For years, testosterone has played the role of both villain and hero in the story of prostate cancer treatment. Traditionally, blocking testosterone—the hormone that fuels prostate cancer growth—has been the gold standard for slowing tumor progression in early-stage disease. Yet in a surprising twist, doctors have found that increasing testosterone levels in men with advanced prostate cancer can actually slow the disease down.
This strange contradiction has puzzled researchers and created a roadblock in developing new, more effective therapies.
But now, a groundbreaking study led by the Duke Cancer Institute, published in Nature Communications, may have finally unraveled this mystery.
The Puzzle: How Can the Same Hormone Have Opposite Effects?
Dr. Donald McDonnell and his team at Duke University took a deep dive into the molecular workings of prostate cancer cells. They discovered that these cells have an internal mechanism allowing them to thrive when testosterone is scarce. In this low-hormone environment, cancer cells activate growth and survival pathways using androgen receptors—the cellular sensors that respond to testosterone.
But here’s the twist: when testosterone levels are brought back to normal or high levels, the androgen receptors behave differently. Instead of promoting cancer growth, they pair up and signal the cells to differentiate—essentially pushing them to stop multiplying and behave more like normal prostate cells.
Why This Matters
According to lead author Dr. Rachid Safi, this mechanism helps explain the success of a newer treatment approach called bipolar androgen therapy (BAT). This therapy involves giving patients with advanced prostate cancer high doses of testosterone at regular intervals.
“Nature has designed a system where low doses of hormones stimulate cancer cell proliferation, and high doses suppress it,” said Dr. McDonnell. This duality allows the same hormone to produce completely different effects depending on its concentration in the body.
New Hope for Advanced Prostate Cancer
Endocrine therapy—blocking androgen receptors—has long been effective, especially in the early stages of prostate cancer. But most men with advanced or therapy-resistant prostate cancer eventually see the disease progress. At that point, treatment options become extremely limited.
That’s where BAT and similar hormone-based strategies may offer a lifeline.
The Duke team’s findings not only explain why these treatments work, but they’re also leading to the development of new drugs that target the same pathways, with the potential to treat advanced prostate cancer more effectively.
What’s Next?
These insights could help doctors identify which patients are most likely to benefit from therapies like BAT. Clinical trials are already underway, and researchers are optimistic about translating these lab discoveries into real-world results.
As the science catches up with the clinic, patients battling advanced prostate cancer may soon have more options—and a better understanding of how testosterone can be both a friend and a foe.
