Testosterone replacement therapy tends to lower HDL ("good") cholesterol slightly while also lowering total cholesterol and LDL ("bad") cholesterol, according to the largest meta-analyses on the subject (Whitsel et al., 2001; Isidori et al., 2005). The effect is generally small at normal treatment doses and has not been shown to translate into higher cardiovascular risk in randomized trials. Research on the topic is still mixed, and men starting TRT with existing cholesterol concerns should have their lipid panel checked before and periodically during treatment.
Does TRT Raise or Lower Cholesterol?
The honest answer is "it depends," and researchers themselves describe the evidence as inconsistent. Some studies find testosterone therapy modestly raises HDL, others find it lowers HDL, and at least one large cross-sectional analysis of NHANES data found no meaningful relationship between testosterone levels and total cholesterol at all (Gomes et al., 2023).
What is more consistent, particularly in older meta-analyses of injectable testosterone, is a pattern where TRT lowers HDL cholesterol by a modest amount while simultaneously lowering total cholesterol and LDL cholesterol (Whitsel et al., 2001). In other words, the full lipid picture tends to shift downward together, not just the "good" cholesterol in isolation.
Why Does TRT Lower HDL Cholesterol?
Testosterone affects an enzyme called hepatic lipase, which breaks down HDL particles in the liver. Higher androgen levels increase hepatic lipase activity, which can reduce circulating HDL concentrations (Thirumalai et al., 2017). This is a well-understood mechanism, but its clinical significance is where the research gets murkier.
Crucially, the size of the HDL drop is not fixed. It varies with dose, delivery method, and age:
- High-dose oral testosterone and anabolic steroid use in young men and athletes produce the largest, most concerning drops in HDL, sometimes 20 percent or more.
- Standard-dose transdermal or injectable TRT used to normalize testosterone in hypogonadal, middle-aged and older men has shown little to no effect on HDL in some studies (Thirumalai et al., 2017).
- Route of administration matters. Oral formulations that pass through the liver first ("first-pass metabolism") tend to affect lipids more than injections, pellets, or gels that bypass this process.
This is the key nuance most cholesterol-and-testosterone headlines miss: the doses and formulations that produced the scariest lipid numbers in older research are not the doses or formulations most TRT clinics prescribe today.
Is a Lower HDL on TRT Actually Dangerous?
This is where the research gets genuinely interesting. For decades, a low HDL number was treated as a straightforward red flag for heart disease. That assumption has weakened considerably.
The clearest example is the ILLUMINATE trial, which tested a drug called torcetrapib that raised HDL cholesterol by 72 percent, one of the largest HDL increases ever achieved pharmacologically, and yet the drug was still associated with more cardiovascular events, not fewer (Thirumalai et al., 2017). That result pushed researchers to question whether the total amount of HDL in the blood matters as much as how well those HDL particles actually function. Several major meta-analyses of testosterone therapy trials have found no association between TRT and cardiovascular events, despite the modest HDL changes observed in the underlying studies (Fernandez-Balsells et al., 2010; Corona et al., 2014).
The TRAVERSE trial, the largest randomized cardiovascular safety study of TRT to date with more than 5,000 men, found that testosterone therapy was noninferior to placebo for major adverse cardiovascular events (Lincoff et al., NEJM 2023). If modest HDL reductions from physiologic-dose TRT were driving meaningful cardiovascular harm, a trial of that size would have been positioned to detect it.
What About Triglycerides?
Triglycerides often move in the opposite direction from the HDL concern. Because TRT improves insulin sensitivity, reduces visceral fat, and builds lean muscle, many men see triglycerides fall as body composition improves on therapy, a pattern that mirrors what is seen with TRT and weight loss and TRT and diabetes more broadly. This metabolic improvement is one reason some researchers argue the net cardiovascular effect of correcting genuine hypogonadism is neutral to favorable, even when the HDL number alone ticks down slightly.
