Explore how testosterone replacement therapy impacts PSA levels in men, based on two case studies. Learn its implications and future research directions.
Testosterone replacement therapy (TRT) combats symptoms like depression, reduced muscle strength, and decreased sexual desire due to old age or medical conditions. As a side effect, TRT can elevate prostate-specific antigen (PSA) levels, and although this increase is normal, it's crucial to monitor these changes diligently. We’ll find out why in this article.
Hypogonadism, TRT, and What to Expect
Hypogonadism is a medical term for decreased functional activity of the gonads, which can lead to testosterone deficiency. Men with hypogonadism tend to have lower PSA levels compared to men of the same age with normal testosterone levels. So, in a way, it's like their PSA levels are "on mute." 
When these men receive TRT, the situation can change, as an increase in testosterone naturally pulls up PSA levels. According to several investigations, men undergoing TRT tend to see an average increase of 0.30 ng/mL per year in their PSA levels. For older men, this increase can be even more significant, averaging around 0.43 ng/mL per year. It’s akin to TRT turning the volume back up on those PSA levels. 
It’s important to emphasize here that a change in PSA in itself isn't alarming; it's more about the rate of that change and how it might compare to the average. PSA is produced by both normal and malignant cells in the prostate, and an unexpected or rapid rise in PSA levels could indicate an inflammation of the prostate (prostatitis), an enlarged prostate (benign prostatic hyperplasia), or prostate cancer.
Case Scenario 1: How Testosterone Therapy Affects PSA Levels
In one particular research article, the researchers did a sort of study of studies—a systematic review and meta-analysis, to be precise. Think of it as collecting all the books in a library on a particular topic and then summarizing them to get a broader understanding. The main goal was to see how PSA levels changed before and after TRT and how many patients, if any, developed prostate cancer.
Using different sources, the researchers gathered studies that met the following criteria: studies that (1) were randomized controlled trials, which is considered the gold standard in medical research; (2) wherein the group being studied underwent testosterone therapy; (3) contained a control group that didn't receive any treatment; and (4) did not include men who have a history of prostate cancer.
According to the study, males who underwent testosterone therapy did, on average, have slightly higher PSA levels than men who did not receive the medication, although this difference was quite minuscule. On the other hand, the men who received the treatment via a shot in a muscle experienced a somewhat greater rise in PSA levels. However, neither the raised PSA levels nor the risk of developing prostate cancer differed significantly between the treatment and control groups. These findings imply that while testosterone therapy may induce spikes in PSA levels, these changes are minor and not always cause for alarm. 
It is important to have a Urologist monitor PSA levels while on TRT to confirm your health and safety. It is well known that men who present with low testosterone can have a higher risk of developing prostate cancer even when not undergoing TRT.
Case Scenario 2: Testosterone Therapy and Its Impact on Older Users
In another study, researchers conducted a double-blinded, placebo-controlled trial to find out how testosterone therapy affects older hypogonadal men. A placebo is a substance that has no therapeutic effect, similar to a sugar pill. In this form of study, neither the participant nor the researcher is aware of who is receiving the real treatment and who is receiving a placebo to rid the whole process of biases or other preconceived notions.
790 older males with low testosterone levels participated in this trial, which was conducted at 12 academic medical sites in the United States over 12 months. The study did not include men who had a high risk of developing prostate cancer. Some men received testosterone during the course of the study, while others received a placebo. The researchers then monitored changes in the men's PSA levels over this time.
The results demonstrated a small but statistically significant increase in PSA levels after treatment as compared to the placebo group. However, only 5% of males in the treatment group experienced this increase. Only a small percentage (2.5%) experienced a rise of more than 3.4 ng/mL, and an even smaller percentage (1.9%) had a verified absolute PSA of higher than 4.0 ng/mL. Four participants had prostate cancer, two of whom were diagnosed with a more aggressive form.
The researchers concluded from these findings that while testosterone treatment may induce a slight increase in PSA levels in older men with low testosterone, only a tiny number of men experience significant increases in PSA.
It is indeed vital to monitor PSA levels in men undergoing testosterone therapy, but it is likewise prudent to keep in mind that the likelihood of a significant increase is low. In light of these findings, it’s safe to say that the advantages of TRT frequently outweigh the risks, especially when patients are well-monitored by a Urologist who understands PSA kinetics while on TRT. 
The cases shown above provide important insights into the link between TRT and PSA levels. Perhaps most crucially, they provide some reassurance that testosterone therapy often does not result in significant rises in PSA levels, a marker frequently associated with prostate cancer. Having said that, these findings highlight the importance of closely monitoring PSA levels in males taking testosterone therapy, particularly among older men and those receiving intramuscular injections.
While these studies contribute to a better understanding of the association between testosterone therapy and PSA levels, there is still much more to learn. The long-term consequences of TRT on PSA levels and prostate health must be thoroughly investigated, as must alternative methods of providing TRT that limit PSA increases.
Do you want to learn more about the effects of TRT on your health? Are you concerned about your prostate health or PSA levels while on TRT? REGENX Health gives energy and performance medicine insights as well as personalized expert recommendations for men. Visit our website today to learn more about how we can help you enhance your health and performance.