I want to introduce you to something in the prostate gland that you probably never heard of. It’s a molecular compound called spermine. If you immediately think of sperm, you’re not far off. In fact, this compound was first discovered in semen. It plays an important part in successful fertility.

When deposited in a woman’s vagina, sperm begin racing to find their goal, a woman’s ovum (egg). Their journey is not easy. As one article puts it, “sperm navigate through a series of intricate pathways and face numerous obstacles.” Out of the 100 million or so sperm released when a man ejaculates, most get lost, trapped, or deteriorate out of sheer weariness before reaching their destination. This is where spermine comes in.

For an individual sperm, spermine is like a health supplement you might take in hopes of living longer and stronger. It stabilizes and protects the outer wrapper, or membrane, of the sperm cell carrying its precious cargo of genes needed to merge with those in the egg. The fraction of sperm lucky enough to make it as far as the egg are those with the sturdiest membrane plus the most stamina. Spermine is what helps equip them to meet their goal.

What does this have to do with prostate cancer?

As it turns out, spermine isn’t confined just to sperm. It is generally present in the male reproductive system, including the prostate gland. In fact, the prostate has the highest concentration of spermine in the human body. But, here’s a curious fact: When prostate cancer (PCa) is present, the concentration of spermine in tumor tissue drops, lowering the level of spermine in the gland itself.

More importantly, spermine also shows up in a man’s urine, because urine picks up spermine as it passes through the prostate gland on its way from the bladder to the penis. Studies show that in men with PCa, their urine samples will have less spermine compared to healthy men. This measurement is called urine spermine. Low urine spermine levels are now thought to be a kind of biomarker for PCa.

Two important studies

For background purposes, here’s an important study. In 2021, the prestigious journal Nature published a research analysis of 600 men whose PSA tests were suspicious (PSA 4-20 ng/ml). Before biopsy their urine was analyzed for spermine levels, and the results were correlated with their biopsies. When spermine levels were combined with each patient’s PSA, age, prostate volume, and digital rectal exam for a total Spermine Risk Score, the results were 90% predictive of high grade PCa as shown on biopsy. The Spermine Risk Score was also 95% accurate in predicting the absence of high grade PCa. According to this study’s findings, “36.7% biopsies and 24.4% ISUP grade group 1 diagnoses could have been avoided.”^[i]

A more recent study connects urine spermine with something we specialize in at our Sperling Prostate Center, multiparametric MRI (mpMRI). An Asian research team hypothesized that adding mpMRI with its PI-RADS scores to the Spermine Risk Score, as described above, would further improve PCa prediction and identify which patients could avoid a biopsy. The team conducted an analysis of 265 cases of men suspected of PCa based on their PSA results. The results showed that including mpMRI in the Urine Spermine Risk Score accurately identified men at high risk of high grade PCa while reducing unnecessary biopsies.^[ii]

Experts in the field are increasingly convinced that there is an important role for urine spermine in differentiating who does or does not need a biopsy following a suspicious PSA. The addition of mpMRI into the Spermine Risk Score makes it clearer than ever that annual PSA blood tests should not be avoided out of concern that a man will be rushed to biopsy. Following a suspicious PSA with a measurement of urine spermine and mpMRI is such a simple way to determine who does or does not need a biopsy. If noninvasive biomarkers and imaging can be made widely available, it will enhance the process of early PCa detection. As I’ve pointed out many times, early detection not only saves lives; by catching PCa when a focal therapy like Focal Laser Ablation or TULSA is appropriate, it also saves lifestyles.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Chiu, P.KF., Fung, YH., Teoh, J.YC. et al. Urine spermine and multivariable Spermine Risk Score predict high-grade prostate cancer. Prostate Cancer Prostatic Dis 24, 542–548 (2021).
[ii] Isotani S, Ka-Fung Chiu P, Ashizawa T, Fung YH et al. Urine spermine and multiparametric magnetic resonance imaging for prediction of prostate cancer in Japanese men. Prostate Int. 2023 Sep;11(3):180-185.