Testosterone replacement therapy and anaemia in men with hypogonadism

Take-home points

• 2603 out of 5204 men with hypogonadism were given daily testosterone gel on their skin. 390 of these already had anaemia.
• Anaemia was significantly more likely to be corrected in the men using testosterone gel than using a placebo.
• The other 2213 men using the testosterone gel were less likely to develop anaemia than those using a placebo gel.
• All the included men had low testosterone and cardiovascular issues.
• More studies are needed into the role of testosterone replacement therapy and anaemia.

Testosterone replacement therapy and anaemia in men with hypogonadism

A new study in JAMA Network Open investigated the use of testosterone replacement gel to improve anaemia in men with hypogonadism.¹

What is anaemia?

It’s probably a condition you’ve heard of, and you might associate it with looking pale, fainting, and feeling tired. Anaemia is when the body doesn’t have enough healthy red blood cells to carry oxygen to the body's tissues. This might be because of an issue with the number of red blood cells, their shape/structure, or an issue with the components inside them that carry the oxygen.

There are different types of anaemia, and they’re caused by different things. Some common causes include poor diet (lacking iron and B12), blood loss, inflammation, and factors causing your body to not make enough red blood cells. Testosterone is one factor that helps increase the number of red cells produced naturally – low testosterone may lead to anaemia.

What is hypogonadism?

The term “hypogonadism” means that the gonads (the testicles or ovaries) are working less well than they should be. In men, this means the testicles aren’t producing enough testosterone and/or sperm.

There are different types of hypogonadism, depending on whether the problem is with the testicles themselves (primary hypogonadism) or an issue with the brain, affecting hormone production (secondary hypogonadism).

What is testosterone replacement therapy?

Testosterone replacement therapy (TRT) is when artificial testosterone is given to men with low testosterone levels. (It’s also given as a masculinizing hormone therapy to individuals transitioning.)  TRT can be taken as a tablet, injection, or applied to skin as a gel or patch.

Usually, the aim is to use TRT to return testosterone levels to within the normal range, and treat symptoms like low libido, low energy, loss of muscle mass, and hair loss. However, TRT can negatively affect sperm production and fertility.²

Study title:

• Efficacy of Testosterone Replacement Therapy in Correcting Anaemia in Men With Hypogonadism - A Randomized Clinical Trial

What did they do?

This study investigated the use of testosterone to improve, and prevent, anaemia in men with hypogonadism. It included 5204 men aged 45-80 years old with hypogonadism living in the United States. To be included, the men had to have two testosterone level results below 300 ng/dL.

2603 men were given testosterone gel, and 2603 were given a placebo gel to apply daily to their skin for up to 5 years. During this time, levels of various markers in their blood were measured.

At the start of the trial, 390 men in the testosterone gel group and 425 in placebo group had anaemia. Throughout the trial, doctors measured whether their anaemia improved. They also compared how many men with and without the testosterone gel developed anaemia.

What did they find?

First, let’s talk about the 815 men who already had anaemia. The anaemia improved (or resolved completely) in more men treated with the testosterone gel than the placebo. At six months, the anaemia was completely resolved in 33% of men using testosterone gel, but only 17% of men with the placebo gel – a significant difference (p=0.002).

For the men without anaemia, testosterone treatment was linked to a significantly reduced risk of developing anaemia. After 6 months, only 7% of men applying the testosterone developed anaemia compared to 10% of men applying the placebo (p=0.02).

What are the study conclusions?

The evidence from this trial suggests that testosterone gel can improve anaemia in men with hypogonadism. Using testosterone gel may also help prevent anaemia developing in men with hypogonadism.

How should we interpret this data?

These interesting findings suggest that testosterone replacement therapy can help treat and prevent anaemia in men with hypogonadism. It’s possible testosterone therapy could be used to improve anaemia in other men, but further studies are needed to confirm this. However, there are some limitations to the study that we need to think about.

All the included men had low testosterone to start with. Testosterone replacement therapy may not help improve anaemia in men with normal testosterone levels and hypogonadism. Whilst rare, some men with hypogonadism do have normal testosterone levels. The study findings don’t necessarily mean testosterone replacement therapy will improve anaemia in all men.

The men included in the study also had a cardiovascular disease* or risk factor**. This may have affected their risk of developing anaemia, and, again, may mean the findings don’t apply to other men with hypogonadism.

*Cardiovascular diseases include heart disease, a previous stroke, or disease of the arteries in the legs.

**Cardiovascular risk factors include things like high cholesterol, smoking, high blood pressure, age, and diabetes.

References

1. Pencina KM, et al. JAMA Netw Open 2023;6(10):e2340030.
2. Patel AS,et al. World J Mens Health 2019 Jan;37(1):45-54.