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VOL. 50 N. 02, 2024 | International Brazilian Journal of Urology
intbrazjurol.com.br
119 | Do statins decrease testosterone in men? Systematic review and meta-analysis
Felipe Placco Araujo Glina, Leonardo Lopes, Rodrigo Spinola e Silva, Eduardo Augusto Correa Barros, Bruno Biselli, Sidney Glina [View Full Article]
ABSTRACT
Purpose
Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones.
Materials and Methods
Systematic Review with Meta-analysis, performed in Embase, Medline, and Cochrane databases, until May 2023; PROSPERO CRD42021270424 protocol. The selection was performed by two independent authors with subsequent conferences in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT), and cross-sectional studies (CSS)with a comparison of testosterone levels before and after statin administration and between groups. Bias analysis was evaluated with the Cochrane Tool, The Newcastle-Ottawa Scale(NOS), and using the Assess the Quality of Cross-sectional Studies (AXIS) tool.
Results
They were found on MedLine, Embase, and Cochrane, after selecting comparative studies, 10 CP and 6 RCT, and 6 CSS for the meta-analysis. In the Forrest plot with 6 CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02 ng/dL (95%CI=[39.40,70.64], I²=91%,p<0.00001). In the analysis with 5 RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12 ng/dL (95%CI=[1.16,25.08], I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06], I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal.
Conclusion
Statin use causes a decrease in total testosterone, not enough to cause a drop below the normal range, and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG, and Free Testosterone analysis.
INTRODUCTION
Statins are one of the most prescribed medications worldwide for lowering cholesterol. Therefore, they are efficient for the primary and secondary prevention of cardiovascular diseases (CVD) (1, 2). Because cholesterol is one of the precursors of adrenocortical and gonadal hormones, there is a concern that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors may impair testosterone production and other sex hormones (3, 4). This could lead eventually to hypogonadism in men. Defined as low levels of total serum testosterone (less than 300ng / dL) and free testosterone (less than 5 ng / dL)in combination with clinical symptoms such as low sex drive, fracture associated with osteoporosis and erectile dysfunction, or two or more of the following symptoms: sleep disturbances, depressed mood, lethargy, or decreased physical performance (5). The male hypogonadism can thus affect the function of multiple organs and the quality of life of patients.
*Due to the contradictory findings in the literature, the hypothesis of this study is that continuous use of statins may lead to decreased levels of testosterone and other sex hormones in patients with hypercholesterolemia, potentially resulting in hypogonadism. The primary objective is to assess whether continued use of statins in patients with hypercholesterolemia causes a decrease in testosterone levels. The secondary aim is to evaluate the hormonal axis, including free testosterone, estradiol, LH, FSH, and SHBG, with the chronic use of statins.
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