Statins, LDL-C, and Testosterone

My primary care doctor has repeatedly stated a concern that reducing LDL-C via statins or other interventions could impact testosterone production. My understanding is that circulating LDL-C is not necessary for testosterone synthesis, and my guess is that any link between low LDL-C and low testosterone is a post hoc ergo propter hoc fallacy (where both low levels have a common cause), but I haven’t found good evidence to make that case or convince myself I am wrong. Anybody know about this?


Not sure how much credence to give to the Claude LLM on this, but it tracks:

Is there any evidence relating LDL-C as a cause of testosterone level as opposed to a correlation at the low end that might be the result of a common cause?

There is limited direct evidence linking LDL cholesterol (LDL-C) levels as a causal factor for testosterone levels. Most of the available research suggests an association or correlation between lower LDL-C levels and lower testosterone levels, but the nature of the relationship and the direction of causality are not entirely clear.

Here’s a summary of the relevant evidence:

  1. Observational studies: Several observational studies have found an association between lower LDL-C levels and lower testosterone levels in men. For example, a study published in the Journal of Clinical Endocrinology and Metabolism in 2008 found that men with lower LDL-C levels had lower testosterone levels, even after adjusting for age, body mass index (BMI), and other factors.

  2. Mechanism of action: While the exact mechanism is not fully understood, it has been suggested that cholesterol is a precursor for steroid hormone synthesis, including testosterone. Lower levels of cholesterol, including LDL-C, may limit the availability of precursors for testosterone production.

  3. Genetic studies: Some genetic studies have looked at the relationship between genetic variants associated with LDL-C levels and testosterone levels. A study published in the Journal of Clinical Endocrinology and Metabolism in 2018 found that genetic variants associated with lower LDL-C levels were also associated with lower testosterone levels in men.

However, it’s important to note that these studies do not prove a direct causal relationship between LDL-C and testosterone levels. The observed association could be due to a common underlying factor or mechanism affecting both LDL-C and testosterone levels.

For example, obesity, insulin resistance, and other metabolic disorders are known to influence both lipid profiles (including LDL-C levels) and testosterone production. Therefore, it’s possible that the association between low LDL-C and low testosterone levels is a consequence of a shared underlying factor, rather than LDL-C being a direct cause of low testosterone levels.

To establish a causal relationship, interventional studies would be needed, where LDL-C levels are deliberately manipulated (e.g., through dietary or pharmacological interventions), and the resulting effects on testosterone levels are observed. However, such interventional studies are limited, and the existing evidence is primarily based on observational and genetic association studies.

In summary, while there is an observed association between lower LDL-C levels and lower testosterone levels in men, the available evidence does not conclusively establish LDL-C as a direct cause of lower testosterone levels. The relationship may be a result of shared underlying factors or mechanisms affecting both lipid metabolism and testosterone production.