05),8mg(7.453±0.4883μg per liter, P<0.05), and 16mg(8.655±0.4928μg per liter,P<0.01) Simvastatin groups. The increase in LH lever was clearly higher in the 16mg(P<0.05) group than in the control group(5.693±0.7993μg per liter).ConclusionsIntensive lipid-lowering therapy with high dose Simvastain may decrease the testosterone,estrogen and estrogen level in male rats. |
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