Prostate-specific antigen (PSA) is a protein produced by cells in the prostate gland. PSA levels are often used as a screening test for prostate cancer. As men get older, their PSA levels tend to increase slowly over time. This article will examine whether PSA levels normally rise with age and discuss what higher PSA levels may indicate in older men.
What is PSA?
PSA is a glycoprotein enzyme encoded by the KLK3 gene in humans. It is produced by the epithelial cells lining the acini and ducts of the prostate gland. PSA acts to liquefy semen after ejaculation to allow sperm to swim freely. It helps break down the thick gel that gives semen its consistency.
PSA is also secreted into the bloodstream in small amounts. Measuring PSA levels in the blood can help screen men for prostate cancer or other prostate conditions. Higher than normal levels may indicate the presence of cancer or benign prostate hyperplasia (BPH).
Functions of PSA
The main functions of PSA include:
- Liquefying semen to allow sperm mobility
- Breaking down gel proteins in semen
- Serving as a growth factor for prostate cells
- Weak enzymatic protease activity in the blood that helps regulate insulin-like growth factors
In the prostate, PSA is involved in regulating prostate growth and development. In the bloodstream, it may play a role in regulating factors that influence cell proliferation.
Normal PSA Ranges
Normal PSA levels can vary somewhat based on age:
PSA Ranges by Age
| Age | Normal PSA Range (ng/mL) |
|---|---|
| 40-49 | 0-2.5 |
| 50-59 | 0-3.5 |
| 60-69 | 0-4.5 |
| 70-79 | 0-6.5 |
As the table shows, PSA levels below 4 ng/mL are generally considered normal for men in their 50s and 60s. However, up to 6.5 ng/mL can be considered normal for men in their 70s.
Some key things to note about normal PSA ranges:
- There is no specific “normal” level that applies to all men of all ages.
- PSA levels normally increase slowly as men get older.
- Black men tend to have higher PSA levels on average than white men.
For any individual, the most meaningful comparison is a baseline PSA level when they are young, which can be tracked over time. Sudden increases or high levels are more concerning than mild increases with age.
Does PSA Naturally Increase with Age?
Yes, PSA levels do indeed tend to rise as men get older, even if they do not have prostate cancer. The prostate gland tends to grow larger with age, a condition called benign prostatic hyperplasia (BPH). The prostate also becomes more permeable with age. These age-related changes cause more PSA to leak into the bloodstream and circulate at higher levels.
Some key reasons why PSA increases with age include:
Age-Related Prostatic Changes
- BPH: The prostate enlarges and accumulates more PSA-producing cells.
- Increased permeability: The aging prostate tissue becomes more “leaky,” releasing more PSA into the blood.
- Inflammation: Prostatitis can develop, leading to damaged cells that spill PSA.
- Cell turnover: The aging prostate has more cell damage and death, dumping PSA into circulation.
As the prostate increases in size and develops microscopic structural changes, more total PSA makes its way into the blood. This causes a gradual increase in measurable PSA levels.
However, PSA levels in an individual patient are also affected by:
- Genetics
- Environmental factors
- Medications
- Lifestyle habits
So while PSA tends to increase with age on average, individual PSA trajectories can vary significantly based on the patient’s unique characteristics.
Rate of PSA Increase by Age
Studies have found the following average rates of PSA increase with age in normal men without prostate cancer:
- Ages 40-49: PSA increases by an average of 0.04 ng/mL per year
- Ages 50-59: PSA increases by an average of 0.05 ng/mL per year
- Ages 60-69: PSA increases by an average of 0.07 ng/mL per year
The PSA increase tends to accelerate slightly in the 60s compared to the 40s and 50s. By the 70s, PSA velocity continues increasing another 0.02 ng/mL per year on average compared to the 60s.
However, keep in mind there is significant individual variation around these averages based on genetics, health status, and other factors.
Higher PSA with Age Can Indicate Cancer
While PSA normally rises as men age, a sharp increase or very high level can also be a sign of prostate cancer. Some key points about higher PSA levels in older men:
- PSA > 4 ng/mL has a 25% chance of cancer in men in their 60s.
- PSA > 10 ng/mL has a 67% chance of cancer in men in their 60s.
- High PSA levels indicate larger tumors that carry a higher risk.
- A PSA velocity > 0.35 ng/mL/year demands further evaluation.
- Sharp PSA spikes suggest the possibility of prostate cancer.
The higher a man’s PSA level and PSA velocity, the more likely it is that cancer is present. However, BPH can also cause elevated PSA in older men. Only a biopsy can definitively diagnose cancer.
Men over 60 should have an individualized approach to PSA screening based on their PSA trajectory, family history, overall health, and life expectancy. Those with a life expectancy of less than 10 years may avoid PSA testing, while it benefits those expected to live longer.
Evaluating Higher PSA in Older Men
When an older man has a higher-than-normal PSA level, doctors evaluate with additional tests:
- Free vs. bound PSA: Cancer is more likely if “free” PSA is low compared to bound PSA.
- PSA density: Compares PSA to prostate volume. Density > 0.15 suggests cancer.
- PSA velocity: Fast PSA rise indicates higher cancer risk.
- Age-specific PSA: Compares PSA to normal range for that age group.
- Prostate biopsy: Collecting tissue samples for pathology is the only way to definitively diagnose cancer.
Family history of prostate cancer also increases suspicions. Multiparametric MRI and molecular urine tests may help guide biopsy decisions.
Tips for Monitoring PSA with Age
Here are some tips for tracking PSA levels as you get older:
- Get a baseline PSA test in your 40s to determine your “normal.”
- Have annual PSA screening starting at age 50 if you have at least a 10-year life expectancy.
- Evaluate the rate of change rather than single PSA values.
- Expect PSA to rise 0.04-0.07 ng/mL yearly on average.
- Investigate further if your PSA velocity exceeds 0.35 ng/mL/year.
- Discuss a higher than expected PSA result with your doctor.
- Undergo regular screening if you have risk factors like African ancestry or family history.
- Repeat testing in 6-12 weeks if your PSA is borderline high before considering biopsy.
Tracking PSA numbers over time allows both you and your doctor to determine if your levels follow the normal gradual rise expected with aging versus a concerning rapid increase that demands evaluation.
The Takeaway
It is normal for PSA levels to gradually rise as men get older, even if cancer is not present. This age-related increase in PSA occurs because the prostate grows larger and becomes more permeable with aging. However, sharp PSA spikes or very high levels in older men can signal prostate cancer.
Have a baseline PSA test in your 40s for comparison over time. Routine screening should begin at 50 for those with a life expectancy of more than 10 years. Speak to your doctor about higher than normal PSA results to determine if additional testing is warranted. Monitor your PSA velocity in addition to the absolute number.
