The Prostate-Specific Antigen (PSA) blood test is a common screening tool for prostate health concerns. A high result often causes immediate worry about prostate cancer. However, the prostate gland naturally increases in size as men age. This normal aging process can lead to an elevated PSA result, suggesting that a high reading is not automatically an indication of serious illness.
What PSA is and How Prostate Enlargement Occurs
Prostate-Specific Antigen (PSA) is a protein produced primarily by the epithelial cells within the prostate gland. Its main function is to help liquefy semen, allowing sperm to swim more freely after ejaculation. Although PSA’s primary role is within the seminal fluid, a small amount always leaks into the bloodstream, where it can be measured with a blood test.
Prostate enlargement is officially termed Benign Prostatic Hyperplasia (BPH). This non-cancerous condition affects most men as they grow older; by age 80, most men show evidence of this growth. BPH is characterized by the proliferation of glandular and stromal cells, mainly in the transitional zone of the prostate surrounding the urethra. This growth is driven by age-related changes in hormone levels, specifically prolonged exposure to dihydrotestosterone (DHT).
The Direct Link Between BPH and PSA Elevation
An enlarged prostate directly causes an increase in the total amount of PSA produced because there are more cells generating the protein. As the prostate volume increases due to BPH, the overall output of PSA rises proportionally, even if individual cells are not producing an abnormal amount. This mechanism explains why a high PSA level can be a benign finding.
The increased volume also changes the gland’s internal structure, allowing more PSA to leak from the prostate tissue into the bloodstream. While BPH leads to a measurable elevation in PSA, this rise is usually steady and moderate over time. Physicians often account for this effect by calculating the PSA density, which divides the total PSA value by the prostate volume, to better evaluate the reading’s significance.
Other Medical Conditions That Raise PSA Levels
BPH is a common cause of PSA elevation, but other non-cancerous conditions can also raise the level. Inflammation or infection of the prostate, known as prostatitis, causes a significant, often temporary, spike in PSA. This condition irritates the prostate tissue, increasing the permeability between the gland and the bloodstream, leading to a surge in circulating PSA. Urinary tract infections (UTIs) can also cause a temporary rise due to associated inflammation.
Prostate cancer cells produce PSA, often generating a much higher amount of the protein per cell compared to benign cells. This leads to a more rapid and significant rise in the overall PSA level. Therefore, a rapidly increasing PSA over serial tests, known as PSA velocity, is viewed with greater suspicion than a stable, moderately elevated level.
External factors can artificially inflate the PSA reading, requiring a retest to confirm the true baseline level. Patients are typically advised to avoid certain activities for 48 hours or more before having their blood drawn. These activities include:
- Recent ejaculation
- Vigorous exercise like long-distance cycling
- Any procedure that manipulates the prostate, such as a digital rectal exam (DRE) or a biopsy
Interpreting High PSA Results and Next Steps
Interpreting a high PSA reading requires a comprehensive approach, as the elevation can be caused by BPH, infection, or cancer. The physician usually begins with a Digital Rectal Exam (DRE) to feel the prostate’s size, shape, and texture, looking for suspicious lumps or hard areas. If the initial reading is elevated, the doctor may order a repeat PSA test after a few weeks to rule out temporary factors like a subclinical infection or recent activity.
A valuable tool for differentiation is the Free PSA Ratio, which measures the percentage of unattached PSA versus the total PSA in the bloodstream. In men with BPH, a higher proportion of PSA circulates freely. Conversely, a lower percentage of free PSA (especially below 10-25%) is often associated with a greater risk of prostate cancer. The combination of a persistently elevated PSA, a low free PSA ratio, or a suspicious DRE finding often leads to advanced imaging, such as an MRI, followed by a prostate biopsy.