PSA Variability: A new factor
Harvard Men’s Health Watch Publications
Volume 12 – Number 8 March 15, 2008

It’s a simple question, but for many men who choose to have the prostate-specific antigen blood test to screen for prostate cancer, there is no simple answer. That’s because PSA levels, like other biological functions, often vary. Since all prostate cells, both benign and malignant, produce the controversial protein, in most cases the swings have nothing to do with prostate cancer. And a new study sheds surprising light on a previously unsuspected reason for PSA variability.

RAPID CHANGES

Short-term variations in the PSA are well-known. Inflammation of the prostate (prostatitis) and urinary tract infections boost the PSA rapidly, often to very high levels. The same is true for medical manipulations that affect the gland, including prostate biopsies and the placement of a Foley catheter in the bladder. A doctor’s digital rectal exam (DRE) is a low-tech medical manipulation; some studies suggest that DREs can temporarily elevate blood PSA levels, while others do not.

A man’s behavior can also produce short-term changed in his PSA. For example, putting the prostate to work can nudge up PSA readings; when ejaculation elevates PSA results, the effect less than 48 hours, which is why many doctors recommend a few days of abstinence before a blood sample is obtained for testing. Similarly, a vigorous workout on an exercise bike may produce a temporary PSA bump.

Technical factors may also explain short-term PSA variability. Even the best of labs may report different results when they test the same blood sample twice, but these differences are usually quite small. However, if different PSA testing methods are used by different labs, larger disparities can occur.

SLOW CHANGES

Long-term variation in PSA results is also common. The most important factor is age; over time, many men develop benign prostatic hyperplasia (BPH), and as the prostate enlarges, the PSA rises. Men who take finasteride (Proscar) or dutasteride (Avodart) to treat BPH typically experience about a 50% drop in their PSA values as t heir prostates shrink. In contrast, testosterone therapy can be expected to increase PSA levels as prostate cells enlarge.

UNEXPLAINED CHANGES

In addition to change that can be traced to specific causes, changes in the PSA can develop without evident explanation. For example, a 2005 analysis of 12 earlier studies found that repeat PSA tests vary about 20% in men older than 50. Similarly, a study of 972 men who each had five PSA tests during a four-year period revealed that a high proportion of men who had an abnormally high PSA result on one test had a normal PSA result on one or more subsequent test. In addition, a study of 295 men who had two PSA tests within 90 days found that consecutive results varied by more than 1.0 nanograms per milliliter (ng/mL) in one-third of the men.

When a man’s PSA reading seems to rise, the patient and his doctor should think about all the possible reasons for the change. And a report from Europe offers yet another possible explanation for varying PSA levels.

THE NEW STUDY

From the Nobel Peace Prize to presidential politics, climate change is big news. But even Al Gore might be surprised that climate can affect a man’s PSA.

The study cracked PSA reading in 8,644 men who were enrolled in the European Randomized Study of Screening for Prostate Cancer (ERSPC). The participants were between the ages of 55 and 70, and they lived in two regions of France, one rural and the other partially urban. Detailed meteorologic data were available for both regions, allowing the researchers to evaluate the effect of climate on PSA levels.

Both regions have temperate climates, and in both, PSA levels held steady in autumn, winter, and spring. But summer was a different story: total PSA levels averaged about 0.5 ng/mL higher in summer than in any other season. That amounts to a 20% seasonal rise in PSA, enough to increase a man’s likelihood of being sent for a prostate biopsy by 23%.

Although the French scientists are not sure how climate affects blood PSA levels, they believe that exposure to sunlight is more important than temperature. As a result, they speculate that a seasonal increase in vitamin D could influence the activity of prostate cells. Since prostate tissue binds melatonin as well as vitamin D, lower summertime levels of the “dark hormone” that helps regulate sleep could be another factor.

Other possible explanations include summertime increases in testosterone levels or sexual activity. Warmer temperatures and increased outdoor exercise might also produce some degree of dehydration, which could affect blood tests.

More research is needed to confirm the ERSPC study results and to investigate how climate affects the prostate. It may not be a hot topic for scientists, but it could be important for men whose PSA results swing up in summer.

INCONVENIENT TRUTHS – about the PSA

PSA testing is one of the most important – and controversial – issues in men’s health. Doctors know that PSA testing is the best available way to detect early prostate cancer, but they don’t know if early diagnosis will lead to better outcomes. More than that, scientists disagree about what levels of PSA should be considered abnormal, triggering referral for a prostate biopsy. And with all the nonmalignant factors that can boost a man’s PSA, it’s hard to be sure if a single reading is the “real” result.

Amidst this uncertainty, one fact is clear: a man’s response to a high or rising PSA reading should not be panic. Instead, he should think about all the things that can affect his result; according to the ERSPC study, having the test switches from another time of year to the summer now belongs on the list. And after considering the many factors that can change his PSA, a man’s next response is also clear: get a repeat test before going any further.